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GOOD MORNING, EVERYONE.

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WELCOME AGAIN TO THE SIXTH

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BIENNIAL HIV/AIDS CURE MEETING.

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WE'RE GOING TO START OFF THIS

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MORNING, IT'S GOING TO BE TH SAA

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BRIDGES.

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>> GOOD MORNING, EVERYONE.

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I'M SANDRA BRIDGES, PROGRAM

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OFFICER ALONG WITH ERIC FOR THE

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REACH COLLABORATORY, AND I THINK

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AS YOU CAN SEE ON THE SCREEN,

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THAT STANDS FOR RESEARCH

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ENTERPRISE TO ADVANCE A CURE FOR

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HIV.

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I'VE ASKED THEM FOR A SHORTER

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NAME BUT THAT'S IT.

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THIS IS REACH.

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WE HAVE TWO -- WE HAVE CO-PIs

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ON THIS COLLABORATORY.

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THEY ARE BRAD JONES, WHO'S BASED

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AT WEILL CORNELL MEDICINE, AND

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MARINA CASKEY, WHO'S AT THE

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ROCKEFELLER.

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SO I THINK AT THIS POINT, I'LL

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TURN IT OVER TO BRAD, AND HE'LL

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CARRY ON.

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THANK YOU.

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IT'S A PLEASURE TO INTRODUCE THE

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GROUP.

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>> THANKS SO MUCH, SANDRA,
AND

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ERIC, FOR BEING SUCH SUPPORTIVE

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PROGRAM OFFICERS.

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IT'S MY PLEASURE TO GIVE THIS

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OVERVIEW FOR REACH AND SEE IF I

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CAN ADVANCE MY SLIDES ALSO.

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SO AS SANDRA MENTIONED I CO-LEAD

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THIS PROGRAM WITH MARINA CASKEY

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AS WELL AS ADAM WARD.

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THIS IS OUR EXECUTIVE COMMITTEE,

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THEY SERVE A NUMBER OF IMPORTANT

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ROLES.

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WE'RE CHARGED WITH DYNAMICALLY

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TRYING TO ALLOCATE RESOURCES TO

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SUPPORT THE HIGHEST PRIORITY

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SCIENCE AND WE DO THAT WITH THE

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DISCUSSION AND VOTES OF OUR

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EXECUTIVE COMMITTEE MEMBERS.

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SO REACH IS LARGELY AN IMMUNE

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BASED COLLABORATORY, WE'RE

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TRYING TO HARNESS THE IMMUNE

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SYSTEM TO CURE HIV OR ACHIEVE

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REMISSION.

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WE'RE MOSTLY FOCUSED ON

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CD8 T-CELLS AND NATURAL KILLER

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CELLS.

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WE LOOK AT RESERVOIR DYNAMICS

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AND HOW THESE RELATE TO T-CELL

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RESPONSES, HOW T-CELLS CAN SHAPE

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THE RESERVOIR EVEN UNDER

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ANTIRETROVIRAL THERAPY.

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WE HAVE A MAJOR FOCUS ON

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UNDERSTUDIED POPULATIONS, IN

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PARTICULAR A FOCUS ON RAKAI,

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UGANDA AS YOU'LL SEE IN GUI'S

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TALK.

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RESEARCH FOCUS TWO, REMISSION,

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WE'RE TRYING TO HARNESS BNABS IN

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COMBINATION WITH CD8 PLUS

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T-CELLS AND OTHER BIOLOGICS, AND

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RESEARCH FOCUS 3, WE HAVE TWO

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PARTS.

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FIRST WE'RE TRYING TO ENHANCE

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CTL AND NK CELL FUNCTION AND

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ALSO OVERCOME MECHANISMS BY

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WHICH SOME INFECTED CELLS RESIST

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KILLING.

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THAT'S A REALLY IMPORTANT AREA

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OF FOCUS WITHIN REACH.

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THE SECOND PART, WE'RE LOOKING

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AT MECHANISMS OF LATENCY WITH A

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FOCUS ON HOW THIS IS INFLUENCED

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BY THE PROVIRAL INTEGRATION

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SITE.

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SO JUST TO FLASH THIS BRIEFLY, I

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WANT TO MENTION THAT WE REALLY

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PRIORITIZE TRYING TO FIND

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SYNERGIES BETWEEN THESE

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DIFFERENT RFs.

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TO ME THAT'S ONE OF THE MOST

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EXCITING PARTS OF THESE DELANEY

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PROGRAMS, SO THIS IS SOMETHING

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WE THINK ABOUT VERY CAREFULLY.

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AND TO MENTION, WE ARE DOING A

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LOT OF BASIC SCIENCE BUT WE'RE

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LOOKING TOWARDS TRANSLATIONAL

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OUTCOMES, AND POTENTIALLY TAKING

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PROMISING APPROACHES AND

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PARTNERING WITH THE ACTG, AND WE

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HAVE ONE SUCH PARTNERSHIP SO

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FAR.

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THIS STUDY IS CALLED ACTG A5386.

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THERE'S TWO ARMS.

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THIS IS WITH OUR INDUSTRY

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PARTNER IMMUNITY BIOTESTING A

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SUPERAGONIST ALONE OR WITH

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BROADLY NEUTRALIZING ANTIBODIES,

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THEN THERE IS A TREATMENT

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INTERRUPTION PHASE WHERE WE HOPE

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WE SEE SOME SIGNAL OF REMISSION

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THAT WAS SEEN IN NON-HUMAN

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PRIMATES WITH THIS COMBINATION.

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AND WE'RE ABOUT A THIRD OF THE

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WAY THROUGH ACCRUAL FOR THIS

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STUDY.

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SO ONE OF THE WAYS WE LIKE TO

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MEASURE OUR PROGRESS IS HOW WELL

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WE'RE DOING AT BRINGING

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DIFFERENT INVESTIGATORS TOGETHER

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AND FORMING NEW CL COLLABORATIO.

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SO WE DO THIS WITH THESE -- EACH

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IS PROPORTIONATE TO THE NUMBER

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OF CO-PUBLICATIONS WITH

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INVESTIGATORS.

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THIS IS WHERE WE STARTED AT THE

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BEGINNING OF THE GRANT.

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IT'S REWARDING TO SEE THIS IS

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WHERE WE'RE AT 2 1/2 YEARS IN.

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THERE'S A FEW NEW INVESTIGATORS

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THAT HAVE BEEN ADDED BUT LARGELY

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THIS DENSIFICATION IS DUE TO NEW

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COLLABORATIONS, NEW PUBLICATIONS

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WITH GROUPS OF INVESTIGATORS WHO

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HADN'T WORKED TOGETHER

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PREVIOUSLY, AS WELL AS NOW

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BROADER LINES BETWEEN GROUPS WHO

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HAD COLLABORATIONS.

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IN THE LIMITED TIME I HAVE

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TODAY, I PICKED JUST TWO AREAS

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OF PROGRESS FROM THE FIRST TWO

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YEARS TO HIGHLIGHT.

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APOLOGIES TO THOSE WHO I LEFT

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OUT.

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WE'RE NOT FUNDING TRIALS IN

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REACH BUT WE'VE HAD

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OPPORTUNITIES TO CONTRIBUTE IN

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REALLY IMPORTANT WAYS TO

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EXISTING TRIALS.

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ONE OF THESE IS THE ECLEAR

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STUDY.

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ONE OF THE CHALLENGES THAT WAS

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DISCOVERED WITH THE TEAM IS THAT

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ABOUT 51% OF THESE PEOPLE HAD

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NON-SUBTYPE B HIV, SO APPLYING

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INTACT PRO FIERL DNA ASSAYS WAS

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A CHALLENGE.

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SO WE WERE ABLE TO LEVERAGE OUR

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EXPERIENCE IN ADAPTING TO

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DIVERSE ISOLATES THAT GUIN WILL

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TALK ABOUT AND DEVELOP 17 NEW

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PRIMERS, 25 CUSTOM PROBES AND

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MEASURE THE INTACT PRO VIRUS IN

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EVERYONE IN THIS STUDY.

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ONE OF THE THINGS THAT WE'VE

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DONE IN LEVERAGING THE FLEXIBLE

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ASPECTS OF THE DELANEY IS ADD

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NEW INVESTIGATORS, SO OLE IS NOW

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OFFICIALLY A REACH INVESTIGATOR

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AND NOW WE'RE GOING TO

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PRIORITIZE IN SUBSEQUENT YEARS

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TRYING TO DISCERN MECHANISMS BY

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WHICH SOME MEASURE OF CONTROL

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WAS ACHIEVED IN THIS ECLEAR

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STUDY AND OTHER TRIALS.

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THE SECOND AREA I'LL HIGHLIGHT

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IS THESE TWO STUDIES

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CHARACTERIZING THE FEATURES OF

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THE EXPANDED CLONES OF INFECTED

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CELLS IN HIV RESERVOIRS, AND

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APPROACHES FROM SOMEWHAT

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DIFFERENT AN AGAINS, THEY

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CONVERGED ON THE FINDING THAT

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SOME OF THE RESERVOIR IS

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HARBORED IN THESE CYTOTOXIC

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CD4 T-CELL CLONES AND YET SHE

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PROPOSED ONE OF THE REASONS

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THESE MAY BE HARD TO KILL IS

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THEY HAVE MECHANISMS FOR

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DEFENDING THEMSELVES AGAINST

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THEIR OWN CYTOTOXICITY.

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SO ONE OF THE OTHER

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INVESTIGATORS WE'VE ADDED GOING

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INTO YEAR THREE IS FRAU, WHO HAS

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A LARGE PANEL OF CLONES OF

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INFECTED CELLS THAT WE CAN

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REALLY PROBE FOR SOME OF THESE

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FUNCTIONAL FEATURES.

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WE HAVE A NUMBER OF POSTERS HERE

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AT THE MEETING THAT I'LL

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HIGHLIGHT HERE, AND CONGRATULATE

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THE EARLY CAREER INVESTIGATOR

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SCHOLARSHIPS THAT ARE

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HIGHLIGHTED IN YELLOW.

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I DON'T HAVE TIME TO READ

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THROUGH ALL THESE OF PLEASE DROP

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BY THE POSTERS AND SEE WHAT

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WE'VE BEEN UP TO.

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THEN OUR COMMUNITY PARTNER IS

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AVAC, WE'LL HEAR MORE ABOUT

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COMMUNITY ENGAGEMENT EFFORTS IN

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HER UPCOMING TALK.

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SO WITH THAT, I WILL WRAP UP AND

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PASS OVER TO GUIN LEE, ONE OF

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THE CO-LEADS OF RF 1 TO TELL BUS

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ADAPTING INTACT VIRAL ASSAYS I.

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>> GOOD MORNING, EVERYONE.

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MY NAME IS GUIN LEE FROM WEILL

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CORNELL MEDICINE.

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TODAY I'LL SPEAK ON BEHALF OF MY

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RF 1 COLEADS, AND OF COURSE ON

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BEHALF OF THE ENTIRE TEAM TO

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TALK ABOUT THE VIRAL RESERVOIR

222
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IN RAKAI.

223
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SO THE REACH RF 1 TEAM IS 15

224
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INVESTIGATORS STRONG.

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I'VE HIGHLIGHTED THE

226
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INVESTIGATORS HERE WHO ARE

227
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INVOLVED IN THE RAKAI PROJECT.

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OUR OVERARCHING GOAL IN RF 1 IS

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TO DEFINE A THREE-WAY

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RELATIONSHIP BETWEEN COMPOSITION

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DYNAMICS AND CD4 T-CELLS AND

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REBOUND VIRUSES.

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SO HERE TODAY I'M GOING TO TALK

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VERY SPECIFICALLY ON NON-SUBTYPE

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V HIV IN RAKAI.

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SO THE PLAIN LANGUAGE SUMMARY.

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THE KEY QUESTION HERE IS I WANT

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TO ASK, ARE NON-SUBTYPE B HIV

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DNA GENOMES, ARE THEY -- DO THEY

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HAVE THE SAME COMPOSITION

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RELATIVE TO WHAT WE KNOW ABOUT

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SUBTYPE B TODAY, BECAUSE WE HAVE

243
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A LOT OF RESERVOIR STUDIES IN

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SUBTYPE B VIRUSES, BUT IS THE

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RESERVOIR COMPOSITION THE SAME

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IN NON-SUBTYPE B VARIANTS?

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ARE WE ABLE TO ADAPT THE IPDA

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ASSAY THAT IS DEVELOPED BASED ON

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SUBTYPE B SEQUENCES ON THE

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NON-SUBTYPE B VARIANTS?

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SO WE FOUND THAT OUR KEY

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FINDINGS IS THAT THE NON-SUBTYPE

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B AND SPECIFICALLY SUBTYPE

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A1 AND D PRO VIROME GENOMES,

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THEY ACTUALLY SHARED A LOT OF

256
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COMMONALITIES WITH SUBTYPE B.

257
00:08:42,498 --> 00:08:45,335
SO FOR EXAMPLE, SUBTYPE B HAS A

258
00:08:45,335 --> 00:08:47,070
LOT OF DEFECTIVE GENOMES WHEN

259
00:08:47,070 --> 00:08:48,171
YOU LOOK AT THE PROVIRAL POOL

260
00:08:48,171 --> 00:08:50,273
AND THE SAME IS TRUE FOR SUBTYPE

261
00:08:50,273 --> 00:08:50,673
A AND D.

262
00:08:50,673 --> 00:08:53,209
FOR EXAMPLE, WE HAVE SEEN CLONAL

263
00:08:53,209 --> 00:08:55,878
EXPANSION OF SUBTYPE B VARIANTS,

264
00:08:55,878 --> 00:08:58,781
ALSO SEEING EVIDENCE OF CLONAL

265
00:08:58,781 --> 00:09:00,750
EXPRESSIONS OF TYPE A AND D.

266
00:09:00,750 --> 00:09:02,018
WEEFL ALSO HAD PRELIMINARY DATA

267
00:09:02,018 --> 00:09:05,121
TO SHOW THAT THE CD8 T-CELL

268
00:09:05,121 --> 00:09:06,522
RESPONSES IN THE RAKAI

269
00:09:06,522 --> 00:09:07,957
PARTICIPANTS BEING HIGHER THAN

270
00:09:07,957 --> 00:09:09,392
THE AMERICAN -- THEIR AMERICAN

271
00:09:09,392 --> 00:09:10,727
COUNTERPARTS.

272
00:09:10,727 --> 00:09:12,895
SO THE NEXT STEP, SO WE HAVE

273
00:09:12,895 --> 00:09:15,732
CURRENTLY INSTALLED OR IN THE

274
00:09:15,732 --> 00:09:18,468
MID EVIDENTLY INSTALLING A DDPCR

275
00:09:18,468 --> 00:09:22,739
PLATFORM IN RAKAI TO HELP

276
00:09:22,739 --> 00:09:24,240
INSTALL THE DDPCR MACHINE ON

277
00:09:24,240 --> 00:09:24,807
SITE.

278
00:09:24,807 --> 00:09:26,876
SO THEN THE UGANDA SCIENTISTS

279
00:09:26,876 --> 00:09:27,977
CAN ACTUALLY RUN THIS ASSAY

280
00:09:27,977 --> 00:09:31,614
THERE.

281
00:09:31,614 --> 00:09:33,316
SO MOVING FORWARD, WE WANT TO

282
00:09:33,316 --> 00:09:35,118
APPLY THE DDPCR ASSAY TO ALL

283
00:09:35,118 --> 00:09:37,086
STUDY PARTICIPANTS LONGITUDALLY

284
00:09:37,086 --> 00:09:38,821
IN THE RAKAI COHORT, AND WE WANT

285
00:09:38,821 --> 00:09:40,790
TO SEE WHETHER THERE'S

286
00:09:40,790 --> 00:09:43,659
SIGNIFICANT CD8 T-CELL RESPONSES

287
00:09:43,659 --> 00:09:45,161
CORRELATION WITH THE RESERVOIR

288
00:09:45,161 --> 00:09:48,030
MEASUREMENTS.

289
00:09:48,030 --> 00:09:49,866
SO TO INTRODUCE THE COHORT, THE

290
00:09:49,866 --> 00:09:52,301
RAKAI LATENT RESERVOIR

291
00:09:52,301 --> 00:09:56,105
LONGITUDAL COHORT HAS 19 STUDY

292
00:09:56,105 --> 00:09:56,539
PARTICIPANTS.

293
00:09:56,539 --> 00:09:58,975
IT'S HOUSED WITHIN A 30,000

294
00:09:58,975 --> 00:10:00,176
REGIONAL HIV TREATMENT PROGRAM

295
00:10:00,176 --> 00:10:01,677
COHORT WHERE THE CLINICAL AND

296
00:10:01,677 --> 00:10:04,380
TREATMENT HISTORIES ARE

297
00:10:04,380 --> 00:10:07,450
AVAILABLE, SO PARTICIPANTS WERE

298
00:10:07,450 --> 00:10:13,022
ENROLLED MEDIAN SEVEN YEARS POST

299
00:10:13,022 --> 00:10:17,093
TREATMENT.

300
00:10:17,093 --> 00:10:19,128
PBMC AND PLASMA ARE COLLECTED

301
00:10:19,128 --> 00:10:24,033
AND WE PERFORMED QVOA AND FRIP

302
00:10:24,033 --> 00:10:25,902
SEQUENCING AND DDPCR ON THESE

303
00:10:25,902 --> 00:10:28,204
STUDY PARTICIPANTS.

304
00:10:28,204 --> 00:10:29,939
SO THE RAKAI RESERVOIR STUDY

305
00:10:29,939 --> 00:10:32,341
REALLY STARTED WITH THIS

306
00:10:32,341 --> 00:10:33,876
OBSERVATION THAT OUR OWN

307
00:10:33,876 --> 00:10:34,877
DR. JESSICA SALZWEDEL MADE THAT

308
00:10:34,877 --> 00:10:37,647
THE RAKAI RESERVOIR IS ACTUALLY

309
00:10:37,647 --> 00:10:39,549
THREE FOLD LOWER IN TERMS OF IPD

310
00:10:39,549 --> 00:10:40,783
VALUES COMPARED TO THE NORTH

311
00:10:40,783 --> 00:10:42,518
AMERICAN COUNTERPARTS AND SO IT

312
00:10:42,518 --> 00:10:45,488
SHOWS THAT THE NON-SUBTYPE B --

313
00:10:45,488 --> 00:10:46,556
AT LEAST IN THIS POPULATION, IT

314
00:10:46,556 --> 00:10:48,424
MIGHT NOT BE THE SAME AS WHAT

315
00:10:48,424 --> 00:10:50,526
WE'VE USUALLY SEEN IN THE

316
00:10:50,526 --> 00:10:54,797
SUBTYPE B COHORTS.

317
00:10:54,797 --> 00:10:56,232
SO FURTHERMORE WE HAVE THE

318
00:10:56,232 --> 00:10:58,801
LATEST PRELIMINARY DATA FROM THE

319
00:10:58,801 --> 00:11:02,104
RF 1 THAT IF YOU LOOK AT PANEL

320
00:11:02,104 --> 00:11:05,141
1, WE ARE COMPARING THE RAKAI

321
00:11:05,141 --> 00:11:09,178
CTCD8 T-CELL RESPONSES TO A NORH

322
00:11:09,178 --> 00:11:09,579
AMERICAN COHORT.

323
00:11:09,579 --> 00:11:11,614
YOU CAN SEE THAT THE RAKAI STUDY

324
00:11:11,614 --> 00:11:14,016
PARTICIPANTS HAVE HIGHER

325
00:11:14,016 --> 00:11:16,352
INTERFERON GAMMA-SPECIFIC T-CELL

326
00:11:16,352 --> 00:11:18,054
RESPONSES IN TERMS OF MAGNITUDE

327
00:11:18,054 --> 00:11:20,590
RELATIVE TO THE NORTH AMERICAN

328
00:11:20,590 --> 00:11:24,393
COUNTERPARTS.

329
00:11:24,393 --> 00:11:27,363
SO THE -- IS ALSO HIGHER

330
00:11:27,363 --> 00:11:28,231
SPECIFICALLY IN ENVELOPE AND

331
00:11:28,231 --> 00:11:31,434
ALSO IN CMV IN THIS RAKAI

332
00:11:31,434 --> 00:11:31,734
COHORT.

333
00:11:31,734 --> 00:11:33,169
SO SOMETHING IS DIFFERENT AT

334
00:11:33,169 --> 00:11:36,005
LEAST IN THE CD8 T-CELL

335
00:11:36,005 --> 00:11:36,973
RESPONSES.

336
00:11:36,973 --> 00:11:40,576
IN THE SECOND PANEL, CAN YOU SEE

337
00:11:40,576 --> 00:11:47,149
THAT THE MAGNITUDE OF -- HAS AN

338
00:11:47,149 --> 00:11:48,684
INVERSE CORELATION WITH THE IPD

339
00:11:48,684 --> 00:11:49,986
MEASUREMENTS IN THIS RAKAI

340
00:11:49,986 --> 00:11:50,553
COHORT.

341
00:11:50,553 --> 00:11:52,855
WHAT THAT MEANS IS THE HIGHER

342
00:11:52,855 --> 00:11:55,091
THE -- WE SEE A CORRELATION THAT

343
00:11:55,091 --> 00:11:57,360
THERE'S A HIGHER -- RESPONSES

344
00:11:57,360 --> 00:12:02,365
AND THERE'S A LOWER IUPM VALUES.

345
00:12:02,365 --> 00:12:04,233
IT MEANS THAT WHEN THE T-CELL

346
00:12:04,233 --> 00:12:05,568
MAGNITUDE RESPONSES IS STRONGER

347
00:12:05,568 --> 00:12:09,572
IN THE CD8 NEF-SPECIFIC

348
00:12:09,572 --> 00:12:11,541
RESPONSES, IT'S CORELATED WITH A

349
00:12:11,541 --> 00:12:14,944
LOWER IUPM VALUES SO MAYBE THAT

350
00:12:14,944 --> 00:12:17,079
SUGGESTED THAT THE CD8 T-CELLS

351
00:12:17,079 --> 00:12:18,314
ARE MAKING A DENT ON THE

352
00:12:18,314 --> 00:12:20,082
RESERVOIR, IS SHAPING THE

353
00:12:20,082 --> 00:12:20,616
RESERVOIR PROFILE.

354
00:12:20,616 --> 00:12:22,385
SO WE WANT TO STUDY THE SHAPES

355
00:12:22,385 --> 00:12:24,253
OF THE RESERVOIR, WHAT IS INSIDE

356
00:12:24,253 --> 00:12:24,987
THE RESERVOIR.

357
00:12:24,987 --> 00:12:29,258
SO HERE WE HAVE MATCHING VIRAL

358
00:12:29,258 --> 00:12:30,893
GENOME SEQUENCES OBTAINED FROM

359
00:12:30,893 --> 00:12:31,994
20 TOLEDO NORS.

360
00:12:31,994 --> 00:12:36,032
THERE ARE SUBTYPE A1 -- WE HAVE

361
00:12:36,032 --> 00:12:37,900
FOUR INDIVIDUALS, NINE SUBTYPE D

362
00:12:37,900 --> 00:12:39,201
INDIVIDUALS AND NINE INDIVIDUALS

363
00:12:39,201 --> 00:12:40,836
WITH RECOMBINANT AD VIRUSES.

364
00:12:40,836 --> 00:12:43,573
IF YOU LOOK AT THE RECOMBINANTS,

365
00:12:43,573 --> 00:12:45,875
SO EACH VERTICAL ROW -- SORRY,

366
00:12:45,875 --> 00:12:46,976
EACH HORIZONTAL ROW HERE

367
00:12:46,976 --> 00:12:47,944
REPRESENTS A SINGLE INDIVIDUAL.

368
00:12:47,944 --> 00:12:51,681
IF YOU LOOK AT THE BOTTOM STACK

369
00:12:51,681 --> 00:12:55,718
THERE, THE RECOMBINANTS, THE

370
00:12:55,718 --> 00:12:58,020
RECOMBINANT IN THIS COHORT IS

371
00:12:58,020 --> 00:13:00,089
ACTUALLY VERY COMPLEX.

372
00:13:00,089 --> 00:13:01,524
RED STANDS FOR SUBTYPE D AND

373
00:13:01,524 --> 00:13:03,159
BLUE STANDS FOR SUBTYPE A, AND

374
00:13:03,159 --> 00:13:06,329
YOU CAN SEE THAT THERE ARE A LOT

375
00:13:06,329 --> 00:13:07,763
OF THESE INTERSUBTYPE REIMI

376
00:13:07,763 --> 00:13:09,065
NANTZ THAT ARE CIRCULATING IN

377
00:13:09,065 --> 00:13:09,498
THIS COHORT.

378
00:13:09,498 --> 00:13:11,467
SOME OF THEM START WITH A

379
00:13:11,467 --> 00:13:12,568
SUBTYPE A GAP AND THEN IT

380
00:13:12,568 --> 00:13:15,071
BECOMES A SUBTYPE D PROTEASE AND

381
00:13:15,071 --> 00:13:19,008
RT AND THEN IT BECOMES A SUBTYPE

382
00:13:19,008 --> 00:13:20,343
A -- AGAIN, AND THEN IT TURNS

383
00:13:20,343 --> 00:13:21,377
BACK INTO SUBTYPE D.

384
00:13:21,377 --> 00:13:24,113
SO THE RECOMBINATION SITUATION

385
00:13:24,113 --> 00:13:26,349
IN A COHORT LIKE THIS IS REALLY

386
00:13:26,349 --> 00:13:29,852
COMPLEX, AND ALL OF THE

387
00:13:29,852 --> 00:13:31,053
RECOMBINANT DONORS DON'T HAVE

388
00:13:31,053 --> 00:13:32,688
THE SAME RECOMBINATION BREAK

389
00:13:32,688 --> 00:13:33,022
POINTS.

390
00:13:33,022 --> 00:13:34,190
FOR EXAMPLE IF A PERSON WALKS

391
00:13:34,190 --> 00:13:35,424
INTO A CLINIC, YOU WOULD NOT BE

392
00:13:35,424 --> 00:13:36,859
ABLE TO IMMEDIATELY KNOW WHETHER

393
00:13:36,859 --> 00:13:38,928
THIS PERSON IS IMPACTED BY

394
00:13:38,928 --> 00:13:41,230
SUBTYPE A OR SUBTYPE D VIRUSES,

395
00:13:41,230 --> 00:13:45,167
AND PERHAPS THE ENVELOPE REGION

396
00:13:45,167 --> 00:13:47,903
VERSUS THE G AK REGION WHICH ARE

397
00:13:47,903 --> 00:13:48,671
THOSE TARGET SITES WOULD NOT

398
00:13:48,671 --> 00:13:50,840
HAVE THE SAME SUBTYPE, AND SO WE

399
00:13:50,840 --> 00:13:52,541
WANT TO DEVELOP A METHOD THAT

400
00:13:52,541 --> 00:13:54,143
WOULD COVER BOTH SUBTYPES IN

401
00:13:54,143 --> 00:13:56,312
THIS COHORT AND SO WE WILL BE

402
00:13:56,312 --> 00:14:01,183
DOING A COHORT-SPECIFIC IPD

403
00:14:01,183 --> 00:14:01,684
DEVELOPMENT APPROACH.

404
00:14:01,684 --> 00:14:03,319
SO GOING BACK TO THE RESERVOIR,

405
00:14:03,319 --> 00:14:05,421
SO IN THE STUDY WE'VE OBSERVED

406
00:14:05,421 --> 00:14:07,023
THAT THE SUBTYPE A AND D

407
00:14:07,023 --> 00:14:08,658
RESERVOIRS ARE VERY SIMILAR TO

408
00:14:08,658 --> 00:14:10,760
SUBTYPE B IN THE SENSE THAT

409
00:14:10,760 --> 00:14:13,029
THERE ARE VERY FEW INTACT

410
00:14:13,029 --> 00:14:15,898
VIRUSES, AND THERE ARE A LOT OF

411
00:14:15,898 --> 00:14:17,867
DEFECTIVE VIRAL GENOME

412
00:14:17,867 --> 00:14:19,835
CATEGORIES VERY SIMILAR IN TERMS

413
00:14:19,835 --> 00:14:21,470
OF HAVING THE LARGE TRUNCATIONS,

414
00:14:21,470 --> 00:14:23,539
HAVING HYPERMUTATIONS, AND WE'VE

415
00:14:23,539 --> 00:14:25,074
ALSO SEEN EVIDENCE OF CLONAL

416
00:14:25,074 --> 00:14:28,444
EXPANSION.

417
00:14:28,444 --> 00:14:30,746
SO HERE'S AN EXAMPLE OF A

418
00:14:30,746 --> 00:14:31,414
REPRESENTATIVE INDIVIDUAL THAT

419
00:14:31,414 --> 00:14:34,383
IS IMPACTED BY SUBTYPE A HIV.

420
00:14:34,383 --> 00:14:36,452
SO YOU CAN SEE THAT THE DARK

421
00:14:36,452 --> 00:14:38,621
BLUE STACKS OF BARS AT THE TOP

422
00:14:38,621 --> 00:14:40,189
ARE THE INTACT VIRUSES.

423
00:14:40,189 --> 00:14:42,058
AND ALL OF THE OTHER VIRAL

424
00:14:42,058 --> 00:14:43,359
GENOMES AT THE BOTTOM WITH

425
00:14:43,359 --> 00:14:45,695
LIGHTER COLORS ARE

426
00:14:45,695 --> 00:14:46,429
GENOME-DEFECTIVE VIRUSES.

427
00:14:46,429 --> 00:14:48,397
SO I'VE HIGHLIGHTED WITH

428
00:14:48,397 --> 00:14:52,001
VERTICAL LINES OF THE IPDA SITE

429
00:14:52,001 --> 00:14:53,569
AND ENVELOPE BINDING SITES.

430
00:14:53,569 --> 00:14:55,304
HERE'S A SUBTYPE D DONOR.

431
00:14:55,304 --> 00:14:56,872
AND YOU CAN ALREADY SEE THE

432
00:14:56,872 --> 00:14:57,406
SIMILARITIES.

433
00:14:57,406 --> 00:14:59,008
IT'S VERY SIMILAR TO WHAT WE SEE

434
00:14:59,008 --> 00:15:01,210
USUALLY IN SUBTYPE B.

435
00:15:01,210 --> 00:15:03,279
NOW, WHAT ABOUT THE IPDA BINDING

436
00:15:03,279 --> 00:15:04,280
SITES?

437
00:15:04,280 --> 00:15:05,915
SO IF YOU COUNT UP THE NUMBER OF

438
00:15:05,915 --> 00:15:08,184
GENOMES THAT CONTAINS BOTH IPDA

439
00:15:08,184 --> 00:15:11,487
BINDING SITES, WHICH IS A

440
00:15:11,487 --> 00:15:12,788
PREDICTIVE MARKER FOR A GENOME

441
00:15:12,788 --> 00:15:13,989
BEING INTACT, SO IF YOU HAVE

442
00:15:13,989 --> 00:15:16,492
BOTH IPDA BINDING SITES, THE

443
00:15:16,492 --> 00:15:17,927
GENE IS MORE LIKELY TO BE

444
00:15:17,927 --> 00:15:18,260
INTACT.

445
00:15:18,260 --> 00:15:20,129
SO OBVIOUSLY ALL OF THE INTACT

446
00:15:20,129 --> 00:15:21,964
VIRUSES WOULD CONTAIN BOTH IPDA

447
00:15:21,964 --> 00:15:25,267
BINDING SITES, BUT IF YOU COUNT

448
00:15:25,267 --> 00:15:28,537
THE GENOME-DEFECTIVE VIRUSES, WE

449
00:15:28,537 --> 00:15:32,308
SAW 95% WOULD EITHER HAVE ONE

450
00:15:32,308 --> 00:15:34,977
MISSING OR MISSING BOTH IPDA

451
00:15:34,977 --> 00:15:35,978
AND -- BINDING SITES.

452
00:15:35,978 --> 00:15:39,148
THAT MEANS THAT WE HAVE 100%

453
00:15:39,148 --> 00:15:40,249
SENSITIVITY AND 95% SPECIFICITY

454
00:15:40,249 --> 00:15:42,685
IN TERMS OF IF WE JUST LOOK AT

455
00:15:42,685 --> 00:15:45,821
THE LOCATIONS OF THESE PRIMER

456
00:15:45,821 --> 00:15:47,790
AND PRO BINDING SITES, IF WE USE

457
00:15:47,790 --> 00:15:50,092
THE ORIGINAL IPDA DESIGN ON THIS

458
00:15:50,092 --> 00:15:50,426
COHORT.

459
00:15:50,426 --> 00:15:53,896
BUT OF COURSE THE

460
00:15:53,896 --> 00:15:54,563
SENSITIVITY/SPECIFICITY ISSUE IS

461
00:15:54,563 --> 00:15:56,966
NOT JUST LIMITED TO WHERE THE

462
00:15:56,966 --> 00:15:59,502
PRIMERS AND PROBES LOCATED.

463
00:15:59,502 --> 00:16:00,903
SEQUENCE AND DIVERSITY ALSO

464
00:16:00,903 --> 00:16:01,137
MATTERS.

465
00:16:01,137 --> 00:16:04,073
SO LET'S LOOK AT A SEQUENCE

466
00:16:04,073 --> 00:16:04,540
DIVERSITY.

467
00:16:04,540 --> 00:16:09,645
ALL OF THE POLYMORPHISMS WE

468
00:16:09,645 --> 00:16:15,551
IDENTIFIED -- THIS IS THE FIRST

469
00:16:15,551 --> 00:16:17,753
REGION, AND THE BOTTOM FOUR ROWS

470
00:16:17,753 --> 00:16:20,256
ARE THE RAKAI COHORT

471
00:16:20,256 --> 00:16:20,689
OBSERVATIONS.

472
00:16:20,689 --> 00:16:23,759
AND YOU CAN SEE THAT THE PSI

473
00:16:23,759 --> 00:16:25,628
FORWARD AND REVERSE PRIMERS

474
00:16:25,628 --> 00:16:27,496
PRETTY MUCH MATCH UP THE IPDA

475
00:16:27,496 --> 00:16:31,433
WITH A FEW POLYMORPHISMS BUT THE

476
00:16:31,433 --> 00:16:33,302
PSI PROBE HAS A LOT MORE

477
00:16:33,302 --> 00:16:34,603
OBSERVED IN THE RAKAI COHORT.

478
00:16:34,603 --> 00:16:37,439
THE SAME IS TRUE IN THE ENVELOPE

479
00:16:37,439 --> 00:16:37,840
REGION.

480
00:16:37,840 --> 00:16:39,742
THERE ARE -- WE SEE DIVERSITY.

481
00:16:39,742 --> 00:16:42,578
AND SO HOW DO WE ACCOUNT FOR

482
00:16:42,578 --> 00:16:44,213
THIS DIVERSITY?

483
00:16:44,213 --> 00:16:45,548
FIRST LET'S SEE WHETHER THE

484
00:16:45,548 --> 00:16:48,384
ORIGINAL IPDA DESIGN AND THE

485
00:16:48,384 --> 00:16:49,685
ORIGINAL PRIMERS AND PROBE

486
00:16:49,685 --> 00:16:52,822
SEQUENCES WOULD ACTUALLY BIND TO

487
00:16:52,822 --> 00:16:54,623
THE SAMPLES IN THIS RAKAI

488
00:16:54,623 --> 00:16:55,491
COHORT.

489
00:16:55,491 --> 00:16:59,762
SO ON PANEL A HERE, WE SUBJECT A

490
00:16:59,762 --> 00:17:01,063
SUBTYPE D SAMPLE THROUGH THE

491
00:17:01,063 --> 00:17:03,132
ORIGINAL IPDA AND UNFORTUNATELY

492
00:17:03,132 --> 00:17:05,835
IPDA ACTUALLY FAILED IN THE PSI

493
00:17:05,835 --> 00:17:07,670
REGION AND IT ONLY PRODUCED

494
00:17:07,670 --> 00:17:09,171
ENVELOPE SIGNALS.

495
00:17:09,171 --> 00:17:11,774
BOTTOM THERE, WE USED AN

496
00:17:11,774 --> 00:17:14,410
ADAPTIVE DESIGN, DESIGNED

497
00:17:14,410 --> 00:17:17,112
SPECIFICALLY TO TAKE INTO

498
00:17:17,112 --> 00:17:19,882
ACCOUNT FOR THE GENETIC

499
00:17:19,882 --> 00:17:22,518
DIVERSITY AND WE WERE ABLE TO

500
00:17:22,518 --> 00:17:24,687
RESCUE THE SIGNALS.

501
00:17:24,687 --> 00:17:27,189
SO OUR APPROACH IS TO USE

502
00:17:27,189 --> 00:17:28,490
DEGENERATIVE BASIS.

503
00:17:28,490 --> 00:17:30,426
FOR EACH OF THE POLYMORPHIC

504
00:17:30,426 --> 00:17:31,927
SITES THAT WE'VE DEVELOPED --

505
00:17:31,927 --> 00:17:34,530
THAT WE'VE OBSERVED IN THIS IPDA

506
00:17:34,530 --> 00:17:35,965
PRIMERS AND PROBES BINDING SITE,

507
00:17:35,965 --> 00:17:37,700
WE INCORPORATED DEGENERATIVE

508
00:17:37,700 --> 00:17:38,367
BASE IN THE REGION.

509
00:17:38,367 --> 00:17:41,437
SO WHAT I MEAN BY

510
00:17:41,437 --> 00:17:43,072
DEGENERATIVE-BASED APPROACH IS

511
00:17:43,072 --> 00:17:44,473
THAT FOR EXAMPLE, IN A VERY

512
00:17:44,473 --> 00:17:48,077
SPECIFIC SITE, IF WE SEE 50% --

513
00:17:48,077 --> 00:17:50,279
OR WE SEE POLYMORPHISMS THAT

514
00:17:50,279 --> 00:17:53,115
CONSIST OF 50% A AND 50% G, WE

515
00:17:53,115 --> 00:17:54,550
DESIGN A PRIMER MIX THAT

516
00:17:54,550 --> 00:18:00,022
CONTAINS WI 50% A NUCLEOTIDES AD

517
00:18:00,022 --> 00:18:02,524
50% G, ALL MIXED UP AND PUT INTO

518
00:18:02,524 --> 00:18:02,958
THE REACTION.

519
00:18:02,958 --> 00:18:05,160
SO FOR COMPASS IN THE SPI PROBE

520
00:18:05,160 --> 00:18:06,528
THERE WILL BE 60 VARIATIONS SO

521
00:18:06,528 --> 00:18:07,663
IF YOU COUNT UP TO THE MATH,

522
00:18:07,663 --> 00:18:09,765
THERE WILL BE 64 DIFFERENT

523
00:18:09,765 --> 00:18:10,666
SPECIES OF THE PROBE SEQUENCE

524
00:18:10,666 --> 00:18:12,968
THAT WILL BE IN THE MIX.

525
00:18:12,968 --> 00:18:15,437
AND THIS ACTUALLY HAS SHOWN TO

526
00:18:15,437 --> 00:18:17,840
BE ENOUGH TO PRODUCE A STRONG

527
00:18:17,840 --> 00:18:21,343
SIGNAL TO DETECT THE SUBTYPE D

528
00:18:21,343 --> 00:18:22,645
SAMPLES THAT RESCUE TO FAILURE.

529
00:18:22,645 --> 00:18:23,946
SO WE ARE APPLYING THIS

530
00:18:23,946 --> 00:18:26,282
TECHNOLOGY TO OTHER SAMPLES,

531
00:18:26,282 --> 00:18:28,117
INCLUDING SUBTYPE A1 AND D AND

532
00:18:28,117 --> 00:18:30,219
SUBTYPE A SAMPLES.

533
00:18:30,219 --> 00:18:32,288
SO WE ARE ALSO VERY PROUD TO

534
00:18:32,288 --> 00:18:34,456
ANNOUNCE THAT WE ARE

535
00:18:34,456 --> 00:18:36,091
TRANSFERRING THE TECHNOLOGY TO

536
00:18:36,091 --> 00:18:39,595
THE UGANDAN SCIENTISTS AND

537
00:18:39,595 --> 00:18:42,231
INSTALLING A DDPCR MACHINE ON

538
00:18:42,231 --> 00:18:43,532
SITE AND OUR TEAM IS CURRENTLY

539
00:18:43,532 --> 00:18:45,067
ON SITE TO HELP WITH THE DDPCR

540
00:18:45,067 --> 00:18:45,834
SETUP.

541
00:18:45,834 --> 00:18:48,671
AND THIS IS ALSO THE FIRST DDPCR

542
00:18:48,671 --> 00:18:50,005
MACHINE THAT IS INTRODUCED INTO

543
00:18:50,005 --> 00:18:52,274
THE SUB-SAHARAN AFRICAN REGION

544
00:18:52,274 --> 00:18:53,609
OUTSIDE OF SOUTH AFRICA.

545
00:18:53,609 --> 00:18:59,415
SO WE'RE VERY PROUD OF THAT.

546
00:18:59,415 --> 00:19:00,816
SO IN THE NEXT STEP, NOW THAT WE

547
00:19:00,816 --> 00:19:02,885
HAVE AN ADAPTED IPDA ASSAY, WE

548
00:19:02,885 --> 00:19:05,521
WANT TO USE THIS TO ENSURE

549
00:19:05,521 --> 00:19:06,522
LONGITUDALLY THE RELATIVE

550
00:19:06,522 --> 00:19:09,358
CHANGES OF GENOME INTACT

551
00:19:09,358 --> 00:19:10,893
VIRUSES, DEFECTIVE VIRUSES, WE

552
00:19:10,893 --> 00:19:13,429
ALSO HAVE THE IUPM VALUES FOR

553
00:19:13,429 --> 00:19:16,465
THESE PARTICIPANTS AND WE ALSO

554
00:19:16,465 --> 00:19:19,301
WANT TO CORRELATE THE T-CELL

555
00:19:19,301 --> 00:19:20,536
RESPONSES IN THIS COHORT WITH

556
00:19:20,536 --> 00:19:23,072
THE RESERVOIR DYNAMICS.

557
00:19:23,072 --> 00:19:24,340
THIS IS A HUGE TEAM EFFORT.

558
00:19:24,340 --> 00:19:25,874
IT'S NOT POSSIBLE WITHOUT ALL OF

559
00:19:25,874 --> 00:19:28,444
THE TEAM MEMBERS HERE INVOLVED

560
00:19:28,444 --> 00:19:30,112
IN THE STUDY, SO I THANK

561
00:19:30,112 --> 00:19:31,347
EVERYONE AND OF COURSE ALL THE

562
00:19:31,347 --> 00:19:33,082
RAKAI STUDY PARTICIPANTS WHO ARE

563
00:19:33,082 --> 00:19:33,349
INVOLVED.

564
00:19:33,349 --> 00:19:33,983
THANK YOU.

565
00:19:33,983 --> 00:19:44,159
[APPLAUSE]

566
00:20:46,088 --> 00:20:49,158
>> SO NOW I'M GOING TO
TALK

567
00:20:49,158 --> 00:20:50,426
ABOUT RF 2.

568
00:20:50,426 --> 00:20:52,661
SO AS BRAD INTRODUCED, OUR

569
00:20:52,661 --> 00:20:55,831
COLLABORATORY IS REALLY FOCUSED

570
00:20:55,831 --> 00:20:57,266
ON IMMUNOLOGIC APPROACHES.

571
00:20:57,266 --> 00:21:00,736
IN PART OF RF 2, WE ARE TRYING

572
00:21:00,736 --> 00:21:03,272
TO LEVERAGE CLINICAL TRIAL

573
00:21:03,272 --> 00:21:06,008
SAMPLES, ALL STUDIES WE HAVE

574
00:21:06,008 --> 00:21:07,709
CONDUCTED OR ARE ONGOING THAT

575
00:21:07,709 --> 00:21:10,612
ARE TESTING A COMBINATION OF B

576
00:21:10,612 --> 00:21:12,915
NABS WITH OTHER STRATEGIES.

577
00:21:12,915 --> 00:21:15,084
AND THEN HERE, THE POINT IS TO

578
00:21:15,084 --> 00:21:17,286
TRY TO DETERMINE THEIR VIROLOGIC

579
00:21:17,286 --> 00:21:18,587
AND IMMUNOLOGIC EFFECTS WITHIN

580
00:21:18,587 --> 00:21:22,324
THE CONTEXT OF ACHIEVING

581
00:21:22,324 --> 00:21:22,858
NEUROLOGIC CONTROL.

582
00:21:22,858 --> 00:21:24,593
SO HERE ARE THE RF

583
00:21:24,593 --> 00:21:25,594
2 INVESTIGATORS, AND THEN THE

584
00:21:25,594 --> 00:21:26,361
STUDIES I'M GOING TO BE

585
00:21:26,361 --> 00:21:27,229
DISCUSSING TODAY ARE STUDIES

586
00:21:27,229 --> 00:21:28,964
THAT WE CONDUCTED AT ROCKEFELLER

587
00:21:28,964 --> 00:21:31,266
AND STUDIES THAT WE ARE

588
00:21:31,266 --> 00:21:36,572
CONDUCTING IN COLLABORATION WITH

589
00:21:36,572 --> 00:21:37,773
OTHERS.

590
00:21:37,773 --> 00:21:39,508
SO THE AIM OF THE RF 2 THAT I'LL

591
00:21:39,508 --> 00:21:42,344
BE DISCUSSING STATES THE

592
00:21:42,344 --> 00:21:42,678
FOLLOWING.

593
00:21:42,678 --> 00:21:44,546
SO THE GOAL IS TO DEFINE

594
00:21:44,546 --> 00:21:47,916
MECHANISMS OF CD8 OR NK CELL

595
00:21:47,916 --> 00:21:50,786
MEDIATED CONTROL OF VIREMIA

596
00:21:50,786 --> 00:21:52,654
FOLLOWING DIFFERENT IMMUNOLOGIC

597
00:21:52,654 --> 00:21:52,955
STRATEGIES.

598
00:21:52,955 --> 00:21:53,956
WE'RE TRYING TO LEVERAGE WHAT WE

599
00:21:53,956 --> 00:21:55,224
CAN LEARN FROM DIFFERENT

600
00:21:55,224 --> 00:21:57,192
CLINICAL TRIALS.

601
00:21:57,192 --> 00:21:59,194
SO THIS FIGURE HERE, I'M TRYING

602
00:21:59,194 --> 00:22:00,929
TO ILLUSTRATE STUDYS THAT WE ARE

603
00:22:00,929 --> 00:22:03,999
CONDUCTING OR HAVE ACCESS TO,

604
00:22:03,999 --> 00:22:05,968
WIDER STUDIES ARE STILL IN

605
00:22:05,968 --> 00:22:08,604
DEVELOPMDEVELOPMENT, IN RED ARES

606
00:22:08,604 --> 00:22:09,705
ONGOING AND IN BLUE ARE

607
00:22:09,705 --> 00:22:10,472
COMPLETED STUDIES.

608
00:22:10,472 --> 00:22:12,307
SO ACROSS THE SERIES OF STUDIES,

609
00:22:12,307 --> 00:22:13,976
WE ARE TESTING BNABS IN

610
00:22:13,976 --> 00:22:14,510
DIFFERENT CONTEXTS.

611
00:22:14,510 --> 00:22:19,148
SO EITHER DOING ACUTE INFECTION,

612
00:22:19,148 --> 00:22:21,116
CHRONIC INFECTION AT ART

613
00:22:21,116 --> 00:22:25,287
INITIATION, ARTE ART RESTART, AE

614
00:22:25,287 --> 00:22:28,557
OR IN COMBINATION WITH AGONISTS

615
00:22:28,557 --> 00:22:30,526
OR IL15 SUPERAGONIST.

616
00:22:30,526 --> 00:22:32,361
SO THIS IS A SUMMARY OF STUDIES

617
00:22:32,361 --> 00:22:34,663
THAT WE'VE DONE AT ROCKEFELLER.

618
00:22:34,663 --> 00:22:37,499
SO WHILE OUR STUDIES ARE SMALL,

619
00:22:37,499 --> 00:22:39,134
WE'VE SHOWN THAT A COMBINATION

620
00:22:39,134 --> 00:22:42,404
OF TWO ANTIBODIES ARE ABLE TO

621
00:22:42,404 --> 00:22:43,639
MAINTAIN SUPPRESSION IN

622
00:22:43,639 --> 00:22:44,806
INDIVIDUALS THAT HARBOR

623
00:22:44,806 --> 00:22:45,541
SENSITIVE VIRUSES.

624
00:22:45,541 --> 00:22:46,642
IN ADDITION TO THAT, WE STARTED

625
00:22:46,642 --> 00:22:51,813
TO PROBE TO SEE IF THEY HAD

626
00:22:51,813 --> 00:22:52,381
OTHER EFFECTS.

627
00:22:52,381 --> 00:22:53,715
THE FIRST GRAPHIC COMES FROM THE

628
00:22:53,715 --> 00:22:57,186
FIRST STUDY WE DID WHERE WE SHOW

629
00:22:57,186 --> 00:23:00,556
AN INFUSION IN VIREMIC

630
00:23:00,556 --> 00:23:02,357
INDIVIDUALS OR ART-SUPPRESSED

631
00:23:02,357 --> 00:23:03,625
INDIVIDUALS LED TO INCREASE IN

632
00:23:03,625 --> 00:23:05,260
THEIR AUTOLOGOUS

633
00:23:05,260 --> 00:23:05,794
NEUTRALIZATION -- OVER THE

634
00:23:05,794 --> 00:23:07,930
COURSE OF SIX MONTHS.

635
00:23:07,930 --> 00:23:08,897
LOOKING AT THEIR T-CELL

636
00:23:08,897 --> 00:23:10,065
RESPONSES IN A STUDY WHERE WE

637
00:23:10,065 --> 00:23:12,067
DID THE TWO ANTIBODIES OVER THE

638
00:23:12,067 --> 00:23:14,937
COURSE OF SIX WEEKS DURING ART

639
00:23:14,937 --> 00:23:16,004
INTERRUPTION, WE ALSO SAW THERE

640
00:23:16,004 --> 00:23:18,740
WAS AN INCREASE IN GAG-SPECIFIC

641
00:23:18,740 --> 00:23:20,375
CD8 AND CD4 T-CELL RESPONSES

642
00:23:20,375 --> 00:23:22,811
DURING THIS BNAB MEDIATED VIRUS

643
00:23:22,811 --> 00:23:23,779
SUPPRESSION.

644
00:23:23,779 --> 00:23:24,980
BUT THOSE CHANGES WERE

645
00:23:24,980 --> 00:23:25,981
TRANSIENT.

646
00:23:25,981 --> 00:23:31,220
MORE RECENTLY, A STUDY WE DID

647
00:23:31,220 --> 00:23:35,490
WITH CHRISTIAN GAEBLER, HE USED

648
00:23:35,490 --> 00:23:35,924
Q4PCR.

649
00:23:35,924 --> 00:23:37,459
IN THIS STUDY THE PARTICIPANTS

650
00:23:37,459 --> 00:23:38,327
RECEIVED ANTIBODIES OVER THE

651
00:23:38,327 --> 00:23:39,761
COURSE OF FIVE MONTHS AND THEN

652
00:23:39,761 --> 00:23:40,862
HE FOUND THAT THERE WAS THIS

653
00:23:40,862 --> 00:23:42,698
SMALL BUT STATISTICALLY

654
00:23:42,698 --> 00:23:43,599
SIGNIFICANT CHANGE IN THE NUMBER

655
00:23:43,599 --> 00:23:45,334
OF INTACT PRO VIRUSES DURING

656
00:23:45,334 --> 00:23:48,070
THIS COURSE OF SIX MONTHS IN

657
00:23:48,070 --> 00:23:49,905
CONTRAST TO THE -- VIRUS.

658
00:23:49,905 --> 00:23:51,340
SO PUTTING ALL OF THIS TOGETHER,

659
00:23:51,340 --> 00:23:54,076
WE THINK THESE ARE SMALL SIGNALS

660
00:23:54,076 --> 00:23:56,478
THAT THE ANTIBODIES MAY IN FACT

661
00:23:56,478 --> 00:23:58,880
BE INTERFERING WITH HIV

662
00:23:58,880 --> 00:23:59,548
PERSISTENCE IN VIVO.

663
00:23:59,548 --> 00:24:00,649
HOWEVER NONE OF THESE CHANGES

664
00:24:00,649 --> 00:24:02,084
HAVE BEEN SUFFICIENT TO PREVENT

665
00:24:02,084 --> 00:24:06,421
RETURN OF VIREMIA CONSISTENTLY.

666
00:24:06,421 --> 00:24:09,157
SO IT MAY BE THAT THESE STUDIES

667
00:24:09,157 --> 00:24:12,661
WERE NOT INTERVENING AT THE

668
00:24:12,661 --> 00:24:15,497
IDEAL CLINICAL TIME POINT.

669
00:24:15,497 --> 00:24:17,266
SO COULD IT BE THAT ANTIBODIES

670
00:24:17,266 --> 00:24:20,002
AT ART INITIATION OR PERHAPS AT

671
00:24:20,002 --> 00:24:24,806
ARTEART RESUMPTION IS A BETTER E

672
00:24:24,806 --> 00:24:25,907
TO INTERVENE.

673
00:24:25,907 --> 00:24:27,442
SO THIS IS A STUDY THAT BRAD

674
00:24:27,442 --> 00:24:29,511
DISCUSSED A LITTLE EARLIER THAT

675
00:24:29,511 --> 00:24:35,317
WAS CONDUCTED BY OLE SOGA ARD.

676
00:24:35,317 --> 00:24:40,222
, HERE HE ENROLLED INDIVIDUALS

677
00:24:40,222 --> 00:24:41,657
TO RECEIVE -- REVERSING AGENT

678
00:24:41,657 --> 00:24:43,625
AND THE POINT HERE WAS TO SEE IF

679
00:24:43,625 --> 00:24:45,694
THIS INTERVENTION AT ART

680
00:24:45,694 --> 00:24:46,762
INITIATION WOULD INTERFERE WITH

681
00:24:46,762 --> 00:24:47,796
THE ESTABLISHMENT OF THE

682
00:24:47,796 --> 00:24:48,664
RESERVOIR.

683
00:24:48,664 --> 00:24:51,166
SO THE INTERVENTION TOOK PLACE

684
00:24:51,166 --> 00:24:54,002
OVER SEVERAL WEEKS, AND THEN THE

685
00:24:54,002 --> 00:24:55,304
PARTICIPANTS WENT OFF ART AT THE

686
00:24:55,304 --> 00:24:56,305
END OF ONE YEAR.

687
00:24:56,305 --> 00:24:57,306
WHAT'S INTERESTING IN THIS STUDY

688
00:24:57,306 --> 00:24:59,174
IS THAT THE PARTICIPANTS THAT

689
00:24:59,174 --> 00:25:02,044
RECEIVED THE ANTIBODY WITH OR

690
00:25:02,044 --> 00:25:04,313
WITHOUT -- BUT HAD SENSITIVE

691
00:25:04,313 --> 00:25:05,113
NEUTRALIZATION SENSITIVE VIRUSES

692
00:25:05,113 --> 00:25:07,416
AT THE START, SO PLASMA VIRUSES

693
00:25:07,416 --> 00:25:08,684
THAT WERE SENSITIVE TO THE

694
00:25:08,684 --> 00:25:11,219
ANTIBODY, THEY MAINTAINED HIGHER

695
00:25:11,219 --> 00:25:12,721
CD8 T-CELL RESPONSES THAN THE

696
00:25:12,721 --> 00:25:14,923
OTHER GROUPS PRIOR TO ART DISTIN

697
00:25:14,923 --> 00:25:17,893
WAITION.

698
00:25:17,893 --> 00:25:18,994
DISCONTINUATION.

699
00:25:18,994 --> 00:25:20,462
THEY ALSO EXPERIENCED VIRAL

700
00:25:20,462 --> 00:25:21,596
REBOUND THAT WAS DELAYED AND

701
00:25:21,596 --> 00:25:23,131
THEN SHOW THE DIFFERENT VIRAL

702
00:25:23,131 --> 00:25:25,200
DYNAMIC WHEN ART WAS

703
00:25:25,200 --> 00:25:26,868
DISCONTINUED IN COMPARISON TO

704
00:25:26,868 --> 00:25:28,603
INDIVIDUALS WHO HAD RESISTANT

705
00:25:28,603 --> 00:25:29,671
VIRUSES.

706
00:25:29,671 --> 00:25:34,843
SO IT SEEMS THERE'S A SHIFT IN

707
00:25:34,843 --> 00:25:36,912
HOW -- THE INTERFACE BETWEEN

708
00:25:36,912 --> 00:25:38,013
IMMUNE RESPONSES AND VIRUSES

709
00:25:38,013 --> 00:25:40,315
AFTER INTERVENTION.

710
00:25:40,315 --> 00:25:42,250
SO WHEN WE LOOK ACROSS THE

711
00:25:42,250 --> 00:25:45,087
STUDIES THAT WE HAVE COMPLETED,

712
00:25:45,087 --> 00:25:46,655
WE SEE THE ANTIBODIES MAINTAIN

713
00:25:46,655 --> 00:25:48,623
SUPPRESSION, WE HAVE THESE

714
00:25:48,623 --> 00:25:50,025
INDICATIONS THAT PERHAPS THERE

715
00:25:50,025 --> 00:25:51,893
IS INTERFERENCE WITH HIV

716
00:25:51,893 --> 00:25:53,095
PERSISTENCE, AND ACROSS THESE

717
00:25:53,095 --> 00:25:56,264
TRIALS, WE HAVE IDENTIFIED SIX

718
00:25:56,264 --> 00:25:58,767
FULL OR PARTIAL POST

719
00:25:58,767 --> 00:25:59,868
INTERVENTION CONTROLLERS, BUT WE

720
00:25:59,868 --> 00:26:01,970
DON'T REALLY -- ASIDE OF THESE

721
00:26:01,970 --> 00:26:03,372
CHANGES IN T-CELL RESPONSES, WE

722
00:26:03,372 --> 00:26:04,706
DON'T REALLY HAVE A GOOD

723
00:26:04,706 --> 00:26:07,442
UNDERSTANDING OF WHAT REALLY

724
00:26:07,442 --> 00:26:08,477
DISTINGUISHING THEM FROM THE

725
00:26:08,477 --> 00:26:11,913
ONES THAT WERE NON-CONTROLLERS.

726
00:26:11,913 --> 00:26:16,718
SO AS BRAD TALKED EARLIER, WE

727
00:26:16,718 --> 00:26:18,687
NOW ARE ALWAYS COMING OFFICIALLY

728
00:26:18,687 --> 00:26:20,122
INTO THE COLLABORATORY AND WHAT

729
00:26:20,122 --> 00:26:21,556
HE'S GOING TO BE FOCUSING ON IS

730
00:26:21,556 --> 00:26:25,260
TO TRY TO UNDERSTAND THIS POST

731
00:26:25,260 --> 00:26:27,129
INTERVENTION CONTROL OF

732
00:26:27,129 --> 00:26:29,297
PARTICIPANTS THAT PARTICIPATE IN

733
00:26:29,297 --> 00:26:31,066
OUR STUDIES AND HE'S GOING TO DO

734
00:26:31,066 --> 00:26:33,001
THAT BY APPLYING A SERIES OF

735
00:26:33,001 --> 00:26:34,569
MULTI-OMIC APPROACHES THAT ARE

736
00:26:34,569 --> 00:26:36,171
GOING TO -- AIMING TO

737
00:26:36,171 --> 00:26:37,672
CHARACTERIZE IMMUNE RESPONSES AT

738
00:26:37,672 --> 00:26:39,708
THE TRANSCRIPTOMIC AND PHENOTYPE

739
00:26:39,708 --> 00:26:41,643
LEVEL TO TRY TO UNCOVER PERHAPS

740
00:26:41,643 --> 00:26:44,946
WHAT FEATURES ARE ARE

741
00:26:44,946 --> 00:26:47,215
DISTINGUISHED CONTROLLERS FROM

742
00:26:47,215 --> 00:26:49,317
NON-CONTROLLERS.

743
00:26:49,317 --> 00:26:51,953
SO WE ALSO HAVE AN ONGOING

744
00:26:51,953 --> 00:26:53,688
STUDY, THE CLINICAL TRIAL IS

745
00:26:53,688 --> 00:26:54,656
FUNDED BY THE GATES FOUNDATION

746
00:26:54,656 --> 00:26:57,726
THROUGH THE FRONTIERS PROGRAM.

747
00:26:57,726 --> 00:27:00,762
THE STUDY IS BEING CONDUCTED IN

748
00:27:00,762 --> 00:27:06,935
THE UK WITH FIDLER AND FRATER.

749
00:27:06,935 --> 00:27:09,538
IT'S A PLACEBO CONTROLLED RAND

750
00:27:09,538 --> 00:27:11,106
DOMMIZED STUDY WHERE INDIVIDUALS

751
00:27:11,106 --> 00:27:13,275
STARTED ART DURING EARLY

752
00:27:13,275 --> 00:27:15,143
INFECTION, RANDOMIZED 1 TO 1 TO

753
00:27:15,143 --> 00:27:16,778
EITHER RECEIVE AN INFUSION OF

754
00:27:16,778 --> 00:27:21,783
THE TWO ANTIBODIES OR PLACEBO.

755
00:27:21,783 --> 00:27:23,084
AND THEY DISCONTINUED ART TWO

756
00:27:23,084 --> 00:27:23,885
DAYS LATER.

757
00:27:23,885 --> 00:27:25,187
SOME OF THE PARTICIPANTS RECEIVE

758
00:27:25,187 --> 00:27:27,389
A SECOND DOSE OF THE ANTIBODY IF

759
00:27:27,389 --> 00:27:28,323
THEY CONTINUE TO MAINTAIN

760
00:27:28,323 --> 00:27:29,458
SUPPRESSION.

761
00:27:29,458 --> 00:27:30,792
THE STUDY -- THE GOALS OF THE

762
00:27:30,792 --> 00:27:33,161
STUDY IS TO SEE, NUMBER ONE, IF

763
00:27:33,161 --> 00:27:34,729
THERE IS MAINTENANCE OF

764
00:27:34,729 --> 00:27:37,232
SUPPRESSION LONG TERM WITH THIS

765
00:27:37,232 --> 00:27:37,999
LONG-ACTING ANTIBODIES IN

766
00:27:37,999 --> 00:27:39,734
COMPARISON TO PLACEBO.

767
00:27:39,734 --> 00:27:41,503
AND THEN I'LL TALK ABOUT THE

768
00:27:41,503 --> 00:27:43,138
MORE EXPLORATORY ARM OF THE

769
00:27:43,138 --> 00:27:43,572
STUDY.

770
00:27:43,572 --> 00:27:45,774
THE STUDY IS DESIGNED TO ENROLL

771
00:27:45,774 --> 00:27:47,509
A TOTAL OF 72 PARTICIPANTS.

772
00:27:47,509 --> 00:27:49,711
SO FAR 60 HAVE BEEN DOSED AND

773
00:27:49,711 --> 00:27:52,981
THEN OUT OF THOSE, 37 HAVE BEEN

774
00:27:52,981 --> 00:27:54,182
UNBLINDED, BUT THIS FIRST PHASE

775
00:27:54,182 --> 00:27:56,251
OF THE STUDY REMAINS BLINDED.

776
00:27:56,251 --> 00:27:58,019
SO WE WON'T BE TALKING FURTHER

777
00:27:58,019 --> 00:28:00,989
ABOUT THIS.

778
00:28:00,989 --> 00:28:03,258
BUT WE HAVE STARTED TO DO

779
00:28:03,258 --> 00:28:06,294
ANALYSIS ON THE GROUP B STAGE

780
00:28:06,294 --> 00:28:07,095
TWO PHASE OF THE STUDY.

781
00:28:07,095 --> 00:28:08,730
SO AGAIN, PARTICIPANTS COME IN,

782
00:28:08,730 --> 00:28:10,932
THEY RECEIVE PLACEBO,

783
00:28:10,932 --> 00:28:13,001
DISCONTINUE ART.

784
00:28:13,001 --> 00:28:15,670
ONCE ART -- ARE MET, THEN WE

785
00:28:15,670 --> 00:28:17,472
KNOW THEY ARE UNBLINDED, THE

786
00:28:17,472 --> 00:28:19,007
ONES THAT DID RECEIVE PLACEBO

787
00:28:19,007 --> 00:28:21,743
ARE OFFERED TO RECEIVE AN

788
00:28:21,743 --> 00:28:23,378
INFUSION OF THE TWO ANTIBODIES.

789
00:28:23,378 --> 00:28:24,913
THE PROTOCOL WAS SUBSEQUENTLY

790
00:28:24,913 --> 00:28:27,449
CHANGED TO OFFER -- TO HAVE A

791
00:28:27,449 --> 00:28:31,486
SECOND DOSE AT 20 WEEKS LATER.

792
00:28:31,486 --> 00:28:33,321
SO THE INFUSION IS GIVEN

793
00:28:33,321 --> 00:28:36,191
TOGETHER WITH ART RESTART.

794
00:28:36,191 --> 00:28:37,392
SIX MONTHS AFTER THE INFUSIONS

795
00:28:37,392 --> 00:28:38,460
ARE GIVEN THEY COME OFF OF ART

796
00:28:38,460 --> 00:28:40,128
FOR A SECOND TIME AND THEY ARE

797
00:28:40,128 --> 00:28:42,864
MONITORED UNTIL VIRAL REBOWP.

798
00:28:42,864 --> 00:28:43,298
 REBOUND.

799
00:28:43,298 --> 00:28:44,833
I SHOULD ALSO SAY THE

800
00:28:44,833 --> 00:28:47,569
PARTICIPANTS WERE SELECTED FOR

801
00:28:47,569 --> 00:28:49,971
SENSITIVITY AT LEAST AT A

802
00:28:49,971 --> 00:28:52,807
SEQUENCE LEVEL TO 1074.

803
00:28:52,807 --> 00:28:54,009
SO IN THIS OPEN LABEL PHASE OF

804
00:28:54,009 --> 00:28:55,577
THE STUDY THERE ARE ONGOING

805
00:28:55,577 --> 00:28:57,846
ANALYSIS OF THE RESERVOIR

806
00:28:57,846 --> 00:29:01,783
REBOUND VIRUSES.

807
00:29:01,783 --> 00:29:03,585
HERE I'M JUST GOING TO SHARE TWO

808
00:29:03,585 --> 00:29:04,853
EXAMPLES TO ILLUSTRATE WHAT

809
00:29:04,853 --> 00:29:05,720
WE'RE STARTING TO SEE.

810
00:29:05,720 --> 00:29:09,658
SO IN THIS FIRST PARTICIPANT,

811
00:29:09,658 --> 00:29:11,927
HERE I'M SHOWING THE VIRAL LOAD

812
00:29:11,927 --> 00:29:13,495
CURVES ANTIBODY LEVELS OVER

813
00:29:13,495 --> 00:29:13,728
TIME.

814
00:29:13,728 --> 00:29:16,097
AND THEN THE TIME POINTS WHERE

815
00:29:16,097 --> 00:29:17,766
SEQUENCING OF ENVELOPE TOOK

816
00:29:17,766 --> 00:29:18,199
PLACE.

817
00:29:18,199 --> 00:29:20,035
SO IF YOU SEE HERE, THIS

818
00:29:20,035 --> 00:29:22,370
PARTICIPANT EXPERIENCED REBOUND,

819
00:29:22,370 --> 00:29:24,739
THIS IS A PLACEBO RECIPIENT,

820
00:29:24,739 --> 00:29:25,974
EXPERIENCED REBOUND WITHIN ABOUT

821
00:29:25,974 --> 00:29:28,143
THREE WEEKS OF DISCONTINUING

822
00:29:28,143 --> 00:29:30,512
ART, VIRAL LOADS REACHED ABOUT

823
00:29:30,512 --> 00:29:31,980
200,000 AND THEN HE WAS

824
00:29:31,980 --> 00:29:34,816
RESTARTED ON ART AND RECEIVED AN

825
00:29:34,816 --> 00:29:37,452
ANTIBODY INFUSION AT THIS TIME.

826
00:29:37,452 --> 00:29:39,588
WAS MAINTAINED ON ART FOR ABOUT

827
00:29:39,588 --> 00:29:41,489
SIX MONTHS, ART WAS DISCONTINUED

828
00:29:41,489 --> 00:29:46,595
DISCONTINUEDTHE SECOND TIME ANDA

829
00:29:46,595 --> 00:29:48,430
RETURNS ABOUT SIX WEEKS AFTER

830
00:29:48,430 --> 00:29:49,397
THE SECOND DISCONTINUATION OF

831
00:29:49,397 --> 00:29:50,832
ART AND A TIME WHEN ANTIBODY

832
00:29:50,832 --> 00:29:53,568
LEVELS WERE ABOUT 20 AND

833
00:29:53,568 --> 00:29:54,769
30-MICROGRAMS PER ML SO THERE'S

834
00:29:54,769 --> 00:29:56,304
STILL SOME ANTIBODY ON BOARD.

835
00:29:56,304 --> 00:29:57,839
BUT UNLIKE WHAT HAPPENED AFTER

836
00:29:57,839 --> 00:29:59,307
THE FIRST ATI PERIOD, HE

837
00:29:59,307 --> 00:30:01,876
REBOUNDS TO A LOWER PEAK LEVEL

838
00:30:01,876 --> 00:30:04,346
VIREMIA AND THEN HIS VIRAL LOADS

839
00:30:04,346 --> 00:30:06,715
FLUCTUATE OVER THIS COURSE OF

840
00:30:06,715 --> 00:30:07,916
ABOUT SIX MONTHS.

841
00:30:07,916 --> 00:30:09,451
ONCE IT STARTS TO BE MORE

842
00:30:09,451 --> 00:30:11,586
PERSISTENT, HE'S CLOSE TO

843
00:30:11,586 --> 00:30:16,558
NEEDING ART -- SO WHAT WE ARE

844
00:30:16,558 --> 00:30:19,294
LEARNING NOW FROM ANALYZING HIS

845
00:30:19,294 --> 00:30:23,465
VIRUS, SO HERE THIS PHYLOGENETIC

846
00:30:23,465 --> 00:30:24,866
TREE SHOWS SEQUENCES OBTAINED

847
00:30:24,866 --> 00:30:27,602
FROM PBMCs AT BASELINE.

848
00:30:27,602 --> 00:30:29,771
BLUE IS THE FIRST REBOUND TIME

849
00:30:29,771 --> 00:30:32,207
POINT AND THEN GREEN AND ORANGE,

850
00:30:32,207 --> 00:30:34,809
THE SECOND ATI OF THE PEAKS OF

851
00:30:34,809 --> 00:30:37,112
VIRAL LOADS.

852
00:30:37,112 --> 00:30:38,647
SO WE SEE THERE ARE DIFFERENT

853
00:30:38,647 --> 00:30:40,615
VIRUSES THAT ARE EMERGING, AND

854
00:30:40,615 --> 00:30:41,950
THE RESERVOIR, THERE WAS

855
00:30:41,950 --> 00:30:43,351
SENSITIVITY TO BOTH ANTIBODIES

856
00:30:43,351 --> 00:30:46,421
BUT THERE WAS ONE CLONE THAT HAD

857
00:30:46,421 --> 00:30:49,691
RESISTANCE TO -- HIGHLIGHTED

858
00:30:49,691 --> 00:30:51,459
HERE IN YELLOW.

859
00:30:51,459 --> 00:30:52,661
THE FIRST REBOUND, A CLONE THAT

860
00:30:52,661 --> 00:30:55,830
HAS PARTIAL OR RESISTANCE TO

861
00:30:55,830 --> 00:30:58,299
3BMC ALSO EMERGES, AND AT THE

862
00:30:58,299 --> 00:30:59,668
SECOND TIME POINT, THERE IS NOW

863
00:30:59,668 --> 00:31:01,069
RESISTANCE TO BOTH ANTIBODIES

864
00:31:01,069 --> 00:31:02,704
BECAUSE PROBABLY DURING THIS

865
00:31:02,704 --> 00:31:04,139
PERIOD OF TIME, THERE WAS

866
00:31:04,139 --> 00:31:06,775
MONOTHERAPY WITH 1074, BECAUSE

867
00:31:06,775 --> 00:31:08,343
WE KNEW -- NOW WE KNOW THAT THE

868
00:31:08,343 --> 00:31:11,246
PERSON HAD RESISTANCE TO 3BNC

869
00:31:11,246 --> 00:31:14,049
THAT SELECTED RESISTANCE TO

870
00:31:14,049 --> 00:31:14,315
1074.

871
00:31:14,315 --> 00:31:15,517
BUT WHAT IS INTERESTING HERE

872
00:31:15,517 --> 00:31:16,851
THAT DESPITE NOW HAVING

873
00:31:16,851 --> 00:31:18,253
RESISTANCE TO BOTH ANTIBODIES,

874
00:31:18,253 --> 00:31:20,955
THE VIRAL LOADS CONTINUE, THEY

875
00:31:20,955 --> 00:31:23,825
ARE NOT REACHING THE SAME LEVEL

876
00:31:23,825 --> 00:31:28,329
OF VIREMIA, OF REPLICATION AS IN

877
00:31:28,329 --> 00:31:30,398
THE FIRST ATI PERIOD.  SO WE

878
00:31:30,398 --> 00:31:32,233
DON'T KNOW IF DESPITE HAVING

879
00:31:32,233 --> 00:31:33,101
NEUTRALIZATION RESISTANCE,

880
00:31:33,101 --> 00:31:34,169
PERHAPS THE ANTIBODIES STILL

881
00:31:34,169 --> 00:31:35,570
HAVE A PARTIAL EFFECT, PERHAPS

882
00:31:35,570 --> 00:31:39,274
THESE VIRUSES ARE LESS FIT OR

883
00:31:39,274 --> 00:31:40,241
DURING THIS PERIOD OF TIME,

884
00:31:40,241 --> 00:31:41,976
THERE IS AN ENGAGEMENT OF HOST,

885
00:31:41,976 --> 00:31:43,645
CELL OR -- IMMUNE RESPONSES THAT

886
00:31:43,645 --> 00:31:45,714
ARE SOMEHOW MODIFYING THIS VIRAL

887
00:31:45,714 --> 00:31:48,249
REBOUND DYNAMIC.

888
00:31:48,249 --> 00:31:49,384
THIS IS THE SECOND EXAMPLE.

889
00:31:49,384 --> 00:31:52,287
THIS OTHER PARTICIPANT AGAIN

890
00:31:52,287 --> 00:31:54,022
DISCONTINUES ART, EXPERIENCES

891
00:31:54,022 --> 00:31:55,557
VIRAL REBOUND WITHIN ABOUT THREE

892
00:31:55,557 --> 00:31:59,961
WEEKS OF ART DISCONTINUATION.

893
00:31:59,961 --> 00:32:01,896
HIS PEAK VIREMIA IS LESS THAN

894
00:32:01,896 --> 00:32:03,364
10,000.

895
00:32:03,364 --> 00:32:05,166
HE RESUMES ART AFTER A PERIOD OF

896
00:32:05,166 --> 00:32:08,269
SIX WEEKS OF VIRAL LOADS ABOVE

897
00:32:08,269 --> 00:32:12,774
1,000, RECEIVES THE ANTIBODY

898
00:32:12,774 --> 00:32:13,508
WHILE ON ART.

899
00:32:13,508 --> 00:32:14,943
ART IS DISCONTINUED SIX MONTHS

900
00:32:14,943 --> 00:32:16,478
LATER.

901
00:32:16,478 --> 00:32:18,346
VIRAL REBOUND LIKE THE OTHER

902
00:32:18,346 --> 00:32:20,415
PARTICIPANT STARTS TO EMERGE AT

903
00:32:20,415 --> 00:32:22,951
ABOUT SIX WEEKS AFTER THE ART IS

904
00:32:22,951 --> 00:32:23,284
DISCONTINUED.

905
00:32:23,284 --> 00:32:24,886
IN THIS CASE, THE ANTIBODY

906
00:32:24,886 --> 00:32:30,658
LEVELS WERE ABOUT 50 MI CROW 50S

907
00:32:30,658 --> 00:32:31,359
PER ML.

908
00:32:31,359 --> 00:32:32,627
ONCE AGAIN THE VIRAL LOAD

909
00:32:32,627 --> 00:32:33,895
DOESN'T REACH THE SAME LEVEL OF

910
00:32:33,895 --> 00:32:36,064
PEAK AS IN THE FIRST ATI.

911
00:32:36,064 --> 00:32:37,799
HERE LEVELS ARE ABOUT 200 TO

912
00:32:37,799 --> 00:32:38,333
300.

913
00:32:38,333 --> 00:32:39,667
THESE VIRAL LOADS GO UP AND DOWN

914
00:32:39,667 --> 00:32:41,302
FOR A PERIOD OF SIX MONTHS, AND

915
00:32:41,302 --> 00:32:43,271
THEN HE FULLY SUPPRESSES AND

916
00:32:43,271 --> 00:32:45,240
THEN CONTINUES TO DO SO NOW FOR

917
00:32:45,240 --> 00:32:46,474
ABOUT 14 MONTHS AFTER THE SECOND

918
00:32:46,474 --> 00:32:48,309
TIME THE ART WAS DISCONTINUED.

919
00:32:48,309 --> 00:32:52,247
WE DON'T HAVE THE ENTIRE AND

920
00:32:52,247 --> 00:32:54,849
BODY PK CURVE YET AND WE DON'T

921
00:32:54,849 --> 00:32:56,518
HAVE THE SENSITIVITY RESULTS FOR

922
00:32:56,518 --> 00:32:58,386
THE REBOUND VIRUSES.

923
00:32:58,386 --> 00:33:02,223
BUT THE SEQUENCES OF THE

924
00:33:02,223 --> 00:33:05,293
RESERVOIR VIRUSES IN FIRST

925
00:33:05,293 --> 00:33:06,795
REBOUND THAT WERE THEN SELECTED

926
00:33:06,795 --> 00:33:10,031
FOR TESTING WITH NEUTRALIZATION

927
00:33:10,031 --> 00:33:11,199
SHOWS SENSITIVITY TO BOTH

928
00:33:11,199 --> 00:33:11,499
ANTIBODIES.

929
00:33:11,499 --> 00:33:12,934
IN ADDITION WHAT WE ARE ALSO

930
00:33:12,934 --> 00:33:14,035
LEARNING FROM THIS PARTICIPANT,

931
00:33:14,035 --> 00:33:15,570
AND THIS IS WORK THAT WAS DONE

932
00:33:15,570 --> 00:33:18,540
IN JOHN'S LAB, WE'RE STARTING TO

933
00:33:18,540 --> 00:33:20,341
LOOK AT HIS T-CELL RESPONSES,

934
00:33:20,341 --> 00:33:22,677
AND IN THIS GRAPH HERE IT'S

935
00:33:22,677 --> 00:33:26,281
SHOWING LONGITUDALLY CHANGES

936
00:33:26,281 --> 00:33:28,917
IN -- SO CD8 T-CELLS TO

937
00:33:28,917 --> 00:33:30,985
DIFFERENT HIV GENES, AND IN

938
00:33:30,985 --> 00:33:32,387
PURPLE HERE IS THE VIRAL LOAD

939
00:33:32,387 --> 00:33:35,690
CURVE AND THEN HERE ARE THE

940
00:33:35,690 --> 00:33:37,559
DIFFERENT T-CELL RESPONSES.

941
00:33:37,559 --> 00:33:41,262
AND AS EXPECTED, FOLLOWING THE

942
00:33:41,262 --> 00:33:42,697
FIRST VIRAL REBOUND, THERE IS AN

943
00:33:42,697 --> 00:33:46,301
INCREASE IN T-CELL RESPONSES,

944
00:33:46,301 --> 00:33:47,836
THAT THOSE RESPONSES DECREASE

945
00:33:47,836 --> 00:33:50,672
WHEN ART IS RESUMED AND THE

946
00:33:50,672 --> 00:33:51,873
PERSON ACHIEVES VIRAL

947
00:33:51,873 --> 00:33:52,340
SUPPRESSION.

948
00:33:52,340 --> 00:33:54,642
ONCE AGAIN, THE T-CELLS START TO

949
00:33:54,642 --> 00:33:57,478
COME UP AFTER THE SECOND PERIOD

950
00:33:57,478 --> 00:33:59,581
OF VIREMIA, BUT WHAT'S

951
00:33:59,581 --> 00:34:00,882
INTERESTING HERE, EVEN 20 WEEKS

952
00:34:00,882 --> 00:34:03,518
OR SO AFTER THE PERSON

953
00:34:03,518 --> 00:34:06,888
RESUPPRESSES ON HIS OWN, THESE

954
00:34:06,888 --> 00:34:07,889
T-CELL RESPONSES REMAIN

955
00:34:07,889 --> 00:34:08,423
ELEVATED.

956
00:34:08,423 --> 00:34:10,525
WE DON'T KNOW IF THIS IS GOING

957
00:34:10,525 --> 00:34:12,160
TO INCLUDE THE -- BECAUSE LATER

958
00:34:12,160 --> 00:34:13,561
TIME POINTS HAVEN'T BEEN DONE

959
00:34:13,561 --> 00:34:14,529
YET BUT WE FIND IT INTERESTING

960
00:34:14,529 --> 00:34:16,231
THAT IT SEEMS THAT IN THIS CASE,

961
00:34:16,231 --> 00:34:17,532
UNLIKE WHAT WE HAD SEEN IN OUR

962
00:34:17,532 --> 00:34:19,167
EARLIER STUDY, THIS CHANGE IN

963
00:34:19,167 --> 00:34:21,669
T-CELL RESPONSES ARE PERSISTING,

964
00:34:21,669 --> 00:34:23,004
THEY'RE NOT AS TRANSIENT AS IN

965
00:34:23,004 --> 00:34:26,441
OUR EARLIER STUDY.

966
00:34:26,441 --> 00:34:27,842
THEN THE LAST THING I WANT TO

967
00:34:27,842 --> 00:34:29,244
SHARE IS THAT WE ALSO HAVE A

968
00:34:29,244 --> 00:34:32,213
STUDY THAT IS FUNDED THROUGH

969
00:34:32,213 --> 00:34:33,314
A -- MECHANISM THAT IS ONGOING.

970
00:34:33,314 --> 00:34:38,019
THIS IS AGAIN THE COMBINATION OF

971
00:34:38,019 --> 00:34:40,755
3BNC AND 1074 PROVIDED BY OUR

972
00:34:40,755 --> 00:34:45,460
PARTNER IMMUNITY BU BIO.

973
00:34:45,460 --> 00:34:47,528
IT'S AN OPEN LABEL SINGLE ARM

974
00:34:47,528 --> 00:34:50,498
STUDY WHERE WE ADMINISTER THE

975
00:34:50,498 --> 00:34:53,034
ANTIBODIES, THE INTERVENTION

976
00:34:53,034 --> 00:34:55,203
PERIOD IS OVER A PERIOD OF SIX

977
00:34:55,203 --> 00:34:58,706
MONTHS DURING ATI SO ART IS

978
00:34:58,706 --> 00:35:00,341
DISCONTINUED RIGHT AFTER THE

979
00:35:00,341 --> 00:35:01,776
ANTIBODY INFUSIONS AND THEY'RE

980
00:35:01,776 --> 00:35:02,877
MONITORED UNTIL REBOUND.

981
00:35:02,877 --> 00:35:03,878
THE END POINTS ARE VIRAL

982
00:35:03,878 --> 00:35:06,714
SUPPRESSION BY WEEK 24, BUT ALSO

983
00:35:06,714 --> 00:35:08,049
WHAT'S MOST -- WHAT WE ARE MOST

984
00:35:08,049 --> 00:35:09,050
INTERESTED TO SEE IS WHAT

985
00:35:09,050 --> 00:35:11,686
HAPPENS DURING THIS PERIOD OF

986
00:35:11,686 --> 00:35:13,888
BNAB -- OR BEYOND THE BNAB

987
00:35:13,888 --> 00:35:16,391
WASHOUT PERIOD, ARE WE GOING TO

988
00:35:16,391 --> 00:35:18,159
ABLE TO ACHIEVE VIROLOGIC

989
00:35:18,159 --> 00:35:18,493
CONTROL.

990
00:35:18,493 --> 00:35:20,361
WE NOW HAVE THOSE 17

991
00:35:20,361 --> 00:35:20,895
PARTICIPANTS.

992
00:35:20,895 --> 00:35:21,996
EIGHT ARE STILL IN THE

993
00:35:21,996 --> 00:35:23,398
INTERVENTION PERIOD, FOUR HAVE

994
00:35:23,398 --> 00:35:25,066
PROGRESSED INTO THE LONG-TERM

995
00:35:25,066 --> 00:35:28,436
FOLLOW-UP OF ART, AND THEN FOUR

996
00:35:28,436 --> 00:35:30,872
HAD MET ART -- CRITERIA AND ARE

997
00:35:30,872 --> 00:35:31,673
IN STEP THREE.

998
00:35:31,673 --> 00:35:36,945
WE HAVE NOW GIVEN 87 DOSES OF  

999
00:35:36,945 --> 00:35:37,979
N-803.

1000
00:35:37,979 --> 00:35:39,547
IN GENERAL PARTICIPANTS HAVE

1001
00:35:39,547 --> 00:35:40,415
EXPERIENCED WHAT'S BEEN

1002
00:35:40,415 --> 00:35:41,716
DESCRIBED IN THE PAST, LOCAL

1003
00:35:41,716 --> 00:35:43,251
INJECTION REACTIONS THAT HAVE

1004
00:35:43,251 --> 00:35:44,686
BEEN OF GRADE # AND 2.

1005
00:35:44,686 --> 00:35:46,754
ONE EXPERIENCED GRADE 3 MYALGIA

1006
00:35:46,754 --> 00:35:48,756
AND NOW HE REMAINS ON STUDY BUT

1007
00:35:48,756 --> 00:35:50,692
HE'S GOING TO RECEIVE REDUCED

1008
00:35:50,692 --> 00:35:52,660
DOSES OF N-803.

1009
00:35:52,660 --> 00:35:54,662
SO HOPEFULLY WE'LL HAVE DATA TO

1010
00:35:54,662 --> 00:35:55,530
SHARE WITH YOU NEXT TIME WE

1011
00:35:55,530 --> 00:35:55,964
MEET.

1012
00:35:55,964 --> 00:35:57,565
SO TO SUMMARIZE, THESE STUDIES

1013
00:35:57,565 --> 00:36:01,235
OF PASSIVELY ADMINISTERED

1014
00:36:01,235 --> 00:36:02,870
ANTIBODIES SHOW THERE SEEMS TO

1015
00:36:02,870 --> 00:36:06,808
BE SOME EFFECT ON -- BUT WE

1016
00:36:06,808 --> 00:36:07,909
HAVEN'T BEEN ABLE TO CLEARLY

1017
00:36:07,909 --> 00:36:10,111
DETERMINE IF THIS IS DUE TO A

1018
00:36:10,111 --> 00:36:11,746
VACCINAL EFFECT BUT PERHAPS MORE

1019
00:36:11,746 --> 00:36:12,413
IMPORTANTLY, THESE EFFECTS HAVE

1020
00:36:12,413 --> 00:36:15,016
NOT BEEN SUFFICIENT TO MEDIATE

1021
00:36:15,016 --> 00:36:16,784
LONG TERM VIROLOGIC CONTROL AT

1022
00:36:16,784 --> 00:36:17,418
LEAST CONSISTENTLY.

1023
00:36:17,418 --> 00:36:18,653
ALL OF THESE STUDIES HAVE BEEN

1024
00:36:18,653 --> 00:36:21,723
SMALL TO DATE.

1025
00:36:21,723 --> 00:36:23,057
RIO IS GOING TO BE A BIG STUDY

1026
00:36:23,057 --> 00:36:24,926
WHERE WE HAVE DATA FROM

1027
00:36:24,926 --> 00:36:25,293
72 PARTICIPANTS.

1028
00:36:25,293 --> 00:36:26,894
SO WE HOPE THAT WE WILL BE

1029
00:36:26,894 --> 00:36:28,096
LEARNING QUITE A BIT FROM THAT

1030
00:36:28,096 --> 00:36:30,164
STUDY.

1031
00:36:30,164 --> 00:36:33,034
BUT EVEN IN THEE FEW STUDIES, WE

1032
00:36:33,034 --> 00:36:35,970
WERE ABLE TO IDENTIFY SOME POST

1033
00:36:35,970 --> 00:36:36,738
INTERVENTIONAL CONTROLLERS AND

1034
00:36:36,738 --> 00:36:37,839
NOW GOING FORWARD, WE ARE GOING

1035
00:36:37,839 --> 00:36:39,374
TO ANALYZE IN GREATER DETAIL

1036
00:36:39,374 --> 00:36:40,908
USING DIFFERENT APPROACHES, SO

1037
00:36:40,908 --> 00:36:42,443
THAT WITH THE HOPE THAT WE'RE

1038
00:36:42,443 --> 00:36:44,545
GOING TO UNCOVER DIFFERENT

1039
00:36:44,545 --> 00:36:46,948
MECHANISMS OF CONTROL THAT COULD

1040
00:36:46,948 --> 00:36:49,384
HELP US SELECT OR REFINE FUTURE

1041
00:36:49,384 --> 00:36:51,019
CURE STRATEGIES.

1042
00:36:51,019 --> 00:36:53,121
AND THEN ANOTHER PART OF RF

1043
00:36:53,121 --> 00:36:54,122
2 THAT I DIDN'T HAVE TIME TO

1044
00:36:54,122 --> 00:36:55,857
TALK ABOUT, WHICH IS WORK THAT

1045
00:36:55,857 --> 00:36:59,027
HAS BEEN DONE BY UNIVERSITY OF

1046
00:36:59,027 --> 00:37:01,662
PITTSBURGH WITH AYA LI, IT'S

1047
00:37:01,662 --> 00:37:04,632
VERY CLEAR THAT ONE OF THE CHAL

1048
00:37:04,632 --> 00:37:06,701
CHALLENGES WITH BNAB IS IMMUNE

1049
00:37:06,701 --> 00:37:07,135
ESCAPE.

1050
00:37:07,135 --> 00:37:09,337
SO THEY'RE WORKING WITH NOVEL

1051
00:37:09,337 --> 00:37:10,671
THERAPEUTIC TOOLS TO PREVENT

1052
00:37:10,671 --> 00:37:11,873
IMMUNE ESCAPE IN ORDER TO

1053
00:37:11,873 --> 00:37:13,074
ACHIEVE VIROLOGIC CONTROL, AND

1054
00:37:13,074 --> 00:37:14,942
THEN TO DO THAT, THAT THEY'RE

1055
00:37:14,942 --> 00:37:18,012
DEVELOPING DIFFERENT BI AND

1056
00:37:18,012 --> 00:37:20,048
TRI-SPECIFIC MOLECULES THAT ARE

1057
00:37:20,048 --> 00:37:21,749
NOT ONLY ENGAGED WITH THE

1058
00:37:21,749 --> 00:37:23,051
ENVELOPE BUT ALSO EFFECTOR

1059
00:37:23,051 --> 00:37:23,251
CELLS.

1060
00:37:23,251 --> 00:37:25,787
WITH THAT I'LL ACKNOWLEDGE OUR

1061
00:37:25,787 --> 00:37:26,788
STUDY PARTICIPANTS THAT ENROLL

1062
00:37:26,788 --> 00:37:28,322
IN THESE VERY COMPLEX STUDIES

1063
00:37:28,322 --> 00:37:32,360
AND OUR VARIOUS COLLABORATORS,

1064
00:37:32,360 --> 00:37:34,562
ESPECIALLY ELE AND THEN JOHN.

1065
00:37:34,562 --> 00:37:35,029
THANK YOU.

1066
00:37:35,029 --> 00:37:42,570
[APPLAUSE]

1067
00:37:42,570 --> 00:37:44,872
>> RF 3 WE'RE FOCUSED ON

1068
00:37:44,872 --> 00:37:46,941
DIFFERENT WAYS BY WHICH INFECTED

1069
00:37:46,941 --> 00:37:49,777
CELLS MIGHT RESIST BEING KILLED,

1070
00:37:49,777 --> 00:37:51,646
SO THE SUMMARY IS WE'RE ASKING

1071
00:37:51,646 --> 00:37:53,214
THE QUESTION DO SOME HIV

1072
00:37:53,214 --> 00:37:54,515
INFECTED CELLS HAVE WAYS OF

1073
00:37:54,515 --> 00:37:55,817
PROTECTING THEMSELVES FROM BEING

1074
00:37:55,817 --> 00:37:57,251
KILLED, EVEN WHEN SEEN BY THE

1075
00:37:57,251 --> 00:37:57,919
IMMUNE SYSTEM?

1076
00:37:57,919 --> 00:38:01,322
WE FIND THAT YES, IMMUNE

1077
00:38:01,322 --> 00:38:04,926
RESISTANT POPULATIONS EXIST AND

1078
00:38:04,926 --> 00:38:06,994
NOW WE WANT TO OVERCOME THESE TO

1079
00:38:06,994 --> 00:38:08,663
ELIMINATE THE HIV RESERVOIR.

1080
00:38:08,663 --> 00:38:10,631
SO HERE'S HOW WE TEST TO SEE IF

1081
00:38:10,631 --> 00:38:12,166
SOME CELLS ARE RESISTANT TO

1082
00:38:12,166 --> 00:38:13,267
KILLING.

1083
00:38:13,267 --> 00:38:14,569
WE HAVE CELLS THAT ARE INFECTED

1084
00:38:14,569 --> 00:38:16,237
WITH EITHER A WILD TYPE HIV OR

1085
00:38:16,237 --> 00:38:19,607
AN HIV THAT HAS ONE POINT

1086
00:38:19,607 --> 00:38:21,142
MUTATION AND EPITOPE TARGETED BY

1087
00:38:21,142 --> 00:38:22,343
A T-CELL CLONE.

1088
00:38:22,343 --> 00:38:23,578
WE MIX THESE TOGETHER,

1089
00:38:23,578 --> 00:38:24,645
CO-CULTURE WITH THE T-CELL CLONE

1090
00:38:24,645 --> 00:38:25,746
THAT'S GOING TO TARGET THOSE

1091
00:38:25,746 --> 00:38:27,748
CELLS INFECTED WITH WILD TYPE

1092
00:38:27,748 --> 00:38:29,050
HIV, AND WE'RE GOING TO

1093
00:38:29,050 --> 00:38:30,918
POTENTIALLY SELECT FOR RESISTANT

1094
00:38:30,918 --> 00:38:31,352
POPULATION.

1095
00:38:31,352 --> 00:38:33,788
WE THEN COME IN WITH A SECOND

1096
00:38:33,788 --> 00:38:35,089
CTL CLONE THAT TARGETS AN

1097
00:38:35,089 --> 00:38:37,391
EPITOPE THAT'S INTACT IN BOTH

1098
00:38:37,391 --> 00:38:39,127
VIRUSES, SO IF THERE'S NO SUCH

1099
00:38:39,127 --> 00:38:40,895
THING AS CTL RESISTANCE IN THE

1100
00:38:40,895 --> 00:38:42,430
FIRST ROUND, WE'LL KILL OFF THE

1101
00:38:42,430 --> 00:38:44,298
WILD TYPE CELLS, AND IN THE

1102
00:38:44,298 --> 00:38:45,700
SECOND ROUND, WE'LL KILL BOTH

1103
00:38:45,700 --> 00:38:47,068
THE ONES THAT WEREN'T SELECTED

1104
00:38:47,068 --> 00:38:49,137
AND THE ONES THAT WERE EQUALLY.

1105
00:38:49,137 --> 00:38:50,905
IF THERE WAS A RESISTANT

1106
00:38:50,905 --> 00:38:51,672
POPULATION, THEN WHAT WE'LL SEE

1107
00:38:51,672 --> 00:38:53,641
IS EXACTLY WHAT WE SEE HERE.

1108
00:38:53,641 --> 00:38:55,076
THIS POPULATION THAT SURVIVED

1109
00:38:55,076 --> 00:38:57,278
THE FIRST ROUND OF KILLING ALSO

1110
00:38:57,278 --> 00:38:58,713
SURVIVES THE SECOND ROUND OF

1111
00:38:58,713 --> 00:38:59,814
KILLING, AND THE CELLS THAT

1112
00:38:59,814 --> 00:39:01,883
WEREN'T SELECTED IN THE FIRST

1113
00:39:01,883 --> 00:39:03,684
ROUND ARE KILLED OFF.

1114
00:39:03,684 --> 00:39:06,020
SO THE FIRST MECHANISM WHICH HAS

1115
00:39:06,020 --> 00:39:07,822
BEEN TALKED ABOUT A LOT IN THIS

1116
00:39:07,822 --> 00:39:09,757
MEETING IS BCL2 OVEREXPRESSION.

1117
00:39:09,757 --> 00:39:12,126
I'M GOING TO GO THROUGH THIS

1118
00:39:12,126 --> 00:39:14,095
QUICKLY FOR THE SAKE OF TIME.

1119
00:39:14,095 --> 00:39:15,863
WE SEE IT'S OVEREXPRESSED IN

1120
00:39:15,863 --> 00:39:17,732
CELLS THAT RESIST KILLING AND

1121
00:39:17,732 --> 00:39:19,567
SUBSEQUENTLY OTHER STUDI STUDIEN

1122
00:39:19,567 --> 00:39:22,036
CANCER SEE THIS IN TUMORS THAT

1123
00:39:22,036 --> 00:39:26,741
OVEREXPRESS BCL2.

1124
00:39:26,741 --> 00:39:28,376
THEY'RE IN PRE-CLINICAL AND

1125
00:39:28,376 --> 00:39:29,243
CLINICAL STAGE DEVELOPMENT.

1126
00:39:29,243 --> 00:39:30,678
WHAT REACH IS FOCUSING ON NOW IS

1127
00:39:30,678 --> 00:39:32,013
ADDING TO THIS PIPELINE.

1128
00:39:32,013 --> 00:39:34,515
SO DOING DISCOVERY SCIENCE AND

1129
00:39:34,515 --> 00:39:35,850
FINDING WHAT OTHER MECHANISMS

1130
00:39:35,850 --> 00:39:39,220
MAY BE TARGETABLE THAT WE CAN

1131
00:39:39,220 --> 00:39:40,121
BRING FORWARD INTO THESE

1132
00:39:40,121 --> 00:39:42,323
DIFFERENT APPROACHES.

1133
00:39:42,323 --> 00:39:43,724
SO THIS IS OUR SCHEMA AGAIN FOR

1134
00:39:43,724 --> 00:39:45,059
LOOKING AT RESISTANCE.

1135
00:39:45,059 --> 00:39:46,694
AGAIN WILD TYPE INFECTED CELLS,

1136
00:39:46,694 --> 00:39:48,663
CELLS INFECTED WITH AN ESCAPE

1137
00:39:48,663 --> 00:39:49,964
MUTANT HIV MIXED AND SUBJECTED

1138
00:39:49,964 --> 00:39:52,166
TO CTL KILLING.

1139
00:39:52,166 --> 00:39:53,734
NOW WE'RE USING MULTI-OMIC

1140
00:39:53,734 --> 00:39:54,936
PROFILING TO LOOK AT WHAT'S

1141
00:39:54,936 --> 00:39:56,237
DIFFERENT OF THESE INFECTED

1142
00:39:56,237 --> 00:39:59,540
CELLS THAT SURVIVE KILLING

1143
00:39:59,540 --> 00:40:00,942
VERSUS THESE ESCAPE MUTANT CELLS

1144
00:40:00,942 --> 00:40:03,044
IN THE EXACT SAME ENVIRONMENT

1145
00:40:03,044 --> 00:40:05,580
ALSO INFECTED WITH HIV THAT

1146
00:40:05,580 --> 00:40:07,982
WEREN'T JUST SUBJECT TODAY CTL

1147
00:40:07,982 --> 00:40:08,950
PRESSURE.

1148
00:40:08,950 --> 00:40:10,384
WE'RE SORT ON CELLS THAT EXPRESS

1149
00:40:10,384 --> 00:40:11,285
ENVELOPE BECAUSE WE'RE NOT

1150
00:40:11,285 --> 00:40:12,486
LOOKING AT LATENCY HERE, WE'RE

1151
00:40:12,486 --> 00:40:13,821
JUST LOOKING AT MECHANISMS BY

1152
00:40:13,821 --> 00:40:16,324
WHICH SOME CELLS CAN SURVIVE

1153
00:40:16,324 --> 00:40:17,425
KILLING.

1154
00:40:17,425 --> 00:40:20,061
HERE'S THE TRANSCRIPTIONAL PROAT

1155
00:40:20,061 --> 00:40:20,761
FILING.

1156
00:40:20,761 --> 00:40:25,600
WITHOUT ME VWHEN WE ADD CTL, WEE

1157
00:40:25,600 --> 00:40:26,500
TRANSCRIPTIONAL PROFILE OF BOTH

1158
00:40:26,500 --> 00:40:28,236
THE CELLS THAT ARE BEING

1159
00:40:28,236 --> 00:40:29,870
TARGETED AND THE CELLS THAT ARE

1160
00:40:29,870 --> 00:40:30,838
NOT BECAUSE THEY'RE IN AN

1161
00:40:30,838 --> 00:40:33,274
ENVIRONMENT WITH AN ACTIVATED

1162
00:40:33,274 --> 00:40:33,841
CTL.

1163
00:40:33,841 --> 00:40:34,475
WHAT'S IMPORTANT IS THAT THESE

1164
00:40:34,475 --> 00:40:35,576
ARE NOW DIFFERENT FROM EACH

1165
00:40:35,576 --> 00:40:36,010
OTHER.

1166
00:40:36,010 --> 00:40:37,378
AND AGAIN THESE ARE PRETTY

1167
00:40:37,378 --> 00:40:38,779
PRECISE CONTROLS SO THIS IS

1168
00:40:38,779 --> 00:40:40,848
TELLING US ABOUT THE FEATURES OF

1169
00:40:40,848 --> 00:40:44,685
CELLS THAT SURVIVED CTL KILLING.

1170
00:40:44,685 --> 00:40:45,820
THERE'S A LOT OF DIFFERENTIAL

1171
00:40:45,820 --> 00:40:46,988
GENES THAT WE CAN GO AFTER, SO

1172
00:40:46,988 --> 00:40:48,689
WE HAVE THE QUESTION OF WHAT TO

1173
00:40:48,689 --> 00:40:49,857
TACKLE AND AS YOU'LL SEE ONE OF

1174
00:40:49,857 --> 00:40:51,292
THE THINGS THAT WE'RE USING IN

1175
00:40:51,292 --> 00:40:54,262
OUR CRITERIA ARE PATHWAYS THAT

1176
00:40:54,262 --> 00:40:58,966
MAY HAVE THERAPEUTIC RELEVANCE.

1177
00:40:58,966 --> 00:41:00,601
WE ALSO SEE THIS AT THE SINGLE

1178
00:41:00,601 --> 00:41:02,903
CELL LEVEL, SO THIS IS

1179
00:41:02,903 --> 00:41:03,337
TRANSCRIPTOMICS.

1180
00:41:03,337 --> 00:41:04,672
THE SURVIVORS CLUSTER

1181
00:41:04,672 --> 00:41:06,841
DIFFERENTLY THAN THE BYSTANDERS.

1182
00:41:06,841 --> 00:41:08,075
WE THINK THERE'S MULTIPLE

1183
00:41:08,075 --> 00:41:09,310
MECHANISMS BY WHICH CELLS CAN

1184
00:41:09,310 --> 00:41:10,111
RESIST KILLING.

1185
00:41:10,111 --> 00:41:11,479
THIS IS SURFACE PROTEIN

1186
00:41:11,479 --> 00:41:13,014
EXPRESSION, THIS IS ONE OF THE

1187
00:41:13,014 --> 00:41:15,383
CITE-SEQ PANELS WITH 150

1188
00:41:15,383 --> 00:41:16,651
ANTIBODIES, SO YOU CAN SEE

1189
00:41:16,651 --> 00:41:17,752
REALLY HOW DIFFERENT THESE

1190
00:41:17,752 --> 00:41:20,421
SURVIVORS ACTUALLY ARE FROM THE

1191
00:41:20,421 --> 00:41:23,024
BYSTANDERS, REALLY CLUSTERING

1192
00:41:23,024 --> 00:41:23,991
VERY DISTINCT POPULATIONS.

1193
00:41:23,991 --> 00:41:26,560
OUR OLD FREN BCL2, WE SEE IT

1194
00:41:26,560 --> 00:41:28,529
HERE AGAIN, THE CELLS THAT

1195
00:41:28,529 --> 00:41:31,132
SURVIVE KILLING TEND TO

1196
00:41:31,132 --> 00:41:32,166
OVEREXPRESSION BCL2.

1197
00:41:32,166 --> 00:41:35,002
WHAT WE SEE WITH THE SINGLE CELL

1198
00:41:35,002 --> 00:41:38,205
DADATA IS THERE'S HETEROGENEITY

1199
00:41:38,205 --> 00:41:39,407
BUT THERE'S ALSO A LOT OF CELLS

1200
00:41:39,407 --> 00:41:42,143
THAT SURVIVE THAT ARE BCL2-LOW.

1201
00:41:42,143 --> 00:41:43,911
SO NOW WE CAN START TO TEASE

1202
00:41:43,911 --> 00:41:45,913
APART THIS HETEROGENEITY AND ASK

1203
00:41:45,913 --> 00:41:46,947
WHAT OTHER MECHANISMS MIGHT BE

1204
00:41:46,947 --> 00:41:47,848
AT PLAY.

1205
00:41:47,848 --> 00:41:50,518
THE FIRST MECHANISM THAT WE SEE

1206
00:41:50,518 --> 00:41:52,286
POINTS TO BIOPHYSICAL PROPERTIES

1207
00:41:52,286 --> 00:41:53,688
OF THE TARGET CELL, SOMETHING WE

1208
00:41:53,688 --> 00:41:54,455
WOULDN'T HAVE THOUGHT ABOUT

1209
00:41:54,455 --> 00:41:55,556
WITHOUT THESE RESULTS.

1210
00:41:55,556 --> 00:41:59,760
SO GENES INVOLVED IN ACTIVE

1211
00:41:59,760 --> 00:42:01,362
CYTOSKELETON ARE DOWN AS WELL AS

1212
00:42:01,362 --> 00:42:01,929
SOME LIPID COMPONENTS.

1213
00:42:01,929 --> 00:42:03,297
THIS ACTUALLY TIES INTO WHAT'S

1214
00:42:03,297 --> 00:42:05,900
KNOWN FROM THE TUMOR FIELD, SO

1215
00:42:05,900 --> 00:42:07,201
THE CYTOTOXIC T-CELL NEEDS TO

1216
00:42:07,201 --> 00:42:08,469
APPLY FORCE TO ITS TARGET CELL,

1217
00:42:08,469 --> 00:42:11,939
IT NEEDS TO STRETCH TO BE ABLE

1218
00:42:11,939 --> 00:42:13,374
TO INSERT INTO THE MEMBRANE.

1219
00:42:13,374 --> 00:42:16,577
ACTUALLY THE SQUISHIER THAT CELL

1220
00:42:16,577 --> 00:42:18,212
IS, THE LESS THAT CTL IS ABLE TO

1221
00:42:18,212 --> 00:42:21,048
KILL IT AND THIS IS AN ACTUALLY

1222
00:42:21,048 --> 00:42:22,817
PRETTY REMARKABLE EFFECT.

1223
00:42:22,817 --> 00:42:24,485
SO ARE SURVIVORS BIOPHYSICALLY

1224
00:42:24,485 --> 00:42:25,553
DIFFERENT FROM THE CELLS THAT

1225
00:42:25,553 --> 00:42:27,588
WERE BYSTANDERS?  THE MOVIE IS

1226
00:42:27,588 --> 00:42:29,423
NOT GOING TO WORK UNFORTUNATELY

1227
00:42:29,423 --> 00:42:31,058
BUT WE USE A METHOD WHERE YOU

1228
00:42:31,058 --> 00:42:32,827
FORM A TETHER WITH TARGET CELLS

1229
00:42:32,827 --> 00:42:34,161
AND YOU PULL THE BEAD AWAY AND

1230
00:42:34,161 --> 00:42:35,029
YOU MEASURE THE FORCE IT TAKES

1231
00:42:35,029 --> 00:42:36,464
TO PULL THAT TETHER, WHICH TELLS

1232
00:42:36,464 --> 00:42:40,334
YOU ABOUT THE MEMBRANE TENSION.

1233
00:42:40,334 --> 00:42:41,969
LONG STORY SHORT, THESE INFECTED

1234
00:42:41,969 --> 00:42:43,938
CELLS THAT SURVIVE CTL KILL

1235
00:42:43,938 --> 00:42:45,506
HAVING LESS MEMBRANE TENSION

1236
00:42:45,506 --> 00:42:47,508
THAN THE BYSTANDERS THAT WERE IN

1237
00:42:47,508 --> 00:42:48,976
THE SAME WELL, SO WE ARE

1238
00:42:48,976 --> 00:42:51,512
SELECTING FOR CELLS THAT ARE,

1239
00:42:51,512 --> 00:42:53,280
FOR LACK OF A BETTER WORD,

1240
00:42:53,280 --> 00:42:56,250
SQUISHIER AND HARDER TO KILL.

1241
00:42:56,250 --> 00:42:57,451
IS THERE ANYTHING WE CAN DO

1242
00:42:57,451 --> 00:42:57,985
ABOUT THIS?

1243
00:42:57,985 --> 00:42:59,453
AGAIN THE CANCER FIELD HAS SOME

1244
00:42:59,453 --> 00:43:00,421
ANSWERS WE CAN LOOK TO.

1245
00:43:00,421 --> 00:43:03,591
THERE ARE WAYS TO STIFFEN CELL

1246
00:43:03,591 --> 00:43:05,226
MEMBRANES, BOTH IN VITRO AND IN

1247
00:43:05,226 --> 00:43:07,661
VIVO, IN PARTICULAR BY DEPLETING

1248
00:43:07,661 --> 00:43:08,996
CHOLESTEROL, SO CAN WE ENHANCE

1249
00:43:08,996 --> 00:43:10,531
KILLING OF HIV INFECTED CELLS

1250
00:43:10,531 --> 00:43:11,332
USING THIS APPROACH?

1251
00:43:11,332 --> 00:43:12,299
THAT'S SOMETHING WE WANT TO DO

1252
00:43:12,299 --> 00:43:12,733
NEXT.

1253
00:43:12,733 --> 00:43:13,768
THE OTHER MECHANISM THAT CAME

1254
00:43:13,768 --> 00:43:17,138
OUT IS WHAT WE CALL AVIDITY

1255
00:43:17,138 --> 00:43:18,572
ESCAPE.

1256
00:43:18,572 --> 00:43:21,542
MEANING A CTL HAS TO NOT ONLY

1257
00:43:21,542 --> 00:43:24,044
BIND TCR AND MHC1, THERE'S

1258
00:43:24,044 --> 00:43:25,379
ADHESION MOLECULES THAT NEED TO

1259
00:43:25,379 --> 00:43:30,317
INTERACT SO THE TARGET CELL HAS

1260
00:43:30,317 --> 00:43:34,355
ICAM-1.

1261
00:43:34,355 --> 00:43:36,123
ICAM-1 WAS DOWN ON SURVIVORS SO

1262
00:43:36,123 --> 00:43:38,325
HARDER FOR CTL TO GRAB ON TO

1263
00:43:38,325 --> 00:43:39,527
THESE TARGET CELLS AND WE

1264
00:43:39,527 --> 00:43:42,496
CONFIRM THIS BY FLOW CYTOMETRY,

1265
00:43:42,496 --> 00:43:44,698
THERE'S LESS ICAM-1 ON

1266
00:43:44,698 --> 00:43:45,032
SURVIVORS.

1267
00:43:45,032 --> 00:43:46,567
THEY'RE HARDER FOR THE CTL TO

1268
00:43:46,567 --> 00:43:47,668
GRAB ON TO.

1269
00:43:47,668 --> 00:43:49,103
AGAIN IN PARALLEL WITH RECENT

1270
00:43:49,103 --> 00:43:53,507
FINDING IN CANCER, ONE MECHANISM

1271
00:43:53,507 --> 00:43:57,111
OF IMMUNE EVASION IS THEY DON'T

1272
00:43:57,111 --> 00:43:59,447
UPREGULATE ICAM-1, THE CTL

1273
00:43:59,447 --> 00:44:00,414
CANNOT GRAB ON TO THESE CELLS.

1274
00:44:00,414 --> 00:44:01,515
IS THERE ANYTHING WE CAN DO

1275
00:44:01,515 --> 00:44:02,616
ABOUT IT?

1276
00:44:02,616 --> 00:44:03,717
THERE ARE SMALL MOLECULES UNDER

1277
00:44:03,717 --> 00:44:06,020
DEVELOPMENT TO ENHANCE

1278
00:44:06,020 --> 00:44:07,354
LFA1 ACTIVATION OR ICAM

1279
00:44:07,354 --> 00:44:09,757
EXPRESSION, SO MAYBE WE CAN MAKE

1280
00:44:09,757 --> 00:44:11,325
THESE CELLS STICKIER.

1281
00:44:11,325 --> 00:44:13,394
AND THERE'S EFFORTS TO ENGINEER

1282
00:44:13,394 --> 00:44:15,696
T-CELLS IN CARS WITH HIGHER

1283
00:44:15,696 --> 00:44:17,698
AVIDITY VERSIONINGS OF LFA1 THAT

1284
00:44:17,698 --> 00:44:18,899
CAN BIND TO JUST THE SMALL

1285
00:44:18,899 --> 00:44:21,001
AMOUNTS OF ICAM1 THAT MIGHT BE

1286
00:44:21,001 --> 00:44:22,736
LEFT ON THESE SURVIVORS, SO

1287
00:44:22,736 --> 00:44:23,938
THESE ARE TWO NEW APPROACHES.

1288
00:44:23,938 --> 00:44:27,141
THIS IS MORE JUST AN

1289
00:44:27,141 --> 00:44:28,909
ADVERTISEMENT FOR THE POSTER.

1290
00:44:28,909 --> 00:44:30,644
PLEASE SEE HIM AS WELL, BUT THE

1291
00:44:30,644 --> 00:44:31,412
OTHER THING WE SAW IS THAT

1292
00:44:31,412 --> 00:44:33,848
THERE'S A CLEAR METABOLIC

1293
00:44:33,848 --> 00:44:34,849
SIGNATURES OF CELLS THAT SURVIVE

1294
00:44:34,849 --> 00:44:35,282
KILLING.

1295
00:44:35,282 --> 00:44:37,151
THERE'S LESS METABOLICALLY

1296
00:44:37,151 --> 00:44:37,485
ACTIVE.

1297
00:44:37,485 --> 00:44:38,652
WE THINK THIS IS LINKED TO THE

1298
00:44:38,652 --> 00:44:41,121
FACT THAT REACTIVE OXYGEN

1299
00:44:41,121 --> 00:44:42,223
SPECIES ARE AN IMPORTANT

1300
00:44:42,223 --> 00:44:45,860
EXECUTER OF CTL KILLING AND

1301
00:44:45,860 --> 00:44:49,797
CT LS TARGET A CELL, THOSE

1302
00:44:49,797 --> 00:44:51,232
REACTIVE OXYGEN SPECIES WREAK

1303
00:44:51,232 --> 00:44:52,766
HAVOC.

1304
00:44:52,766 --> 00:44:54,535
SO IF A CELL IS NOT

1305
00:44:54,535 --> 00:44:55,736
METABOLICALLY ACTIVE AND DOESN'T

1306
00:44:55,736 --> 00:44:57,371
HAVE ENOUGH REACTIVE OXYGEN

1307
00:44:57,371 --> 00:44:59,473
SPECIES, IT'S GOING TO BE LESS

1308
00:44:59,473 --> 00:45:00,341
SUSCEPTIBLE TO KILLING.

1309
00:45:00,341 --> 00:45:02,443
PLEASE DO SEE ALBERTO'S POSTER

1310
00:45:02,443 --> 00:45:04,345
BECAUSE THERE'S A SAFE AND WELL

1311
00:45:04,345 --> 00:45:05,179
TOLERATED DRUG WHICH INCREASES

1312
00:45:05,179 --> 00:45:07,147
LEVELS OF REACTIVE OXYGEN

1313
00:45:07,147 --> 00:45:08,716
SPECIES, AND HE SHOWS THAT THIS

1314
00:45:08,716 --> 00:45:10,584
SENSITIZES THESE CELLS TO BEING

1315
00:45:10,584 --> 00:45:12,987
KILLED BY CYTOTOXIC T-CELLS.

1316
00:45:12,987 --> 00:45:14,488
SO CONCLUSIONS, HIV INFECTED

1317
00:45:14,488 --> 00:45:17,625
CELLS DO VARY IN THEIR

1318
00:45:17,625 --> 00:45:19,360
SUSCEPTIBILITY TO KILLING, WE

1319
00:45:19,360 --> 00:45:21,028
WANT TO OF COURSE

1320
00:45:21,028 --> 00:45:22,229
CROSS-REFERENCE THIS WITH THE

1321
00:45:22,229 --> 00:45:23,230
CHARACTERIZATION OF RESERVOIR

1322
00:45:23,230 --> 00:45:24,665
HARBORING CELLS SO WE'RE DOING

1323
00:45:24,665 --> 00:45:26,734
THAT IN THE COLLABORATORY.

1324
00:45:26,734 --> 00:45:28,402
RESISTANT CELLS HAVE DISTINCTIVE

1325
00:45:28,402 --> 00:45:30,070
PROPERTIES.

1326
00:45:30,070 --> 00:45:32,406
BCL2, BCL2 FAMILY MEMBERS ARE AN

1327
00:45:32,406 --> 00:45:33,407
IMPORTANT MECHANISM BUT THERE'S

1328
00:45:33,407 --> 00:45:35,309
OTHER MECHANISMS AS WELL.

1329
00:45:35,309 --> 00:45:37,177
MANY OTHER MECHANISMS THAT WE'RE

1330
00:45:37,177 --> 00:45:38,913
JUST SIFTING THROUGH NOW AND WE

1331
00:45:38,913 --> 00:45:40,915
HOPE TO OFFER MORE THERAPEUTIC

1332
00:45:40,915 --> 00:45:42,783
TARGETS, MORE WAYS TO ENHANCE

1333
00:45:42,783 --> 00:45:44,752
KILLING TO OUR FRIENDS THAT DO

1334
00:45:44,752 --> 00:45:45,819
TRANSLATIONAL RESEARCH AS WELL

1335
00:45:45,819 --> 00:45:47,288
AS DEVELOPING SOME OF THOSE

1336
00:45:47,288 --> 00:45:48,389
THINGS WITHIN REACH.

1337
00:45:48,389 --> 00:45:52,259
WITH THAT, I'LL WRAP UP.

1338
00:45:52,259 --> 00:45:57,064
[APPLAUSE]

1339
00:45:57,064 --> 00:45:57,831
>> SORRY.

1340
00:45:57,831 --> 00:45:59,233
THESE ARE MY ACKNOWLEDGMENTS.

1341
00:45:59,233 --> 00:46:00,568
>> SO I'M GOING TO PRESENT
VERY

1342
00:46:00,568 --> 00:46:03,637
QUICKLY THE COMMUNITY PROGRAM

1343
00:46:03,637 --> 00:46:05,005
OVERVIEW JUST TO SAY THAT WE DO

1344
00:46:05,005 --> 00:46:06,307
HAVE SOME SPECIFIC AIMS, MAINLY

1345
00:46:06,307 --> 00:46:08,042
WHAT WE'RE TRYING TO DO IS BUILD

1346
00:46:08,042 --> 00:46:14,114
THE CAPACITY AND LIT ARE SEE OFO

1347
00:46:14,114 --> 00:46:19,620
ENGAGE MEAN AMINOING MEANINGFULE

1348
00:46:19,620 --> 00:46:19,954
CONVERSATION.

1349
00:46:19,954 --> 00:46:21,322
WE HAVE A REACH COMMUNITY

1350
00:46:21,322 --> 00:46:21,755
ADVISORY BOARD.

1351
00:46:21,755 --> 00:46:23,891
IT WAS ACTUALLY ESTABLISHED LAST

1352
00:46:23,891 --> 00:46:24,325
YEAR.

1353
00:46:24,325 --> 00:46:26,660
WE ORIGINALLY HAD AN ADVISORY

1354
00:46:26,660 --> 00:46:28,462
BOARD THAT WAS CONNECTED WITH

1355
00:46:28,462 --> 00:46:30,598
WEILL CORNELL MEDICINE THAT WAS

1356
00:46:30,598 --> 00:46:31,365
HIV-FOCUSED, BOTH IN THEIR

1357
00:46:31,365 --> 00:46:32,232
PREVENTION AND TREATMENT

1358
00:46:32,232 --> 00:46:33,233
PROGRAM, BUT DECIDED REACH

1359
00:46:33,233 --> 00:46:34,568
SHOULD HAVE ITS OWN.

1360
00:46:34,568 --> 00:46:36,103
SO BRANCHED OFF AND SO THESE ARE

1361
00:46:36,103 --> 00:46:39,373
SOME OF THEIR INITIAL MILEST 

1362
00:46:39,373 --> 00:46:40,274
MILESTONES.

1363
00:46:40,274 --> 00:46:41,675
WE'VE HAD A NUMBER OF COMMUNITY

1364
00:46:41,675 --> 00:46:43,043
EVENTS AND WE'VE REALLY TRIED TO

1365
00:46:43,043 --> 00:46:45,679
ENGAGE A WIDE VARIETY OF

1366
00:46:45,679 --> 00:46:46,880
COMMUNITY IN THE NEW YORK CITY

1367
00:46:46,880 --> 00:46:47,314
AREA.

1368
00:46:47,314 --> 00:46:48,582
I'VE FOCUSED HERE ON JUST A FEW

1369
00:46:48,582 --> 00:46:49,750
BUT IN PARTICULAR, I THINK ONE

1370
00:46:49,750 --> 00:46:51,418
OF OUR MOST UNIQUE IS THAT WE

1371
00:46:51,418 --> 00:46:54,054
SPONSORED A RAVE, A BALL, TO

1372
00:46:54,054 --> 00:46:55,656
REACH THE BALLROOM COMMUNITY IN

1373
00:46:55,656 --> 00:46:56,457
NEW YORK CITY.

1374
00:46:56,457 --> 00:47:03,897
WE'VE ALSO GONE TO DIFFERENT

1375
00:47:03,897 --> 00:47:05,532
BURROUGHS, WE PARTNERED WITH THE

1376
00:47:05,532 --> 00:47:08,102
NEW YORK CITY LGBTQ CENTER SO A

1377
00:47:08,102 --> 00:47:08,769
VARIETY OF EVENTS THERE.

1378
00:47:08,769 --> 00:47:10,971
WE DO HAVE A FOCUS ON UGANDA.

1379
00:47:10,971 --> 00:47:14,375
SOME OF YOU HAVE SEEN

1380
00:47:14,375 --> 00:47:15,776
JOSEPHINE'S SERIES OF JOJO, WE

1381
00:47:15,776 --> 00:47:16,977
WERE ABLE TO SPONSOR THAT

1382
00:47:16,977 --> 00:47:18,679
THROUGH REACH, FIRST AS PART OF

1383
00:47:18,679 --> 00:47:22,816
THE ADD VO ADVOCACY COMMUNITY AN

1384
00:47:22,816 --> 00:47:25,419
CONTINUING ON THROUGH OUR

1385
00:47:25,419 --> 00:47:27,154
CUREROAR PROGRAM.

1386
00:47:27,154 --> 00:47:28,255
IN ADDITION HIGHLIGHTING ANOTHER

1387
00:47:28,255 --> 00:47:29,256
INDIVIDUAL WHO WAS SUPPOSED TO

1388
00:47:29,256 --> 00:47:30,924
BE HERE BUT UNFORTUNATELY

1389
00:47:30,924 --> 00:47:32,793
COULDN'T GET THEIR VISA TO COME,

1390
00:47:32,793 --> 00:47:33,861
BUT CHARLES BROWN AS WELL.

1391
00:47:33,861 --> 00:47:34,995
JUST TO HIGHLIGHT, ONE OF THE

1392
00:47:34,995 --> 00:47:37,498
THINGS THAT WE REALLY STRIVE FOR

1393
00:47:37,498 --> 00:47:38,699
IS TO INVEST INTO THE COMMUNITY

1394
00:47:38,699 --> 00:47:40,701
SO THEY CAN AGAIN MEANINGFULLY

1395
00:47:40,701 --> 00:47:41,568
ENGAGE AND PART OF THE ONE OF

1396
00:47:41,568 --> 00:47:42,469
THE METRICS WE WORK ON IS

1397
00:47:42,469 --> 00:47:43,570
THINKING ABOUT HOW OFTEN DO

1398
00:47:43,570 --> 00:47:44,772
PEOPLE ASK QUESTIONS AND WHAT

1399
00:47:44,772 --> 00:47:45,739
ARE THE QUALITY OF QUESTIONS

1400
00:47:45,739 --> 00:47:48,342
THAT THEY'RE ASKING AND SO

1401
00:47:48,342 --> 00:47:50,944
THINKING ABOUT CHARLES COMING IN

1402
00:47:50,944 --> 00:47:54,982
ALMOST TWO YEARS AGO ASKING WHAT

1403
00:47:54,982 --> 00:47:56,850
IS A VIRAL RESERVOIR TO NOW ON

1404
00:47:56,850 --> 00:47:58,419
THE ZOOM THAT WE HAD, THE RAVE

1405
00:47:58,419 --> 00:48:00,154
WE HAD OCTOBER 11TH JUST TWO

1406
00:48:00,154 --> 00:48:02,690
DAYS AGO FOR OUR COMMUNITY,

1407
00:48:02,690 --> 00:48:05,259
ASKING DR. JANET SILICANO ABOUT

1408
00:48:05,259 --> 00:48:07,695
THE DIFFERENCES IN VIRAL DANA

1409
00:48:07,695 --> 00:48:12,966
MDYNAMICS, ASKING QUESTIONS THAT

1410
00:48:12,966 --> 00:48:15,102
CAN REALLY TEASE OUT WHAT IS

1411
00:48:15,102 --> 00:48:15,769
MEANINGFUL FOR COMMUNITIES.

1412
00:48:15,769 --> 00:48:16,970
SO THOSE ARE THINGS THAT WE'RE

1413
00:48:16,970 --> 00:48:20,040
TRACKING AS WELL.

1414
00:48:20,040 --> 00:48:21,308
AGAIN VERY QUICKLY, I THINK A

1415
00:48:21,308 --> 00:48:22,576
LOT TO SAY AND WOULD LOVE TO

1416
00:48:22,576 --> 00:48:24,144
CHAT WITH OTHERS AFTER THE FACT

1417
00:48:24,144 --> 00:48:25,212
IF YOU HAVE MORE QUESTIONS, BUT

1418
00:48:25,212 --> 00:48:27,114
WE ARE REALLY THINKING ABOUT

1419
00:48:27,114 --> 00:48:29,183
AGAIN DIVERSIFYING OUR CAB, OUR

1420
00:48:29,183 --> 00:48:30,184
COMMUNITY ADVISORY BOARD IS

1421
00:48:30,184 --> 00:48:33,287
BASED IN NEW YORK CITY, SO WE DO

1422
00:48:33,287 --> 00:48:34,722
AGAIN HAVE THAT EXTENSION OF THE

1423
00:48:34,722 --> 00:48:36,256
UGANDA PROGRAM WHICH WE HAVE TO

1424
00:48:36,256 --> 00:48:37,658
KEEP SEPARATE FOR TIME ZONE

1425
00:48:37,658 --> 00:48:38,625
DIFFERENCES BUT OUR COMMUNITY

1426
00:48:38,625 --> 00:48:39,727
ADVISORY BOARD TO DEEPEN THAT

1427
00:48:39,727 --> 00:48:40,160
OUT.

1428
00:48:40,160 --> 00:48:43,964
WE'RE ALSO PARTNERING WITH THE

1429
00:48:43,964 --> 00:48:45,265
NEW YORK CITY DEPARTMENT OF

1430
00:48:45,265 --> 00:48:48,268
HEALTH FOR A WEBINAR SERIES LOOK

1431
00:48:48,268 --> 00:48:49,770
BEING AT INTRODUCTION, SEX AND

1432
00:48:49,770 --> 00:48:50,804
GENDER AND HOW DOES THE

1433
00:48:50,804 --> 00:49:01,415
ENVIRONMENT ACTUALLY -- JUST

1434
00:49:01,415 --> 00:49:02,649
LIKE YOU LEVERAGE THE SCIENCE,

1435
00:49:02,649 --> 00:49:03,984
WE ARE TRYING TO LEVERAGE OUR

1436
00:49:03,984 --> 00:49:04,985
COMMUNITY AND COLLABORATORY

1437
00:49:04,985 --> 00:49:06,086
PROGRAMS TO REALLY HEIGHTEN THAT

1438
00:49:06,086 --> 00:49:09,256
OUT AND THAT INCLUDES CROSS

1439
00:49:09,256 --> 00:49:10,924
COLLABORATORY LEARNING, IT

1440
00:49:10,924 --> 00:49:12,593
INCLUDES PARTNERING IN

1441
00:49:12,593 --> 00:49:13,594
AMPLIFYING EVENTS IN DIFFERENT

1442
00:49:13,594 --> 00:49:14,461
REGIONS AND PARTS OF THE WORLD

1443
00:49:14,461 --> 00:49:16,330
BUT ALSO REALLY TRYING TO AGAIN

1444
00:49:16,330 --> 00:49:18,799
STRENGTHEN THE KNOWLEDGE SHARING

1445
00:49:18,799 --> 00:49:20,067
AND BEST PRACTICE TO FIGURE OUT

1446
00:49:20,067 --> 00:49:21,301
WHAT WORKS IN NEW YORK CITY, CAN

1447
00:49:21,301 --> 00:49:23,203
IT ALSO WORK IN BOSTON, CAN IT

1448
00:49:23,203 --> 00:49:26,373
WORK IN ZIMBABWE AND E UGANDA, O

1449
00:49:26,373 --> 00:49:28,408
WEE REALLY TRIED TO TAKE THAT ON

1450
00:49:28,408 --> 00:49:29,810
AS PART OF THIS PROGRAM AS WELL.

1451
00:49:29,810 --> 00:49:31,478
I KNOW I'M OUT OF TIME.

1452
00:49:31,478 --> 00:49:34,047
HERE COMES SANDRA TO KICK ME

1453
00:49:34,047 --> 00:49:34,515
OFF.

1454
00:49:34,515 --> 00:49:35,015
SO THANK YOU ALL.

1455
00:49:35,015 --> 00:49:43,357
[APPLAUSE]

1456
00:49:43,357 --> 00:49:46,059
>> SINCE WE'RE A LITTLE
BEHIND

1457
00:49:46,059 --> 00:49:51,064
FINAL WETIME WE'LL SKIP THE QUED

1458
00:49:51,064 --> 00:49:52,132
ANSWER PERIOD AND ASK YOU TO

1459
00:49:52,132 --> 00:49:53,300
PLEASE TALK TO THE MEMBERS OF

1460
00:49:53,300 --> 00:49:54,234
THE REACH COLLABORATORY DURING

1461
00:49:54,234 --> 00:49:55,369
THE COFFEE BREAK.

1462
00:49:55,369 --> 00:49:58,438
SO LET'S MOVE ON TO THE NEXT

1463
00:49:58,438 --> 00:50:08,549
GROUP.

1464
00:50:43,150 --> 00:50:45,853
>> BEFORE WE MOVE ON TO
THE NEXT

1465
00:50:45,853 --> 00:50:46,620
COLLABORATORY, WE WANT TO LET

1466
00:50:46,620 --> 00:50:48,822
YOU KNOW THERE IS AN OVERFLOW

1467
00:50:48,822 --> 00:50:50,257
ROOM ACROSS THIS AUDITORIUM AND

1468
00:50:50,257 --> 00:50:52,125
ALSO FOR THE PEOPLE WATCHING

1469
00:50:52,125 --> 00:50:53,293
ONLINE, THERE IS SEND FEEDBACK

1470
00:50:53,293 --> 00:50:54,962
IF YOU HAVE QUESTIONS, THAT'S

1471
00:50:54,962 --> 00:50:55,796
ONE WAY TO SEND US THE

1472
00:50:55,796 --> 00:50:56,063
QUESTIONS.

1473
00:50:56,063 --> 00:50:58,999
THANK YOU.

1474
00:50:58,999 --> 00:50:59,633
>> THANK YOU.

1475
00:50:59,633 --> 00:51:00,868
GOOD MORNING, EVERYONE.

1476
00:51:00,868 --> 00:51:02,035
MY NAME IS TANIA LOMBO.

1477
00:51:02,035 --> 00:51:05,706
I'M A PROGRAM OFFICER IN THE

1478
00:51:05,706 --> 00:51:07,407
PREVENTION SCIENCE PROGRAM OF

1479
00:51:07,407 --> 00:51:10,744
THE DIVISION OF AIDS AT NIAID.

1480
00:51:10,744 --> 00:51:12,346
THIS MORNING I HAVE THE PLEASURE

1481
00:51:12,346 --> 00:51:14,114
TO INTRODUCE THE PEDIATRIC

1482
00:51:14,114 --> 00:51:16,183
ADOLESCENT VIRUS ELIMINATION

1483
00:51:16,183 --> 00:51:18,785
COLLABORATORY, OR PAVE.

1484
00:51:18,785 --> 00:51:21,488
THIS COLLABORATORY IS BASED IN

1485
00:51:21,488 --> 00:51:22,155
THE JOHNS HOPKINS UNIVERSITY AND

1486
00:51:22,155 --> 00:51:28,829
IS LTODAY YOU WILL HEAR PROGRESD

1487
00:51:28,829 --> 00:51:30,931
UPDATES FROM ALL THE RESEARCH

1488
00:51:30,931 --> 00:51:33,000
FOCI INCLUDING THE FOURTH

1489
00:51:33,000 --> 00:51:35,736
RESEARCH FOCUS THAT IS CLOSER

1490
00:51:35,736 --> 00:51:36,637
FOR THIS COLLABORATORY.

1491
00:51:36,637 --> 00:51:38,505
WE WANT TO EMPHASIZE THAT THIS

1492
00:51:38,505 --> 00:51:40,807
IS THE ONLY COLLABORATORY

1493
00:51:40,807 --> 00:51:43,677
FOCUSED ON HIV CURE RESEARCH IN

1494
00:51:43,677 --> 00:51:45,012
PEDIATRIC POPULATIONS.

1495
00:51:45,012 --> 00:51:47,080
WITH THAT, I WILL HAND IT OVER

1496
00:51:47,080 --> 00:51:53,587
TO YOU, DEBBIE.

1497
00:51:53,587 --> 00:51:54,421
>> GOOD MORNING.

1498
00:51:54,421 --> 00:51:56,990
THANK YOU, TANIA.

1499
00:51:56,990 --> 00:51:58,191
I'M GOING TO GET STARTED.

1500
00:51:58,191 --> 00:52:02,229
DO WE GET 5 MINUTES BACK?

1501
00:52:02,229 --> 00:52:04,264
SO AS TANIA SAID, THIS

1502
00:52:04,264 --> 00:52:06,233
COLLABORATORY IS THE FIRST

1503
00:52:06,233 --> 00:52:08,402
PEDIATRIC CURE COLLABORATORY AND

1504
00:52:08,402 --> 00:52:09,670
WE'RE REALLY, REALLY DELIGHTED

1505
00:52:09,670 --> 00:52:11,305
TO JOIN THE GROUP HERE.

1506
00:52:11,305 --> 00:52:15,442
SO I CO-LEAD WITH THIS ANN

1507
00:52:15,442 --> 00:52:16,209
CHAHROUDI.

1508
00:52:16,209 --> 00:52:17,344
SO TODAY WE'RE GOING TO PROVIDE

1509
00:52:17,344 --> 00:52:18,779
A HIGH LEVEL VIEW WITH SOME

1510
00:52:18,779 --> 00:52:19,980
HIGHLIGHTS IN TERMS OF THE

1511
00:52:19,980 --> 00:52:21,515
DIRECTION OF THE COLLABORATORY

1512
00:52:21,515 --> 00:52:23,483
AND SOME KEY FINDINGS TO DATE.

1513
00:52:23,483 --> 00:52:25,052
REALLY IN ORDER TO BE ABLE TO

1514
00:52:25,052 --> 00:52:26,153
SYNERGIZE OUR ACTIVITIES WITH

1515
00:52:26,153 --> 00:52:28,121
THE EXISTING ADULT

1516
00:52:28,121 --> 00:52:28,488
COLLABORATORIES.

1517
00:52:28,488 --> 00:52:29,990
AND SO I'LL GIVE AN OVERVIEW AND

1518
00:52:29,990 --> 00:52:32,893
ALSO AN UPDATE ON THE RESEARCH

1519
00:52:32,893 --> 00:52:34,094
FOCUS AREA ONE ON THE

1520
00:52:34,094 --> 00:52:35,963
PATHOGENESIS OF RESERVOIRS IN

1521
00:52:35,963 --> 00:52:37,664
CHILDREN, AND THEN ALSO THE

1522
00:52:37,664 --> 00:52:40,500
HUMAN DATA IN RF2 IN TERMS OF

1523
00:52:40,500 --> 00:52:42,135
CONTROL AND WHAT WE'VE LEARNED

1524
00:52:42,135 --> 00:52:43,603
OF CONTROL IN HIV CHILDREN

1525
00:52:43,603 --> 00:52:45,339
LIVING WITH PERINATAL HIV AND

1526
00:52:45,339 --> 00:52:50,944
THEN TURN IT OVER TO MAURICIO

1527
00:52:50,944 --> 00:52:53,547
MARTINS.

1528
00:52:53,547 --> 00:52:56,316
STUDYING -- TO END UP WITH A

1529
00:52:56,316 --> 00:53:00,387
SINGLE SHOT IN THE ARM FOR VIRUS

1530
00:53:00,387 --> 00:53:01,788
REPLICATION, FOLLOWED BY ANN

1531
00:53:01,788 --> 00:53:03,523
CHAHROUDI AND HER PIONEERING

1532
00:53:03,523 --> 00:53:05,258
WORK ON SURGE AND PURGE AND

1533
00:53:05,258 --> 00:53:07,327
VIROLOGIC CONTROL WITH DIFFERENT

1534
00:53:07,327 --> 00:53:08,528
MONOCLONAL ANTIBODIES.

1535
00:53:08,528 --> 00:53:10,797
AND THEN COME BACK TO A NEW

1536
00:53:10,797 --> 00:53:12,132
RESEARCH FOCUS AREA THAT'S

1537
00:53:12,132 --> 00:53:13,967
SPECIFIC TO THE PEDIATRIC

1538
00:53:13,967 --> 00:53:15,736
COLLABORATORY, RF 4, WHICH IS

1539
00:53:15,736 --> 00:53:19,606
REALLY DEVELOPING LABORATORY

1540
00:53:19,606 --> 00:53:21,441
ASSAYS TO PROBE GIVEN THE SMALL

1541
00:53:21,441 --> 00:53:22,442
BLOOD VOLUMES THAT ARE

1542
00:53:22,442 --> 00:53:23,577
OBTAINABLE.

1543
00:53:23,577 --> 00:53:26,880
THIS RF 4 IS CO-LED BY MYSELF

1544
00:53:26,880 --> 00:53:30,050
AND SUMITA AND OF COURSE OUR

1545
00:53:30,050 --> 00:53:31,418
COMMUNITY PARTNERSHIP WITH AVAC.

1546
00:53:31,418 --> 00:53:33,186
SO I WANTED TO START WITH OUR

1547
00:53:33,186 --> 00:53:36,023
MISSION TO THINK ABOUT WHAT

1548
00:53:36,023 --> 00:53:37,391
WE'RE TRYING TO DO, REALLY

1549
00:53:37,391 --> 00:53:38,358
CUTTING EDGE SCIENCE TO

1550
00:53:38,358 --> 00:53:39,793
ESTABLISH A DEEP AND BROAD

1551
00:53:39,793 --> 00:53:41,094
UNDERSTANDING OF THE

1552
00:53:41,094 --> 00:53:42,262
IMMUNOPATHOGENESIS OF PEDIATRIC

1553
00:53:42,262 --> 00:53:44,331
HIV RESERVOIRS.

1554
00:53:44,331 --> 00:53:45,599
AND A KEY COMPONENT ACROSS THE

1555
00:53:45,599 --> 00:53:48,135
AIDS SPECTRUM.

1556
00:53:48,135 --> 00:53:50,137
WE STUDY PERSISTENCE FROM THE

1557
00:53:50,137 --> 00:53:51,505
NEWBORN PERIOD THROUGH AGE 24 IN

1558
00:53:51,505 --> 00:53:53,040
THOSE LIVING WITH PERINATAL HIV

1559
00:53:53,040 --> 00:53:54,775
AND REALLY TO DEMONSTRATE SAFETY

1560
00:53:54,775 --> 00:53:56,376
AND EFFICACY IN THE NON-HUMAN

1561
00:53:56,376 --> 00:54:02,482
PRIMATE MODELS ON NOVEL AGENTS

1562
00:54:02,482 --> 00:54:04,985
TO PAVE THE WAY FOR

1563
00:54:04,985 --> 00:54:06,953
INTERVENTIONAL STUDIES SO WE

1564
00:54:06,953 --> 00:54:08,155
HOPE TO MOVE THESE CLINICAL

1565
00:54:08,155 --> 00:54:09,089
FINDINGS INTO CLINICAL TRIALS.

1566
00:54:09,089 --> 00:54:10,290
WITH THE VISION REALLY TO

1567
00:54:10,290 --> 00:54:11,825
ACHIEVE SUSTAINED ART-FREE

1568
00:54:11,825 --> 00:54:13,460
CONTROL OF HIV REPLICATION IN

1569
00:54:13,460 --> 00:54:16,029
PEDIATRIC POPULATIONS, THAT THIS

1570
00:54:16,029 --> 00:54:17,230
WILL BE POSSIBLE, WE BELIEVE,

1571
00:54:17,230 --> 00:54:18,899
WITH IMMUNE TARGETED APPROACHES.

1572
00:54:18,899 --> 00:54:20,700
I WANT TO START BY SAYING WE'RE

1573
00:54:20,700 --> 00:54:21,668
A LARGE COLLABORATORY AND WHAT

1574
00:54:21,668 --> 00:54:24,071
THIS FUNDING HAS DONE HAS REALLY

1575
00:54:24,071 --> 00:54:25,205
BROUGHT THE PEDIATRIC SPACE

1576
00:54:25,205 --> 00:54:25,672
TOGETHER.

1577
00:54:25,672 --> 00:54:26,573
THERE ARE MANY INDIVIDUALS WHO

1578
00:54:26,573 --> 00:54:28,842
HAVE BEEN WORKING IN ISOLATION

1579
00:54:28,842 --> 00:54:32,245
AND PEDIATRIC RESERVOIR

1580
00:54:32,245 --> 00:54:33,580
IMMUNOLOGIC BASIS OF PERSISTENCE

1581
00:54:33,580 --> 00:54:35,582
IN CHILDREN, SO WE'RE

1582
00:54:35,582 --> 00:54:37,217
44 INVESTIGATORS AND 18

1583
00:54:37,217 --> 00:54:38,552
INSTITUTIONS IN THE U.S., EUROPE

1584
00:54:38,552 --> 00:54:39,252
AND SOUTH AFRICA.

1585
00:54:39,252 --> 00:54:41,455
AND I WANT TO SAY AS PART OF THE

1586
00:54:41,455 --> 00:54:42,622
REQUIREMENT AS ALL OF YOU KNOW,

1587
00:54:42,622 --> 00:54:43,757
IT WAS A REQUIREMENT FOR

1588
00:54:43,757 --> 00:54:45,125
INDUSTRY PARTNERS, AND WE COULD

1589
00:54:45,125 --> 00:54:46,660
NOT HAVE DONE THIS WITHOUT THE

1590
00:54:46,660 --> 00:54:48,829
INVESTMENT OF OUR INDUSTRY

1591
00:54:48,829 --> 00:54:51,364
PARTNERS AND THEIR PIONEERING

1592
00:54:51,364 --> 00:54:55,035
WORK IN IPD ASSAY AND AS GUIN

1593
00:54:55,035 --> 00:54:56,436
LEE DISCUSSED, REALLY THE

1594
00:54:56,436 --> 00:54:59,272
CHALLENGES IN NON-SUBTYPE B IN

1595
00:54:59,272 --> 00:55:01,641
DEVELOPING THIS ASSAY.

1596
00:55:01,641 --> 00:55:05,145
IMMUNITYBIO, JEFF SAFRIT, AND

1597
00:55:05,145 --> 00:55:07,814
THEN A REALLY NOVEL

1598
00:55:07,814 --> 00:55:11,017
COLLABORATION IS WITH INIMMUNE,

1599
00:55:11,017 --> 00:55:12,219
A CANCER THERAPEUTIC PROGRAM

1600
00:55:12,219 --> 00:55:15,222
THAT ACTUALLY DEVELOPS PRODUCTS

1601
00:55:15,222 --> 00:55:16,523
FOR IMMUNOTHERAPY FOR CANCER,

1602
00:55:16,523 --> 00:55:20,460
AND SO WE BELIEVE INNATE IMMUNE

1603
00:55:20,460 --> 00:55:22,062
ENHANCERS SUCH AS THESE TLR

1604
00:55:22,062 --> 00:55:23,163
AGONISTS ARE GOING TO BE

1605
00:55:23,163 --> 00:55:26,333
CRITICAL FOR HIV SURGE AND PURGE

1606
00:55:26,333 --> 00:55:28,935
STRATEGIES AND THEN THE SMACK

1607
00:55:28,935 --> 00:55:29,903
MIMETICS THAT'S BEING STUDIED IN

1608
00:55:29,903 --> 00:55:31,638
THE ADULT SYSTEMS.

1609
00:55:31,638 --> 00:55:32,739
OUR SCIENTIFIC ADVISORY BOARD

1610
00:55:32,739 --> 00:55:34,374
HAVE BEEN REALLY TREMENDOUS IN

1611
00:55:34,374 --> 00:55:35,308
GUIDING AND SHAPING WITH

1612
00:55:35,308 --> 00:55:36,510
TERRIFIC FEEDBACK IN HOW WE CAN

1613
00:55:36,510 --> 00:55:39,546
DO BETTER IN WHAT WE DO.

1614
00:55:39,546 --> 00:55:40,947
A MAJOR COMPONENT OF OUR

1615
00:55:40,947 --> 00:55:42,382
COMMUNITY ENGAGEMENT IS ACTUALLY

1616
00:55:42,382 --> 00:55:44,451
OUR PARTNERSHIP WITH

1617
00:55:44,451 --> 00:55:46,586
STAKEHOLDERS, WITH GLOBAL -- A

1618
00:55:46,586 --> 00:55:48,255
GLOBAL FOOTPRINT SUCH AS

1619
00:55:48,255 --> 00:55:49,589
ELIZABETH GLAI SER PEDIATRIC

1620
00:55:49,589 --> 00:55:53,026
AIDS FOUNDATION, THE IMPACT

1621
00:55:53,026 --> 00:55:57,063
NETWORK, AVAC, FHI360.

1622
00:55:57,063 --> 00:56:00,300
SO I WANT TO FOCUS YOU TO A MAIN

1623
00:56:00,300 --> 00:56:02,736
PART OF THE PAVE MARTIN DELANEY

1624
00:56:02,736 --> 00:56:06,540
COLLABORATORIES RELIES ON --

1625
00:56:06,540 --> 00:56:09,543
ACCESS CLINICAL TRIAL COHORTS AS

1626
00:56:09,543 --> 00:56:11,545
MARINA DESCRIBED, WE BELIEVE

1627
00:56:11,545 --> 00:56:14,614
THAT TAKING ADVANTAGE OF THESE

1628
00:56:14,614 --> 00:56:16,349
BIOBANKS AND WELL KERIK TIRRIZED

1629
00:56:16,349 --> 00:56:17,450
COHORTS SHOULD BE YOUR STARTING

1630
00:56:17,450 --> 00:56:18,718
POINT FOR UNDERSTANDING BASIC

1631
00:56:18,718 --> 00:56:19,586
MECHANISMS OF PERSISTENCE.

1632
00:56:19,586 --> 00:56:21,555
SO WHAT YOU SEE ON THIS SLIDE AT

1633
00:56:21,555 --> 00:56:25,125
THE FAR LEFT, PARTNERSHIP WITH

1634
00:56:25,125 --> 00:56:27,794
THE IMPAACT NETWORK, THE 12

1635
00:56:27,794 --> 00:56:31,331
COUNTRIES WHERE WE'RE LOCATED,

1636
00:56:31,331 --> 00:56:37,504
HIV SUBTYPES, MOLECULAR TESTING,

1637
00:56:37,504 --> 00:56:39,606
KWAZULU-NATAL WILL PREVENT ON

1638
00:56:39,606 --> 00:56:41,341
THE COHORT AND EARLY INFANT

1639
00:56:41,341 --> 00:56:42,642
TREATMENT STUDY.

1640
00:56:42,642 --> 00:56:45,178
THE EPIICAL CONSORTIUM HAS BEEN

1641
00:56:45,178 --> 00:56:46,279
KEY BECAUSE THEY HAVE SUPPORTED

1642
00:56:46,279 --> 00:56:47,514
A LOT OF THE COHORT STUDIES

1643
00:56:47,514 --> 00:56:51,518
BEING DISCUSSED TODAY.

1644
00:56:51,518 --> 00:56:59,626
THTHE CHER COHORT STUDY SHOWING

1645
00:56:59,626 --> 00:57:02,095
EARLY TREATMENT IN INFANCY IS

1646
00:57:02,095 --> 00:57:02,729
LIFE-SAVING FOR CHILDREN.

1647
00:57:02,729 --> 00:57:04,698
SO I'M GOING TO NOW SWITCH TO RF

1648
00:57:04,698 --> 00:57:09,803
1 AND PEDIATRIC RESERVOIR LE, IM

1649
00:57:09,803 --> 00:57:10,870
GOING TO GIVE THE UPDATES ON

1650
00:57:10,870 --> 00:57:11,972
THIS.

1651
00:57:11,972 --> 00:57:13,406
AND REALLY THE KEY COMPONENT

1652
00:57:13,406 --> 00:57:15,775
HERE IS TO LOOK AT IN DEPTH

1653
00:57:15,775 --> 00:57:17,744
PROFILING OF HIV RESERVOIRS,

1654
00:57:17,744 --> 00:57:20,680
INCLUDING IN THE CENTRAL NERVOUS

1655
00:57:20,680 --> 00:57:22,716
SYSTEM, AND MECHANISMS --

1656
00:57:22,716 --> 00:57:24,150
UNDERSTANDING MECHANISMS OF

1657
00:57:24,150 --> 00:57:25,885
IMMUNE CONTROL AND SOURCES OF

1658
00:57:25,885 --> 00:57:26,553
REBOUND VIREMIA.

1659
00:57:26,553 --> 00:57:30,457
TO REALLY GAIN INSIGHTS INTO HIV

1660
00:57:30,457 --> 00:57:33,159
PERSISTENCE WITH LONG TERM

1661
00:57:33,159 --> 00:57:35,262
VIROLOGIC SUPPRESSION OF

1662
00:57:35,262 --> 00:57:36,529
PERINATAL INFECTION, RF 1 TEAM.

1663
00:57:36,529 --> 00:57:37,631
SO I'M GOING TO START WITH

1664
00:57:37,631 --> 00:57:40,367
REALLY VERY INTRIGUING FINDINGS

1665
00:57:40,367 --> 00:57:45,472
USING THE FLIP SEQ DEEP PROVIRAL

1666
00:57:45,472 --> 00:57:47,641
LANDSCAPE PROFILING IN LONG TERM

1667
00:57:47,641 --> 00:57:49,409
SUPPRESSED EARLY TREATED YOUNG

1668
00:57:49,409 --> 00:57:49,743
ADULTS.

1669
00:57:49,743 --> 00:57:51,077
SO THESE ARE YOUNG ADULTS WHO

1670
00:57:51,077 --> 00:57:52,946
ARE TREATED FROM INFANCY AND NOW

1671
00:57:52,946 --> 00:57:54,814
ARE ABOUT 20 YEARS OF AGE,

1672
00:57:54,814 --> 00:57:56,283
HAVEN'T BEEN SUPPRESSED FOR LONG

1673
00:57:56,283 --> 00:57:56,483
TIME.

1674
00:57:56,483 --> 00:57:59,085
SO THIS IS THE FIRST STUDY OF

1675
00:57:59,085 --> 00:58:02,789
ACTUALLY DOING LUKE PHORESIS IN

1676
00:58:02,789 --> 00:58:03,256
PERINATAL INFECTIONS.

1677
00:58:03,256 --> 00:58:06,893
THIS STUDY WAS CONDUCTED BY OUR

1678
00:58:06,893 --> 00:58:09,729
ITALIAN COLLABORATORS.

1679
00:58:09,729 --> 00:58:11,865
THEY ACTUALLY EMBARKED ON A

1680
00:58:11,865 --> 00:58:14,634
STUDY WHERE THEY DID

1681
00:58:14,634 --> 00:58:15,735
LEUKOPHORESIS ON NINE ADULTS

1682
00:58:15,735 --> 00:58:16,269
LIVING WITH HIV.

1683
00:58:16,269 --> 00:58:18,838
WHAT I WANT TO HIGHLIGHT IS THE

1684
00:58:18,838 --> 00:58:20,273
MEDIAN AGE IS 20 YEARS AT TIME

1685
00:58:20,273 --> 00:58:24,711
OF SAMPLING, MEDIAN AGE AT ART

1686
00:58:24,711 --> 00:58:25,679
WAS 4 MONTHS SUPPRESSED FOR 20

1687
00:58:25,679 --> 00:58:25,912
YEARS.

1688
00:58:25,912 --> 00:58:28,214
MOST OF THESE WERE ARE ACTUALLY

1689
00:58:28,214 --> 00:58:28,448
WOMEN.

1690
00:58:28,448 --> 00:58:29,082
NOT MEN.

1691
00:58:29,082 --> 00:58:30,417
AND THAT'S AN INTRIGUING

1692
00:58:30,417 --> 00:58:30,650
FINDING.

1693
00:58:30,650 --> 00:58:34,087
A LOT OF OUR STUDIES IN CHILDREN

1694
00:58:34,087 --> 00:58:35,689
IN COHORT STUDIES, THOSE

1695
00:58:35,689 --> 00:58:38,058
ENROLLED ARE MOSTLY WOMEN AND

1696
00:58:38,058 --> 00:58:38,391
GIRLS.

1697
00:58:38,391 --> 00:58:42,329
SO THE KEY FINDING HERE USING

1698
00:58:42,329 --> 00:58:44,464
MATHIAS' APPROACH, WHAT YOU SEE

1699
00:58:44,464 --> 00:58:48,168
IN RED IS THE LOCAL HIV COHORT,

1700
00:58:48,168 --> 00:58:49,602
TOTAL HIV DNA LEVELS ARE

1701
00:58:49,602 --> 00:58:53,440
SUBSTANTIALLY LOWER COMPARED

1702
00:58:53,440 --> 00:58:55,575
WITH LONG TERM TREATED ART

1703
00:58:55,575 --> 00:58:55,909
ADULTS.

1704
00:58:55,909 --> 00:58:57,077
WHAT YOU SEE ON THE RIGHT IS

1705
00:58:57,077 --> 00:58:59,312
ACTUALLY THE PROVIRAL -- INTACT

1706
00:58:59,312 --> 00:59:01,448
PROVIRAL DNA LEVEL IS EVEN LOWER

1707
00:59:01,448 --> 00:59:03,616
IN THESE YOUNG ADULTS.

1708
00:59:03,616 --> 00:59:05,151
CONFIRMING THAT EARLY EFFECTIVE

1709
00:59:05,151 --> 00:59:06,252
THERAPY WITH LONG TERM

1710
00:59:06,252 --> 00:59:07,854
SUPPRESSION WHICH MANY GROUPS

1711
00:59:07,854 --> 00:59:10,123
HAVE SHOWN IN DIFFERENT WAYS BY

1712
00:59:10,123 --> 00:59:13,860
MEASURING TOTAL HIV DNA REALLY

1713
00:59:13,860 --> 00:59:15,662
RENDERS HIV TO PERSIST WITH VERY

1714
00:59:15,662 --> 00:59:18,965
LITTLE RESERVOIRS WITH LONG TERM

1715
00:59:18,965 --> 00:59:20,934
SUPPRESSION.

1716
00:59:20,934 --> 00:59:24,838
WHAT I WANT TO SHOW YOU WITH

1717
00:59:24,838 --> 00:59:26,039
LEUKOPHORESIS, THIS STUDY WAS

1718
00:59:26,039 --> 00:59:28,975
DONE BY BEN BONE IN MATHIAS'

1719
00:59:28,975 --> 00:59:30,510
GROUP, THE NUMBER OF CELLS

1720
00:59:30,510 --> 00:59:32,112
ASSAYED, IN GENERAL WHAT YOU SEE

1721
00:59:32,112 --> 00:59:34,481
IS BY THE OPEN CIRCLES REPRESENT

1722
00:59:34,481 --> 00:59:35,749
TWO INDIVIDUALS IN WHOM INTACT

1723
00:59:35,749 --> 00:59:38,418
PRO VIRUSES WERE NOT IDENTIFIED.

1724
00:59:38,418 --> 00:59:39,919
BUT EVENTUALLY WITH SAMPLING

1725
00:59:39,919 --> 00:59:42,822
ENOUGH CELLS, MATHIAS' GROUP

1726
00:59:42,822 --> 00:59:44,791
COULD DETECT INTACT PROVIRAL

1727
00:59:44,791 --> 00:59:45,825
SEQUENCE IN THESE INDIVIDUALS.

1728
00:59:45,825 --> 00:59:48,128
SO WHAT I SHOW HERE ON THE SIDE

1729
00:59:48,128 --> 00:59:49,095
TO REALLY FOCUS YOUR ATTENTION

1730
00:59:49,095 --> 00:59:50,630
ON IS THE NUMBER OF CELLS THAT

1731
00:59:50,630 --> 00:59:54,801
WERE ANALYZED TO BE ABLE TO

1732
00:59:54,801 --> 00:59:56,002
DETECT INTACT PRO VIRUSES IN

1733
00:59:56,002 --> 00:59:57,637
THIS GROUP, AGAIN CONFIRMING

1734
00:59:57,637 --> 01:00:00,440
THAT EARLY LONG TERM SUPPRESSIVE

1735
01:00:00,440 --> 01:00:04,177
ART LEAVES EXCEEDINGLY LOW

1736
01:00:04,177 --> 01:00:05,044
RESERVOIRS IN CHILDREN AND

1737
01:00:05,044 --> 01:00:05,745
ADULTS.

1738
01:00:05,745 --> 01:00:08,515
SO IT WAS IN TREATING THIS

1739
01:00:08,515 --> 01:00:11,351
HAND-PICKED GROUP, 3 OF THE

1740
01:00:11,351 --> 01:00:14,187
9 PARTICIPANTS HAD HLA ALLELES

1741
01:00:14,187 --> 01:00:15,488
THAT HAVE BEEN REPORTED TO BE

1742
01:00:15,488 --> 01:00:16,689
PROTECTIVE IN ADULTS LIVING WITH

1743
01:00:16,689 --> 01:00:20,293
HIV.

1744
01:00:20,293 --> 01:00:21,895
I'M GOING TO QUICKLY SUMMARIZE

1745
01:00:21,895 --> 01:00:23,229
KEY FINDINGS FROM THE STUDY THAT

1746
01:00:23,229 --> 01:00:24,964
I HOPE I CONVINCE YOU FROM THIS

1747
01:00:24,964 --> 01:00:26,566
PROOF OF CONCEPT STUDY THAT THE

1748
01:00:26,566 --> 01:00:28,535
RESERVOIR IS SMALLER WITH LONG

1749
01:00:28,535 --> 01:00:31,604
TERM EARLY PERINATAL INFECTION

1750
01:00:31,604 --> 01:00:34,107
TO INDIVIDUALS HE WAS NOT ABLE

1751
01:00:34,107 --> 01:00:36,709
TO DETECT INTACT PRO VIRUSES,

1752
01:00:36,709 --> 01:00:39,012
THERE WERE SOME HLA PROTECTIVE

1753
01:00:39,012 --> 01:00:40,079
ALLELES THAT NEEDS TO BE

1754
01:00:40,079 --> 01:00:42,482
EXPLORED IN LARGER COHORTS.

1755
01:00:42,482 --> 01:00:44,551
THE OVERARCHING HYPOTHESIS IS

1756
01:00:44,551 --> 01:00:46,619
THERE'S IMMUNE-MEDIATED

1757
01:00:46,619 --> 01:00:48,888
MECHANISM OF CLEARANCE OF THESE

1758
01:00:48,888 --> 01:00:49,989
RESERVOIRS OVER TIME THAT'S

1759
01:00:49,989 --> 01:00:51,624
CONTRIBUTING TO RESERVOIR

1760
01:00:51,624 --> 01:00:53,927
DEPLETION WHICH WE BELIEVE WILL

1761
01:00:53,927 --> 01:00:55,628
INFORM THERAPEUTIC INTERVENTIONS

1762
01:00:55,628 --> 01:00:57,130
FOR LONG TERM SUPPRESSED

1763
01:00:57,130 --> 01:00:58,198
PERINATAL INFECTIONS.

1764
01:00:58,198 --> 01:00:59,833
THESE STUDIES WERE CARRIED OUT

1765
01:00:59,833 --> 01:01:01,534
BY BEN BONE AS THE MAIN

1766
01:01:01,534 --> 01:01:03,403
INDIVIDUAL IN MATHIAS' LAB.

1767
01:01:03,403 --> 01:01:05,271
SO I'M GOING TO SWITCH GEARS TO

1768
01:01:05,271 --> 01:01:10,710
THE SECOND AIM IN RF 1,

1769
01:01:10,710 --> 01:01:21,721
HARNESSING IMMUNOGENIC IMMUNOGEN

1770
01:01:23,690 --> 01:01:26,192
PURSUIT OF PEDIATRIC HIV

1771
01:01:26,192 --> 01:01:26,526
ERADICATION.

1772
01:01:26,526 --> 01:01:28,828
 -- WENT OFF THERAPY AND HAS NOW

1773
01:01:28,828 --> 01:01:30,163
BEEN A POST TREATMENT CONTROL

1774
01:01:30,163 --> 01:01:31,965
FOR NOW 15 YEARS, WHICH

1775
01:01:31,965 --> 01:01:33,600
IDENTIFIED IN THAT ADOLESCENT

1776
01:01:33,600 --> 01:01:35,568
NOW IS THAT THERE WAS LOW LEVELS

1777
01:01:35,568 --> 01:01:37,737
OF CCR5 EXPRESSION, LOW LEVELS

1778
01:01:37,737 --> 01:01:39,272
OF IMMUNE ACTIVATION AND SOME

1779
01:01:39,272 --> 01:01:41,674
WEAK GAG-SPECIFIC CTL RESPONSES.

1780
01:01:41,674 --> 01:01:43,610
SO THE OVERARCHING PLAN HERE

1781
01:01:43,610 --> 01:01:45,245
ACROSS OUR COHORTS LISTED ON THE

1782
01:01:45,245 --> 01:01:47,113
BOTTOM OF THE SLIDE IS TO APPLY

1783
01:01:47,113 --> 01:01:50,149
THIS MULTIMODAL APPROACH WITH I

1784
01:01:50,149 --> 01:01:51,150
IMMUNOGENETICS TO REALLY

1785
01:01:51,150 --> 01:01:52,652
IDENTIFY CORRELATES OF SMALL

1786
01:01:52,652 --> 01:01:54,821
RESERVOIR SIZE AND IMMUNE

1787
01:01:54,821 --> 01:01:55,154
CONTROL.

1788
01:01:55,154 --> 01:01:56,990
NOW THE SECOND PART IS REALLY IN

1789
01:01:56,990 --> 01:01:58,191
THESE CHILDREN AND YOUNG ADULTS

1790
01:01:58,191 --> 01:02:03,196
WITH VERY LITTLE RESERVOIRS,

1791
01:02:03,196 --> 01:02:04,330
UNDERSTANDING WHAT CONTRIBUTES

1792
01:02:04,330 --> 01:02:05,832
TO REBOUND VIREMIA IS GOING TO

1793
01:02:05,832 --> 01:02:06,266
BE CRITICAL.

1794
01:02:06,266 --> 01:02:07,133
WE KNOW SOME OF THESE

1795
01:02:07,133 --> 01:02:08,334
INDIVIDUALS DO STOP THERAPY AND

1796
01:02:08,334 --> 01:02:08,635
DO REBOUND.

1797
01:02:08,635 --> 01:02:10,169
SO I DON'T KNOW THAT WE KNOW FOR

1798
01:02:10,169 --> 01:02:11,971
SURE THAT GETTING TO THIS

1799
01:02:11,971 --> 01:02:13,540
EXCEEDINGLY LOW LEVEL OF HIV

1800
01:02:13,540 --> 01:02:15,375
RESERVOIR SIZE IS ACTUALLY

1801
01:02:15,375 --> 01:02:18,244
PREDICTIVE OF REMISSION.

1802
01:02:18,244 --> 01:02:21,814
SO AS PART OF THIS, THIS GROUP

1803
01:02:21,814 --> 01:02:24,250
HAS OPTIMIZED IMMUNOCAPTURE

1804
01:02:24,250 --> 01:02:27,921
ASSAY AND ALSO ASSAYS TO

1805
01:02:27,921 --> 01:02:29,322
IDENTIFY PSEUDOVIRUS TESTING AND

1806
01:02:29,322 --> 01:02:30,857
TESTING THE SUSCEPTIBILITY OR

1807
01:02:30,857 --> 01:02:32,825
INFECTION CAPACITY IN PRIMARY

1808
01:02:32,825 --> 01:02:34,761
MACROPHAGES AND IN CELL LINES.

1809
01:02:34,761 --> 01:02:36,729
AND PRELIMINARY DATA TO DATE IN

1810
01:02:36,729 --> 01:02:39,365
THE REBOUND VIREMIA IN THE FAR

1811
01:02:39,365 --> 01:02:41,634
LEFT IN THE MISSISSIPPI BABY,

1812
01:02:41,634 --> 01:02:44,771
SHE HAS BEEN ABLE TO IDENTIFY --

1813
01:02:44,771 --> 01:02:46,439
AT THE TIME OF REBOUND VIREMIA.

1814
01:02:46,439 --> 01:02:47,540
SO THESE STUDIES WILL BE

1815
01:02:47,540 --> 01:02:49,909
EXPANDED TO OUR OTHER COHORTS

1816
01:02:49,909 --> 01:02:53,046
UNDERGOING  ATI TO ASSESS FOR

1817
01:02:53,046 --> 01:02:53,313
REMISSION.

1818
01:02:53,313 --> 01:02:56,549
THE LAST PART FOR RF1 THAT I

1819
01:02:56,549 --> 01:02:58,418
WANT TO FOCUS ON AND WE RECEIVED

1820
01:02:58,418 --> 01:03:01,888
AN OAR SUPPLEMENT TO EXPAND THE

1821
01:03:01,888 --> 01:03:02,655
CNS STUDY.

1822
01:03:02,655 --> 01:03:06,359
IN A PILOT STUDY IN THE IMPACT

1823
01:03:06,359 --> 01:03:08,628
NETWORK LED BY ANN CHAHROUDI

1824
01:03:08,628 --> 01:03:11,164
AND -- WAGNER IDENTIFIED 72% OF

1825
01:03:11,164 --> 01:03:12,799
YOUNG ADULTS LIVING WITH

1826
01:03:12,799 --> 01:03:15,501
PERINATAL INFECTION WHO HAD

1827
01:03:15,501 --> 01:03:17,904
NEUROCOGNITIVE IMPAIRMENT, HAD

1828
01:03:17,904 --> 01:03:19,272
CELL ASSOCIATED DNA DETECTED IN

1829
01:03:19,272 --> 01:03:20,540
THE CSF.

1830
01:03:20,540 --> 01:03:22,709
THE CSF DNA QUANTITATION WAS

1831
01:03:22,709 --> 01:03:25,211
DONE IN DOUG RICHMOND'S

1832
01:03:25,211 --> 01:03:25,645
LABORATORY.

1833
01:03:25,645 --> 01:03:26,746
SO WE BELIEVE IT'S REALLY

1834
01:03:26,746 --> 01:03:29,549
CRITICAL TO UNDERSTAND THE

1835
01:03:29,549 --> 01:03:32,185
PERSISTENCE OF CELLS IN THE CNS.

1836
01:03:32,185 --> 01:03:35,355
SO AS PART OF THIS ORA

1837
01:03:35,355 --> 01:03:37,624
SUPPLEMENT, THE SHARE TRIAL

1838
01:03:37,624 --> 01:03:38,725
GROUP ACTUALLY RECEIVED THE

1839
01:03:38,725 --> 01:03:41,894
SUPPLEMENT TO BEGIN TO DO CSF

1840
01:03:41,894 --> 01:03:43,296
STUDIES IN CHILDREN IN SOUTH

1841
01:03:43,296 --> 01:03:45,298
AFRICA LIVING WITH PERINATAL HIV

1842
01:03:45,298 --> 01:03:47,667
AND LONG TERM PERINATAL HIV.

1843
01:03:47,667 --> 01:03:50,103
AND THE MAIN POINT HERE IS

1844
01:03:50,103 --> 01:03:52,038
ACTUALLY TO BE ABLE TO PERFORM

1845
01:03:52,038 --> 01:03:53,106
CSF ON CHILDREN AND TRYING TO

1846
01:03:53,106 --> 01:03:55,108
BREAK DOWN THAT BARRIER AND FEAR

1847
01:03:55,108 --> 01:03:57,443
OF DOING SPINAL TAPS.

1848
01:03:57,443 --> 01:04:01,714
IT'S A NEW NEUROTROPIC VIRUS.

1849
01:04:01,714 --> 01:04:03,249
FOR ANY OTHER DISEASE, WE DO

1850
01:04:03,249 --> 01:04:05,318
SPINAL TAPS, AND WITH THIS

1851
01:04:05,318 --> 01:04:06,019
SUPPLEMENT, THEY'VE ACTUALLY

1852
01:04:06,019 --> 01:04:10,390
BEEN ABLE TO ENROLL 22 OF THE 45

1853
01:04:10,390 --> 01:04:11,858
PARTICIPANTS WITHIN MONTHS AT

1854
01:04:11,858 --> 01:04:13,526
THE ONE SITE THAT WAS

1855
01:04:13,526 --> 01:04:14,827
IRB-APPROVED.

1856
01:04:14,827 --> 01:04:15,962
THE SECOND SITE WHERE THE 23

1857
01:04:15,962 --> 01:04:16,963
PARTICIPANTS ARE COMING FROM

1858
01:04:16,963 --> 01:04:18,631
JUST RECEIVED IRB APPROVAL.

1859
01:04:18,631 --> 01:04:21,334
AND SO THIS IS REALLY TO KIND OF

1860
01:04:21,334 --> 01:04:22,969
EMPHASIZE THAT THESE STUDIES CAN

1861
01:04:22,969 --> 01:04:26,906
BE CARRIED OUT, CNS STUDIES OR

1862
01:04:26,906 --> 01:04:28,307
CSF ANALYSIS CAN BE CARRIED OUT

1863
01:04:28,307 --> 01:04:35,381
IN PEDIATRIC PARTICIPANTS.

1864
01:04:35,381 --> 01:04:36,949
A BEAUTIFUL WAY OF ENGAGING THE

1865
01:04:36,949 --> 01:04:39,085
COMMUNITY AND PARTICIPANTS ON

1866
01:04:39,085 --> 01:04:40,186
HOW BEST TO DO THESE STUDIES, SO

1867
01:04:40,186 --> 01:04:42,255
THEY HAVE A WHOLE MEDITATION

1868
01:04:42,255 --> 01:04:44,957
PACKAGE AND A LOT OF GOODIES

1869
01:04:44,957 --> 01:04:46,059
THAT THEY GIVE TO THE

1870
01:04:46,059 --> 01:04:47,694
PARTICIPANTS TO MAKE IT A VERY

1871
01:04:47,694 --> 01:04:48,728
COMFORTABLE ENVIRONMENT POST

1872
01:04:48,728 --> 01:04:49,629
SPINAL TAP ANALYSES.

1873
01:04:49,629 --> 01:04:50,930
SO WITH THIS STUDY, WE HOPE TO

1874
01:04:50,930 --> 01:04:53,666
BE ABLE TO COMPARE -- DO AN

1875
01:04:53,666 --> 01:04:55,268
EXTENSIVE PROFILING OF THE

1876
01:04:55,268 --> 01:04:56,602
PLASMA AND BLOOD USING

1877
01:04:56,602 --> 01:04:59,005
MULTI-OMICS APPROACHES, SINGLE

1878
01:04:59,005 --> 01:05:03,910
CELL RNA SEQ, AND DNA QUANTITY

1879
01:05:03,910 --> 01:05:04,911
TAKES -- CHARACTERIZATION, ET

1880
01:05:04,911 --> 01:05:06,412
CETERA, TO UNDERSTAND THE ROLE

1881
01:05:06,412 --> 01:05:10,450
OF DETECTING CSF DNA AND ITS

1882
01:05:10,450 --> 01:05:13,853
IMPLICATION FOR HIV PERSISTENCE.

1883
01:05:13,853 --> 01:05:16,355
SO FROM THIS SUMMARY FOR RF 1, I

1884
01:05:16,355 --> 01:05:18,424
HOPE I'VE CO CONVINCED YOU THAT

1885
01:05:18,424 --> 01:05:19,959
THERE ARE EXCEEDINGLY LOW LEVELS

1886
01:05:19,959 --> 01:05:23,062
OF RESERVOIRS IN EARLY TREATED

1887
01:05:23,062 --> 01:05:25,064
ADOLESCENTS THAT WE BELIEVE MORE

1888
01:05:25,064 --> 01:05:28,234
COMPREHENSIVE STUDIES INCLUDING

1889
01:05:28,234 --> 01:05:30,236
HLA AND KIR PHENOTYPING IS GOING

1890
01:05:30,236 --> 01:05:32,171
TO BE CRITICAL FOR UNDERSTANDING

1891
01:05:32,171 --> 01:05:33,339
OUTCOMES IN CHILDREN.

1892
01:05:33,339 --> 01:05:35,875
AND TO SEE IF STUDIES OF CSF ARE

1893
01:05:35,875 --> 01:05:37,510
FEASIBLE IN OUR PEDIATRIC

1894
01:05:37,510 --> 01:05:39,779
COHORTS THAT WILL INFORM OUR

1895
01:05:39,779 --> 01:05:40,346
CURE CLINICAL TRIALS.

1896
01:05:40,346 --> 01:05:41,881
SO FOR THIS COLLABORATORY, WE

1897
01:05:41,881 --> 01:05:43,216
DID PUT THE PLAIN LANGUAGE

1898
01:05:43,216 --> 01:05:44,817
SUMMARY AT THE END OF THE SLIDE,

1899
01:05:44,817 --> 01:05:46,219
BUT WHAT OUR KEY QUESTIONS WAS

1900
01:05:46,219 --> 01:05:49,055
THE EFFECTS OF EARLY ART ON

1901
01:05:49,055 --> 01:05:50,323
RESERVOIR SIZE, WHETHER THE

1902
01:05:50,323 --> 01:05:52,024
VIRAL AND HOST IMMUNE FACTORS

1903
01:05:52,024 --> 01:05:53,426
THAT MAY CONTRIBUTE TO CONTROL,

1904
01:05:53,426 --> 01:05:55,495
AND CAN WE DETECT SPECIFIC

1905
01:05:55,495 --> 01:05:57,029
BIOMARKERS IN THE BLOOD AND CNS

1906
01:05:57,029 --> 01:06:01,634
TO HELP US IDENTIFY REALLY

1907
01:06:01,634 --> 01:06:03,903
PREDICTIONS OF REMISSION.

1908
01:06:03,903 --> 01:06:06,706
SO I THINK WHAT SHOULD BE

1909
01:06:06,706 --> 01:06:07,640
ENCOURAGED IS THAT DRK AND WHAT

1910
01:06:07,640 --> 01:06:09,609
I WANT TO EMPHASIZE IS THE

1911
01:06:09,609 --> 01:06:10,610
CHARACTERISTICS OF THE RESERVOIR

1912
01:06:10,610 --> 01:06:11,511
IN CHILDREN AND YOUNG ADULTS

1913
01:06:11,511 --> 01:06:14,213
LIVING WITH PERINATAL HIV IS

1914
01:06:14,213 --> 01:06:16,048
REALLY INDEED DISTINCT AND WE

1915
01:06:16,048 --> 01:06:17,917
BELIEVE A FAVORABLE PLATFORM FOR

1916
01:06:17,917 --> 01:06:22,922
CURE THERAPEUTICS.

1917
01:06:22,922 --> 01:06:24,023
SO I'M GOING TO SWITCH TO THE

1918
01:06:24,023 --> 01:06:25,224
NEXT TWO COMPONENTS, WHICH IS RF

1919
01:06:25,224 --> 01:06:26,993
2 AND CONTROL OF REBOUND IMOWN.

1920
01:06:26,993 --> 01:06:31,130
THIS IS LED BY FILL I.P.

1921
01:06:31,130 --> 01:06:33,199
GOULDER, AND NOW MAURICIO

1922
01:06:33,199 --> 01:06:34,367
MARTINS WHO YOU'LL HEAR FROM

1923
01:06:34,367 --> 01:06:34,567
NEXT.

1924
01:06:34,567 --> 01:06:37,136
THIS IS REALLY FOCUSED ON

1925
01:06:37,136 --> 01:06:39,972
ENHANCING PEDIATRIC HIV IMMUNITY

1926
01:06:39,972 --> 01:06:41,841
INCLUDING USE OF VECTORED BNAB

1927
01:06:41,841 --> 01:06:43,442
DELIVERY TO ACHIEVE POST

1928
01:06:43,442 --> 01:06:43,910
TREATMENT CONTROL.

1929
01:06:43,910 --> 01:06:45,878
WE HOPE TO GAIN INSIGHTS INTO

1930
01:06:45,878 --> 01:06:47,380
IMMUNE MEDIATED CONTROL OR

1931
01:06:47,380 --> 01:06:49,782
VIROLOGIC CONTROL OF PERINATAL

1932
01:06:49,782 --> 01:06:50,316
HIV INFECTION.

1933
01:06:50,316 --> 01:06:53,152
THIS IS THE RF 2 TEAM.

1934
01:06:53,152 --> 01:06:54,487
AND SO THE FIRST STORY THAT I'M

1935
01:06:54,487 --> 01:06:59,058
GOING TO TELL IS DATA FROM PHIL

1936
01:06:59,058 --> 01:07:00,493
GOULDER'S GROUP IN SOUTH AFRICA,

1937
01:07:00,493 --> 01:07:01,928
WHERE HE HAS A BABY CURE PROJECT

1938
01:07:01,928 --> 01:07:04,530
THAT IS FUNDED BY THE NIH, AND

1939
01:07:04,530 --> 01:07:07,667
WHERE HE'S IDENTIFIED EARLY LIFE

1940
01:07:07,667 --> 01:07:10,203
IMMUNE SEX DIFFERENCES IN

1941
01:07:10,203 --> 01:07:12,104
PERINATAL INFECTION.

1942
01:07:12,104 --> 01:07:14,574
SO THIS STUDY AS I SAID IS

1943
01:07:14,574 --> 01:07:17,877
CARRIED OUT IN NATAL, AND IN

1944
01:07:17,877 --> 01:07:19,512
THIS BABY CURE STUDY, HE

1945
01:07:19,512 --> 01:07:21,314
FOLLOWED CLOSE TO 300

1946
01:07:21,314 --> 01:07:22,448
MOTHER-INFANT PAIRS IN INFANTS

1947
01:07:22,448 --> 01:07:26,819
WHO HAD ACQUIRED INFECTION,

1948
01:07:26,819 --> 01:07:28,855
RECEIVED EARLY THERAPY IN 2015

1949
01:07:28,855 --> 01:07:32,592
BASED ON THE REPORT OF THE

1950
01:07:32,592 --> 01:07:36,329
MISSISSIPPI BABY.

1951
01:07:36,329 --> 01:07:39,832
SO TREATED WITHIN ONE TO 11 DAYS

1952
01:07:39,832 --> 01:07:42,068
OF LIFE WITH COMBINATION

1953
01:07:42,068 --> 01:07:43,069
ANTIRETROVIRAL TERRITORIMENT.

1954
01:07:43,069 --> 01:07:46,505
TREATMENT.HE FOLLOWED THESE INFR

1955
01:07:46,505 --> 01:07:46,906
TIME.

1956
01:07:46,906 --> 01:07:48,307
IN THIS STUDY WHAT THEY DID

1957
01:07:48,307 --> 01:07:49,508
IDENTIFY, AND THIS HAS BEEN

1958
01:07:49,508 --> 01:07:50,743
PUBLISHED WITH SEX DIFFERENCES

1959
01:07:50,743 --> 01:07:51,677
IN PERINATAL INFECTIONS.

1960
01:07:51,677 --> 01:07:54,213
SO INTERESTINGLY, IN THE SETTING

1961
01:07:54,213 --> 01:07:56,082
OF ACUTE INFECTION IN MOTHERS,

1962
01:07:56,082 --> 01:07:58,217
MALES ARE LESS SUSCEPTIBLE TO

1963
01:07:58,217 --> 01:07:59,118
VERTICAL TRANSMISSION AND HE'S

1964
01:07:59,118 --> 01:08:00,319
ACTUALLY CARRIED THESE STUDIES

1965
01:08:00,319 --> 01:08:01,721
IN TWIN STUDIES AND DEMONSTRATED

1966
01:08:01,721 --> 01:08:04,457
THAT IT ALSO EXISTS IN TWIN

1967
01:08:04,457 --> 01:08:05,658
PREGNANCIES.

1968
01:08:05,658 --> 01:08:07,026
AND HE'S ESTABLISHED THAT THIS

1969
01:08:07,026 --> 01:08:10,563
IS ACTUALLY DUE TO EARLY LIFE

1970
01:08:10,563 --> 01:08:11,864
INNATE IMMUNE SEX DIFFERENCES SO

1971
01:08:11,864 --> 01:08:14,500
GIRLS ARE MORE LIKELY TO BE

1972
01:08:14,500 --> 01:08:15,902
INFECTED IN UTERO, ALSO MORE

1973
01:08:15,902 --> 01:08:17,436
LIKELY TO BE INFECTED WITH

1974
01:08:17,436 --> 01:08:19,772
INTERFERON RESISTANT VARIANTS

1975
01:08:19,772 --> 01:08:27,280
WHEREAS BOYS LESS U.S.

1976
01:08:27,280 --> 01:08:28,681
SEPTEMBER -- WHAT HE IDENTIFIED

1977
01:08:28,681 --> 01:08:31,951
WAS VIRAL REBOUND IS LESS

1978
01:08:31,951 --> 01:08:35,354
FREQUENT IN ART NON-ADHERENT

1979
01:08:35,354 --> 01:08:37,089
MALES.

1980
01:08:37,089 --> 01:08:39,926
STHIS IS A VERY BUSY SLIDE, AGAN

1981
01:08:39,926 --> 01:08:41,227
THIS IS SORT OF A HIGH LEVEL

1982
01:08:41,227 --> 01:08:41,560
OVERVIEW.

1983
01:08:41,560 --> 01:08:42,862
THIS SHOWS THE FIVE MALE

1984
01:08:42,862 --> 01:08:43,195
PARTICIPANTS.

1985
01:08:43,195 --> 01:08:45,598
IF YOU COULD JUST FOCUS ON THE

1986
01:08:45,598 --> 01:08:47,433
RED TRIANGLES IN THE BOTTOM AND

1987
01:08:47,433 --> 01:08:49,702
THEN THE BLUE ARROWS GOING UP

1988
01:08:49,702 --> 01:08:51,971
AND DOWN, IT JUST SHOWS YOU THAT

1989
01:08:51,971 --> 01:08:53,906
THE VIRAL LOAD REMAINS

1990
01:08:53,906 --> 01:08:56,542
UNDETECTABLE IN ALL FIVE MALE

1991
01:08:56,542 --> 01:08:59,145
PARTICIPANTS, EVEN THOUGH THE

1992
01:08:59,145 --> 01:09:02,748
LEVELS OF LOPINAVIR WHICH IS

1993
01:09:02,748 --> 01:09:04,283
SHOWN IN THE BLUE LINE WITH THE

1994
01:09:04,283 --> 01:09:06,218
TRIANGLE FALLS BELOW THERAPEUTIC

1995
01:09:06,218 --> 01:09:06,452
LEVELS.

1996
01:09:06,452 --> 01:09:07,987
SO BASED ON THIS CONFIRMING BY

1997
01:09:07,987 --> 01:09:10,289
DRUG LEVEL MONITORING, THEY WERE

1998
01:09:10,289 --> 01:09:11,958
ABLE TO IDENTIFY FIVE MALES IN

1999
01:09:11,958 --> 01:09:14,360
THIS COHORT OF -- I THINK HE

2000
01:09:14,360 --> 01:09:17,930
REPORTED IT WAS 286 IN THE FINAL

2001
01:09:17,930 --> 01:09:22,034
ANALYSIS.

2002
01:09:22,034 --> 01:09:23,035
WHO EXPERIENCED THIS LACK OF

2003
01:09:23,035 --> 01:09:25,771
REBOUND IN THE SETTING OF

2004
01:09:25,771 --> 01:09:30,142
NON-DETECTABLE ARV

2005
01:09:30,142 --> 01:09:30,576
CONCENTRATIONS.

2006
01:09:30,576 --> 01:09:34,046
BASED ON THIS, HE'S CONCLUDING

2007
01:09:34,046 --> 01:09:37,550
THAT MALES ARE MORE LIKELY TO

2008
01:09:37,550 --> 01:09:39,618
ACHIEVE AVIREMIA WITH VERY EARLY

2009
01:09:39,618 --> 01:09:41,821
ANTIRETROVIRAL TREATMENT.

2010
01:09:41,821 --> 01:09:43,322
HE'S SHOWN -- IN AN INTEREST OF

2011
01:09:43,322 --> 01:09:44,423
TIME I DIDN'T SHOW THE DATA --

2012
01:09:44,423 --> 01:09:45,758
THAT THIS IS ACTUALLY ASSOCIATED

2013
01:09:45,758 --> 01:09:47,693
WITH TRANSMISSION OF LOW FITNESS

2014
01:09:47,693 --> 01:09:52,832
VIRUS IN THESE FIVE INFANTS.

2015
01:09:52,832 --> 01:09:55,568
SO ESSENTIALLY THE PRIMARY

2016
01:09:55,568 --> 01:09:57,536
CONCLUSION IS THAT EARLY LIFE

2017
01:09:57,536 --> 01:09:59,171
INNATE IMMUNE SEX DIFFERENCES DO

2018
01:09:59,171 --> 01:10:00,373
MODULATE VERTICAL TRANSMISSION

2019
01:10:00,373 --> 01:10:01,874
AND INFLUENCE OUTCOME POST

2020
01:10:01,874 --> 01:10:02,775
TRANSMISSION.

2021
01:10:02,775 --> 01:10:04,710
I DON'T THINK WE HAD CONSIDERED

2022
01:10:04,710 --> 01:10:07,780
SEX DIFFERENCES IN TERMS OF CURE

2023
01:10:07,780 --> 01:10:08,981
POTENTIAL PRIOR TO THESE

2024
01:10:08,981 --> 01:10:09,448
STUDIES.

2025
01:10:09,448 --> 01:10:13,352
I WILL SAY IN OUR IMPACT EARLY

2026
01:10:13,352 --> 01:10:15,254
TREATMENT WE FOUND SIMILARLY

2027
01:10:15,254 --> 01:10:17,723
GIRLS WERE LESS LIKELY TO

2028
01:10:17,723 --> 01:10:19,191
ACHIEVE VIROLOGIC SUPPRESSION BY

2029
01:10:19,191 --> 01:10:21,327
48 WEEKS, BY 2 YEARS OF AGE

2030
01:10:21,327 --> 01:10:21,994
COMPARED TO MALES.

2031
01:10:21,994 --> 01:10:24,163
SO THERE ARE EMERGING DATA IN

2032
01:10:24,163 --> 01:10:26,799
TERMS OF SEX DIFFERENCES WITH

2033
01:10:26,799 --> 01:10:28,434
RESPECT TO INFECTION

2034
01:10:28,434 --> 01:10:30,936
SUSCEPTIBILITY AND IN LONG-TERM

2035
01:10:30,936 --> 01:10:32,171
VIROLOGIC SUPPRESSION,

2036
01:10:32,171 --> 01:10:33,105
HIGHLIGHTING THE NEED TO

2037
01:10:33,105 --> 01:10:34,774
CONSIDER SEX-SPECIFIC

2038
01:10:34,774 --> 01:10:36,609
INTERVENTIONS TO OPTIMIZE CURE

2039
01:10:36,609 --> 01:10:38,911
POTENTIAL IN CHILDREN.

2040
01:10:38,911 --> 01:10:40,112
LASTLY, I WANT TO JUST KIND OF

2041
01:10:40,112 --> 01:10:41,313
HIGHLIGHT THE TISSUE RESERVOIR

2042
01:10:41,313 --> 01:10:41,647
STUDY.

2043
01:10:41,647 --> 01:10:43,716
SO WE'VE BEGUN STUDIES ON THE

2044
01:10:43,716 --> 01:10:46,652
CNS THROUGH CSF SAMPLING

2045
01:10:46,652 --> 01:10:50,122
OBVIOUSLY, BUT WE HAVE A REALLY

2046
01:10:50,122 --> 01:10:54,493
TERRIFIC GROUP WHO HAVE WORKED

2047
01:10:54,493 --> 01:10:56,829
FOR YEARS COLLECTING TONSILS.

2048
01:10:56,829 --> 01:10:58,664
WHEN YOU HAVE A BIOBANK OF

2049
01:10:58,664 --> 01:11:01,400
TONSILS, OVER 300 TONSILS FROM

2050
01:11:01,400 --> 01:11:04,336
CHILDREN AND ADULTS ONE YEAR OF

2051
01:11:04,336 --> 01:11:06,172
AGE TO 50-PLUS YEARS OF AGE

2052
01:11:06,172 --> 01:11:08,340
LIVING WITH AND WITHOUT HIV IN

2053
01:11:08,340 --> 01:11:09,775
SOUTH AFRICA.

2054
01:11:09,775 --> 01:11:12,311
SO A VERY RICH BIOBANK TO ASSESS

2055
01:11:12,311 --> 01:11:14,747
THE TONSIL TISSUE RESERVOIR IN

2056
01:11:14,747 --> 01:11:16,549
PERINATAL AND ADULT INFECTIONS,

2057
01:11:16,549 --> 01:11:18,651
SO PROVIDES A REALLY BEAUTIFUL

2058
01:11:18,651 --> 01:11:20,386
PLATFORM TO COMPARE ACROSS THE

2059
01:11:20,386 --> 01:11:24,323
AIDS SPECTRUM TISSUE RESERVOIRS.

2060
01:11:24,323 --> 01:11:25,758
AND SO PRELIMINARY DATA FROM

2061
01:11:25,758 --> 01:11:27,159
THIS GROUP, WHAT YOU SEE ON THE

2062
01:11:27,159 --> 01:11:29,962
FAR LEFT IS THAT THIS IS AGE AT

2063
01:11:29,962 --> 01:11:31,764
THE BOTTOM AND YOU CAN SEE

2064
01:11:31,764 --> 01:11:33,833
PERCENT CD4s ARE NOT DIFFERENT

2065
01:11:33,833 --> 01:11:35,167
IN TONSILS IN CHILDREN COMPARED

2066
01:11:35,167 --> 01:11:36,769
WITH ADULTS AS SHOWN IN GREEN.

2067
01:11:36,769 --> 01:11:38,637
BUT WHEN YOU LOOK AT T

2068
01:11:38,637 --> 01:11:40,506
FOLLICULAR HELPER CELLS IN THE

2069
01:11:40,506 --> 01:11:42,575
TONSILS, KIDS HAVE HIGHER

2070
01:11:42,575 --> 01:11:45,544
PROPORTIONS OF T FOLLICULAR

2071
01:11:45,544 --> 01:11:47,480
HELPER CELLS AND IN THE

2072
01:11:47,480 --> 01:11:48,481
CORRELATION PLOT, YOU CAN SEE

2073
01:11:48,481 --> 01:11:50,549
THIS IS DEFINITELY AN

2074
01:11:50,549 --> 01:11:51,750
AGE-DEPENDENT EFFECT, AND

2075
01:11:51,750 --> 01:11:53,185
ALSO -- BUT ADULTS HAD HIGHER

2076
01:11:53,185 --> 01:11:57,223
LEVELS OF CCR-5 EXPRESSION IN

2077
01:11:57,223 --> 01:11:58,624
THEIR TONSILS THAN IN PEDIATRIC

2078
01:11:58,624 --> 01:11:58,824
CASES.

2079
01:11:58,824 --> 01:12:00,659
THEY HAVE MULTIPLE STUDIES

2080
01:12:00,659 --> 01:12:02,128
PLANNED AND HOPEFULLY THE NEXT

2081
01:12:02,128 --> 01:12:03,696
STRATEGIES FOR CURE, WE'LL HAVE

2082
01:12:03,696 --> 01:12:05,531
SOME IN DEPTH RESULTS HERE, BUT

2083
01:12:05,531 --> 01:12:08,701
JUST TO SAY THAT THIS IS AN

2084
01:12:08,701 --> 01:12:10,803
EXTENSIVE PROJECT THAT WAS

2085
01:12:10,803 --> 01:12:15,608
ALSO -- RECEIVED A SUPPLEMENT,

2086
01:12:15,608 --> 01:12:16,809
OAR SUPPLEMENT FOR STUDIES.

2087
01:12:16,809 --> 01:12:18,077
SO OUR PLAIN LANGUAGE SUMMARY

2088
01:12:18,077 --> 01:12:19,745
FOR THIS, AND THEN I'LL TURN IT

2089
01:12:19,745 --> 01:12:20,980
OVER TO MAURICIO, IS WHAT ARE

2090
01:12:20,980 --> 01:12:22,248
THE KEY QUESTIONS, REALLY

2091
01:12:22,248 --> 01:12:23,782
OBVIOUSLY WHAT ARE THE IMMUNE

2092
01:12:23,782 --> 01:12:24,550
FACTORS THAT DRIVE SEX

2093
01:12:24,550 --> 01:12:25,885
DIFFERENCES IN HIV CONTROL IN

2094
01:12:25,885 --> 01:12:27,753
CHILDREN.

2095
01:12:27,753 --> 01:12:29,155
IS HIV LOCATED IN DIFFERENT

2096
01:12:29,155 --> 01:12:30,322
LYMPHOID TISSUE SITES IN

2097
01:12:30,322 --> 01:12:31,757
CHILDREN COMPARED TO ADULTS

2098
01:12:31,757 --> 01:12:33,526
LIVING WITH HIV, HOW DO THOSE

2099
01:12:33,526 --> 01:12:35,394
DIFFER, AND CAN WE ENHANCE

2100
01:12:35,394 --> 01:12:37,029
ANTIVIRAL IMMUNITY IN CHILDREN

2101
01:12:37,029 --> 01:12:39,331
THROUGH STUDYING ON THIS EXPLANT

2102
01:12:39,331 --> 01:12:41,600
MODEL, TONSILLAR MODEL FOR

2103
01:12:41,600 --> 01:12:42,801
IMMUNE INTERVENTIONS.

2104
01:12:42,801 --> 01:12:45,738
WE BELIEVE THESE STUDIES ALL

2105
01:12:45,738 --> 01:12:46,739
TOGETHER HIGHLIGHTING

2106
01:12:46,739 --> 01:12:48,474
DIFFERENCES IN PEDIATRIC AND

2107
01:12:48,474 --> 01:12:53,279
ADULT INFECTIONS REQUIRING

2108
01:12:53,279 --> 01:12:54,713
CONTINUED INVESTIGATION OF THESE

2109
01:12:54,713 --> 01:12:55,915
DIFFERENT AREAS OF HIV

2110
01:12:55,915 --> 01:12:59,852
PERSISTENCE.

2111
01:12:59,852 --> 01:13:04,990
THIS IS THE TEAM OF HENRY AND

2112
01:13:04,990 --> 01:13:06,525
ZACH, AND I'LL TURN IT OVER TO

2113
01:13:06,525 --> 01:13:08,294
MAURICIO TO TALK ABOUT AAV

2114
01:13:08,294 --> 01:13:09,795
EXPRESSION OF COMBINATION BNABS

2115
01:13:09,795 --> 01:13:10,896
AND VIROLOGIC CONTROL.

2116
01:13:10,896 --> 01:13:21,073
[APPLAUSE]

2117
01:13:21,473 --> 01:13:26,946
>> MY GROUP IS INTERESTED
- -- E

2118
01:13:26,946 --> 01:13:27,713
MOLECULES WE'RE USING FOR THE

2119
01:13:27,713 --> 01:13:31,750
STUDY ARE THE B3 GLYCAN -- AND

2120
01:13:31,750 --> 01:13:38,657
THE I MEUB -- WE ALSO THINK OF

2121
01:13:38,657 --> 01:13:40,092
PASSIVE IMMY ?AITION HOLDS GREAT

2122
01:13:40,092 --> 01:13:42,695
PROMISE FOR TREATING PEDIATRIC

2123
01:13:42,695 --> 01:13:44,463
HIV INFECTION BECAUSE THESE

2124
01:13:44,463 --> 01:13:49,034
MOLECULES ARE SAFE, IN INFANTS,

2125
01:13:49,034 --> 01:13:50,035
INCLUDING -- CHILDREN INCLUDING

2126
01:13:50,035 --> 01:13:52,538
INFANTS AND ALSO THEY HAVE

2127
01:13:52,538 --> 01:13:55,608
DEMONSTRATED -- NOT ONLY IN HIV

2128
01:13:55,608 --> 01:13:56,809
STUDY BUS ALSO IN CLINICAL

2129
01:13:56,809 --> 01:13:57,042
STUDIES.

2130
01:13:57,042 --> 01:13:58,244
BUT THERE IS A CAVEAT.

2131
01:13:58,244 --> 01:13:59,545
THE MAIN ONE THAT WE THINK IS

2132
01:13:59,545 --> 01:14:01,947
BECAUSE THE CURRENT PARADIGM FOR

2133
01:14:01,947 --> 01:14:04,250
DELIVERING THESE MOLECULES

2134
01:14:04,250 --> 01:14:05,985
REQUIRE PASSIVE DELIVERY,

2135
01:14:05,985 --> 01:14:07,519
REPEATED PASSIVE DELIVERY WHICH

2136
01:14:07,519 --> 01:14:09,388
FACES BOTH LOGISTICAL AND

2137
01:14:09,388 --> 01:14:11,023
ECONOMICAL CHALLENGES FROM BROAD

2138
01:14:11,023 --> 01:14:12,324
SCALE IMPLEMENTATION.

2139
01:14:12,324 --> 01:14:15,160
WHAT IF WE COULD ENGINEER HOST

2140
01:14:15,160 --> 01:14:16,495
CELLS TO CONTINUOUSLY PRODUCE

2141
01:14:16,495 --> 01:14:18,564
THESE MOLECULES, THEREBY

2142
01:14:18,564 --> 01:14:20,199
OBVIATING THE NEED FOR THESE

2143
01:14:20,199 --> 01:14:20,833
REPEATED ADMINISTRATIONS.

2144
01:14:20,833 --> 01:14:22,067
SO THIS IS EXACTLY WHAT WE'RE

2145
01:14:22,067 --> 01:14:24,036
TRYING TO ACHIEVE WITH GENE

2146
01:14:24,036 --> 01:14:25,804
THERAPY USING AAV VECTORS.

2147
01:14:25,804 --> 01:14:31,043
WE'RE INTERESTED IN -- SKELETAL

2148
01:14:31,043 --> 01:14:32,244
CELLS BECAUSE THEY HAVE A VERY

2149
01:14:32,244 --> 01:14:34,079
LONG LIFESPAN, AND AS LONG AS

2150
01:14:34,079 --> 01:14:36,615
THE -- SO THE AAV GENOME

2151
01:14:36,615 --> 01:14:39,985
PERSISTS IN THE CELL NUCLEUS

2152
01:14:39,985 --> 01:14:41,086
FOR -- BASICALLY FOR AS LONG AS

2153
01:14:41,086 --> 01:14:43,489
THE CELL LIVES, SO IF YOU DON'T

2154
01:14:43,489 --> 01:14:45,257
HAVE ANY IMMUNE RESPONSE, IF

2155
01:14:45,257 --> 01:14:48,761
IT'S NOT TOXIC YOU CAN

2156
01:14:48,761 --> 01:14:50,496
ESSENTIALLY GET PERSISTENT --

2157
01:14:50,496 --> 01:14:52,464
FOR YEARS AND POSSIBLY DECADES.

2158
01:14:52,464 --> 01:14:53,999
OUR VISION IS FOLLOWING A SINGLE

2159
01:14:53,999 --> 01:14:55,634
DOSE OF AAV VECTORS, CHILDREN

2160
01:14:55,634 --> 01:14:57,736
LIVING WITH HIV WOULD DEVELOP

2161
01:14:57,736 --> 01:14:59,138
PERSISTENT ECK PRETION OF THESE

2162
01:14:59,138 --> 01:15:01,006
HIV BIOLOGICS AT SUFFICIENT

2163
01:15:01,006 --> 01:15:03,075
LEVELS TO PREVENT VIRUS REBOUND

2164
01:15:03,075 --> 01:15:04,176
AFTER ART INTERRUPTION.

2165
01:15:04,176 --> 01:15:08,280
SO TO TEST THIS, WE PARTNERED AT

2166
01:15:08,280 --> 01:15:09,648
THE OREGON NATIONAL HIGH PRAIT

2167
01:15:09,648 --> 01:15:18,991
CENTPRIMATECENTER, WE ENROLLED ,

2168
01:15:18,991 --> 01:15:20,092
SEVEN DAYS LATER THESE ANIMALS

2169
01:15:20,092 --> 01:15:22,361
WERE STARTED ON ANTIRETROVIRAL

2170
01:15:22,361 --> 01:15:23,662
THERAPY AND AT THE SAME TIME,

2171
01:15:23,662 --> 01:15:26,632
THEY RECEIVED FOUR INTRAMUSCULAR

2172
01:15:26,632 --> 01:15:31,337
INJECTIONS OF AAV9 VECTORS

2173
01:15:31,337 --> 01:15:33,539
ENCODING -- OR -- SO THESE

2174
01:15:33,539 --> 01:15:35,007
INTERVENTIONS WERE GIVEN AT DAY

2175
01:15:35,007 --> 01:15:36,842
SEVEN AND THEY WERE DELIVERED IN

2176
01:15:36,842 --> 01:15:37,810
FOUR INTRAMUSCULAR INJECTIONS.

2177
01:15:37,810 --> 01:15:38,243
THAT'S IT.

2178
01:15:38,243 --> 01:15:39,778
AT THE SAME LOCATION.

2179
01:15:39,778 --> 01:15:42,214
IN PARALLEL, WE ALSO INFECTED

2180
01:15:42,214 --> 01:15:44,483
THREE CONTROLS FOR VARIOUS

2181
01:15:44,483 --> 01:15:45,684
REASONS WE COULDN'T ADD

2182
01:15:45,684 --> 01:15:46,985
ADDITIONAL CONTROL ANIMALS IN

2183
01:15:46,985 --> 01:15:49,154
THE 2022 COHORT SO WE ADDED

2184
01:15:49,154 --> 01:15:50,389
THREE MORE THIS YEAR AND THESE

2185
01:15:50,389 --> 01:15:51,390
ANIMALS ARE BEING MONITORED.

2186
01:15:51,390 --> 01:15:54,426
SO LET'S LOOK AT THE PRE-ATI

2187
01:15:54,426 --> 01:15:57,396
PHASE.

2188
01:15:57,396 --> 01:15:58,464
I'M GOING TO BE SHOWING THESE

2189
01:15:58,464 --> 01:16:01,433
GRAPHS FOR THE NEXT FEW SLIDES

2190
01:16:01,433 --> 01:16:04,069
TO RED DOTS ARE PLASMA VIRAL

2191
01:16:04,069 --> 01:16:04,269
LOADS.

2192
01:16:04,269 --> 01:16:07,673
THE SHADED AREA CORRESPONDS TO

2193
01:16:07,673 --> 01:16:09,842
THE ANTIRETROVIRAL THERAPY

2194
01:16:09,842 --> 01:16:10,609
PHASE.

2195
01:16:10,609 --> 01:16:12,411
SO ART SUPPRESSED VIRAL LOADS IN

2196
01:16:12,411 --> 01:16:14,780
BOTH THE CONTROLS AND THE

2197
01:16:14,780 --> 01:16:20,819
EXPERIMENTAL ANIMALS.

2198
01:16:20,819 --> 01:16:23,789
I'M GOING TO SHOW YOU THE SERUM

2199
01:16:23,789 --> 01:16:25,758
CONCENTRATION LEVELS, YELLOW

2200
01:16:25,758 --> 01:16:29,461
DOTS WILL BE 10-1074, GREEN

2201
01:16:29,461 --> 01:16:31,130
DOTS -- SO ALL EXPERIMENTAL

2202
01:16:31,130 --> 01:16:34,967
ANIMALS DEVELOPED PERSISTENT

2203
01:16:34,967 --> 01:16:36,802
EXPRESSION -- WAS A BIT MORE

2204
01:16:36,802 --> 01:16:38,437
VARIABLE WITH A FEW INSTANCES OF

2205
01:16:38,437 --> 01:16:41,740
LOSS AND INTERESTINGLY REGAIN OF

2206
01:16:41,740 --> 01:16:44,576
EXPRESSION.

2207
01:16:44,576 --> 01:16:46,211
WHAT HAPPENED AFTER WE STOPPED

2208
01:16:46,211 --> 01:16:46,779
ART?

2209
01:16:46,779 --> 01:16:49,415
CONTROLS REBOUNDED, ALL THREE OF

2210
01:16:49,415 --> 01:16:52,117
THEM, VERY EASILY DETECTABLE.

2211
01:16:52,117 --> 01:16:54,186
VIRAL LOADS AT WEEK TWO, POST

2212
01:16:54,186 --> 01:16:57,256
INFECTION.

2213
01:16:57,256 --> 01:16:58,891
AND ALL ANIMALS MAINTAINED

2214
01:16:58,891 --> 01:17:00,159
EXPRESSION OF AT LEAST ONE OF

2215
01:17:00,159 --> 01:17:01,193
THE MOLECULES THROUGHOUT THE

2216
01:17:01,193 --> 01:17:02,060
POST ATI PHASE.

2217
01:17:02,060 --> 01:17:05,364
I'M GOING TO HE FOCUS ON SEVEN

2218
01:17:05,364 --> 01:17:06,331
ANIMALS BECAUSE THEY WERE

2219
01:17:06,331 --> 01:17:06,632
REMARKABLE.

2220
01:17:06,632 --> 01:17:08,267
THERE WAS NO REBOUND IN SEVEN OF

2221
01:17:08,267 --> 01:17:09,835
THEM FOR THE HUNDREDS OF TIME

2222
01:17:09,835 --> 01:17:12,304
POINTS THAT WE MEASURED SO FAR.

2223
01:17:12,304 --> 01:17:13,939
SO IN ALL CASES WHERE REBOUND

2224
01:17:13,939 --> 01:17:17,309
WAS PREVENTED OR DELAYED, IN THE

2225
01:17:17,309 --> 01:17:22,548
NEXT FEW CASES, BOTH ECD4IG AND

2226
01:17:22,548 --> 01:17:25,751
THE 1074 WERE STABLY EXPRESSED

2227
01:17:25,751 --> 01:17:28,253
WITH POST ATI AVERAGES IN EACH

2228
01:17:28,253 --> 01:17:32,624
ANIMAL WITH 15 TO 33 OR 19 TO 76

2229
01:17:32,624 --> 01:17:35,294
MICRO GRAMS PER ML FOR 10-1074.

2230
01:17:35,294 --> 01:17:38,197
THERE WAS THIS ONE ANIMAL THAT

2231
01:17:38,197 --> 01:17:39,531
EXPERIENCED CONSECUTIVE EPISODES

2232
01:17:39,531 --> 01:17:41,733
OF LOW LEVEL VIREMIA AT ABOUT

2233
01:17:41,733 --> 01:17:47,739
WEEK 30 POST ATI.

2234
01:17:47,739 --> 01:17:50,909
THEN VIRUS REBOUND COINCIDED

2235
01:17:50,909 --> 01:17:54,646
WITH A DROP -- ADJUVANT WAS

2236
01:17:54,646 --> 01:17:55,280
MAINTAINED THROUGHOUT THIS

2237
01:17:55,280 --> 01:17:57,416
PERIOD AND THAT PROBABLY HELPED

2238
01:17:57,416 --> 01:17:58,884
THIS ANIMAL REGAIN CONTROL IN

2239
01:17:58,884 --> 01:18:02,521
THE NEXT FEW TIME POINTS.

2240
01:18:02,521 --> 01:18:06,658
A FEW OF THE EXPERIMENTAL

2241
01:18:06,658 --> 01:18:07,860
ANIMALS EXPERIENCED REBOUND POST

2242
01:18:07,860 --> 01:18:13,565
ATI AND IN THOSE CASES ONLY --

2243
01:18:13,565 --> 01:18:16,268
BUT THAT MOLECULE, THE

2244
01:18:16,268 --> 01:18:17,069
PERSISTENT EXPRESSION PROBABLY

2245
01:18:17,069 --> 01:18:19,671
CONTRIBUTED TO REGAIN OF CONTROL

2246
01:18:19,671 --> 01:18:21,773
IN THOSE TWO INSTANCES.

2247
01:18:21,773 --> 01:18:24,276
TO OUR SURPRISE, 10-1074

2248
01:18:24,276 --> 01:18:25,477
EXPRESSION REBOUNDED IN THE TWO

2249
01:18:25,477 --> 01:18:28,547
ANIMALS AT WEEKS 2 TO 22 POST

2250
01:18:28,547 --> 01:18:29,882
ATI AND THIS INCREASE IN

2251
01:18:29,882 --> 01:18:31,750
CONCENTRATIONS OF 10-1074

2252
01:18:31,750 --> 01:18:33,151
COINCIDED WITH REGAIN OF

2253
01:18:33,151 --> 01:18:33,919
VIROLOGIC CONTROL.

2254
01:18:33,919 --> 01:18:39,491
SO WHEN WE PLOTTED THIS I,

2255
01:18:39,491 --> 01:18:40,726
PREVENTION OR DELAY OF VIRUS

2256
01:18:40,726 --> 01:18:42,361
REBOUND WAS STATISTICALLY

2257
01:18:42,361 --> 01:18:42,794
SIGNIFICANT.

2258
01:18:42,794 --> 01:18:45,764
SO WHEN YOU TRY AAV MEDIATED

2259
01:18:45,764 --> 01:18:47,833
GENE THERAPY WITH BROAD

2260
01:18:47,833 --> 01:18:49,368
NEUTRALIZING ANTIBODIES IN ADULT

2261
01:18:49,368 --> 01:18:52,538
MACAQUES, YOU OFTEN SEE -- TO

2262
01:18:52,538 --> 01:18:55,707
LIMIT THE EGGS PRETIO EGGS PRETE

2263
01:18:55,707 --> 01:18:56,141
MOLECULES.

2264
01:18:56,141 --> 01:18:57,809
THE HOST WILL DEVELOP ANTIBODIES

2265
01:18:57,809 --> 01:18:59,111
AGAINST THE AAV DELIVERED

2266
01:18:59,111 --> 01:18:59,645
MOLECULES.

2267
01:18:59,645 --> 01:19:01,213
BUT WE DON'T SEE THAT VERY

2268
01:19:01,213 --> 01:19:02,848
OFTEN.

2269
01:19:02,848 --> 01:19:04,917
ACTUALLY IN MOST CASES WE DON'T

2270
01:19:04,917 --> 01:19:06,785
SEE THAT AT ALL WITH INFANT

2271
01:19:06,785 --> 01:19:07,052
MACAQUES.

2272
01:19:07,052 --> 01:19:08,387
THE YOUNGER THEY ARE, THE LESS

2273
01:19:08,387 --> 01:19:10,589
LIKELY THEY ARE TO MAKE ADA

2274
01:19:10,589 --> 01:19:11,323
RESPONSES.

2275
01:19:11,323 --> 01:19:13,458
SO HERE EACH COLUMN CORRESPONDS

2276
01:19:13,458 --> 01:19:14,092
TO ONE ANIMAL.

2277
01:19:14,092 --> 01:19:16,395
AGAIN THE GREEN DOTS PLOTTED ON

2278
01:19:16,395 --> 01:19:19,998
THE LEFT, Y AXIS NOW, GREEN OR

2279
01:19:19,998 --> 01:19:22,200
YELLOW DOTS CORRESPONDS TO SERUM

2280
01:19:22,200 --> 01:19:24,169
CONCENTRATIONS OF EACH MOLECULE,

2281
01:19:24,169 --> 01:19:26,672
AND ON THE RIGHT Y AXIS, YOU

2282
01:19:26,672 --> 01:19:28,173
HAVE ABSORBANCE LEVELS OF

2283
01:19:28,173 --> 01:19:30,075
ANTIBODIES IN SERUM TARGETING

2284
01:19:30,075 --> 01:19:32,711
EACH BIOLOGIC.

2285
01:19:32,711 --> 01:19:34,580
AND THE ADAs IN THIS CASE ARE

2286
01:19:34,580 --> 01:19:36,448
PLOTTED IN BLACK DOTS.

2287
01:19:36,448 --> 01:19:38,016
THE HIGHER THE ADAs, TYPICALLY

2288
01:19:38,016 --> 01:19:39,051
THE LOWER EXPRESSION.

2289
01:19:39,051 --> 01:19:42,120
SO THESE LINES WERE FLAT IN THE

2290
01:19:42,120 --> 01:19:43,789
NEXT -- IN THE FIRST FIVE

2291
01:19:43,789 --> 01:19:45,324
ANIMALS THAT WE ANALYZED WITH

2292
01:19:45,324 --> 01:19:48,827
BRIEF INCREASES SHORTLY AFTER

2293
01:19:48,827 --> 01:19:50,796
INOCULATION BUT THEN THE ADAs

2294
01:19:50,796 --> 01:19:51,997
WENT BACK TO BASELINE.

2295
01:19:51,997 --> 01:19:54,399
WE SAW INSTANCES OF ADAs IN A

2296
01:19:54,399 --> 01:19:56,802
FEW ANIMALS, BUT INTERESTINGLY,

2297
01:19:56,802 --> 01:19:57,569
THEY DECAYED.

2298
01:19:57,569 --> 01:20:03,475
THEY FELL BACK TO BASELINE,

2299
01:20:03,475 --> 01:20:05,277
WHICH ENABLED A RECURRENCE IN

2300
01:20:05,277 --> 01:20:07,012
EXPRESSION LEVELS OF 10-1074 IN

2301
01:20:07,012 --> 01:20:07,546
THIS CASE.

2302
01:20:07,546 --> 01:20:09,247
SO THE VIROLOGIC CONTROL THAT I

2303
01:20:09,247 --> 01:20:12,184
JUST SHOWED YOU IS PROMISING BUT

2304
01:20:12,184 --> 01:20:16,455
WE NEED TO KEEP IN MIND THAT WE

2305
01:20:16,455 --> 01:20:17,556
STARTED ANTIRETROVIRAL THERAPY

2306
01:20:17,556 --> 01:20:18,690
VERY EARLY AFTER INFECTION ON

2307
01:20:18,690 --> 01:20:20,726
DAY 7 SO THAT PROBABLY LIMITS

2308
01:20:20,726 --> 01:20:22,260
THE SEEDING OF THE VIRAL

2309
01:20:22,260 --> 01:20:22,594
RESERVOIR.

2310
01:20:22,594 --> 01:20:24,129
WITH THAT IN MIND, WE'RE ASKING

2311
01:20:24,129 --> 01:20:28,934
IF EARLY ART INITIATION PLUS AAV

2312
01:20:28,934 --> 01:20:31,336
DELIVERY WILL ALSO EVENT VIRUS

2313
01:20:31,336 --> 01:20:35,841
REBOUND IN SHIV INFECTED

2314
01:20:35,841 --> 01:20:37,376
MACAQUES IN LARGER RESERVOIRS.

2315
01:20:37,376 --> 01:20:39,978
SO WE ARE ACTIVELY PURSUING THIS

2316
01:20:39,978 --> 01:20:42,080
THIS YEAR WITH ANIMALS PLACED ON

2317
01:20:42,080 --> 01:20:43,715
ANTIRETROVIRAL THERAPY NOW AT

2318
01:20:43,715 --> 01:20:47,552
WEEK 3 POST INFECTION, AND WHEN

2319
01:20:47,552 --> 01:20:49,521
THEY WERE TREATED WITH THE SAME

2320
01:20:49,521 --> 01:20:50,956
VECTORS GIVEN TO THE 2022

2321
01:20:50,956 --> 01:20:51,423
COHORT.

2322
01:20:51,423 --> 01:20:52,824
AND WE ALSO HAVE THREE ANIMALS

2323
01:20:52,824 --> 01:20:56,795
ENROLLED SO FAR.

2324
01:20:56,795 --> 01:20:57,963
AND AS OF NOW WE HAVE VIRAL

2325
01:20:57,963 --> 01:20:58,864
LOADS, THIS IS STILL VERY

2326
01:20:58,864 --> 01:20:59,731
PRELIMINARY WITH THE CONTROL

2327
01:20:59,731 --> 01:21:01,166
GROUP, ART IS WORKING, IT'S

2328
01:21:01,166 --> 01:21:03,168
SUPPRESSING VIRAL REPLICATION IN

2329
01:21:03,168 --> 01:21:05,103
THE CONTROL, AND EXPERIMENTAL

2330
01:21:05,103 --> 01:21:06,004
ANIMALS, AND WE ALREADY HAVE

2331
01:21:06,004 --> 01:21:07,739
SOME LEVELS OF EXPRESSION THAT

2332
01:21:07,739 --> 01:21:10,809
WE ARE ACTIVELY MONITORING.

2333
01:21:10,809 --> 01:21:13,445
SO JUST TO SUMMARIZE, EARLY ART

2334
01:21:13,445 --> 01:21:16,615
PLUS AAV VECTOR DELIVERY

2335
01:21:16,615 --> 01:21:18,150
PREVENTED OR SUBSTANTIALLY

2336
01:21:18,150 --> 01:21:22,654
DELAYED VIRUS REBOUND IN

2337
01:21:22,654 --> 01:21:24,389
PERINATALLY SHIV INFECTED

2338
01:21:24,389 --> 01:21:27,225
MACAQUES FOLLOWING ATI.

2339
01:21:27,225 --> 01:21:28,894
ANTI-DRUG ANTIBODIES WERE THE

2340
01:21:28,894 --> 01:21:31,430
MAIN FACTOR LIMITING TRANSGENE

2341
01:21:31,430 --> 01:21:34,132
EXPRESSION BUT THEIR IN INCIDENE

2342
01:21:34,132 --> 01:21:36,935
IN INFANTS WAS LOWER THAN THAT

2343
01:21:36,935 --> 01:21:39,237
SEEN IN OLDER MACAQUES.

2344
01:21:39,237 --> 01:21:41,907
THIS IS SHOWING DUE TO NEONATAL

2345
01:21:41,907 --> 01:21:42,607
TOLERANCE.

2346
01:21:42,607 --> 01:21:45,811
AND 10-1074 WAS PRIMARILY

2347
01:21:45,811 --> 01:21:47,546
AFFECTED, IN THE THREE INFANTS

2348
01:21:47,546 --> 01:21:49,648
THAT LOST EXPRESSION DUE TO

2349
01:21:49,648 --> 01:21:50,816
ADAs, SERUM CONCENTRATION OF

2350
01:21:50,816 --> 01:21:53,251
THIS MOLECULE EVENTUALLY

2351
01:21:53,251 --> 01:21:54,786
REBOUNDED CONCOMITANTLY WITH A

2352
01:21:54,786 --> 01:21:57,456
DECLINE IN ADAs, WHICH WE

2353
01:21:57,456 --> 01:21:59,825
RARELY SEE IN JUVENILES OR

2354
01:21:59,825 --> 01:22:00,826
ADULTS.

2355
01:22:00,826 --> 01:22:03,028
SO PLAIN LANGUAGE SUMMARY, THE

2356
01:22:03,028 --> 01:22:04,563
QUESTION WE ASKED WAS, COULD A

2357
01:22:04,563 --> 01:22:08,066
COMBINATION OF EARLY ART PLUS

2358
01:22:08,066 --> 01:22:13,638
AAV THEIR PEE WITH BIOLOGICS

2359
01:22:13,638 --> 01:22:14,873
ENABLE CONTROL -- THIS WORK

2360
01:22:14,873 --> 01:22:16,274
ADVANCES THE FIELD TOWARD A CURE

2361
01:22:16,274 --> 01:22:17,943
BECAUSE IT RAISES THE

2362
01:22:17,943 --> 01:22:19,811
POSSIBILITY THAT DURABLE

2363
01:22:19,811 --> 01:22:21,446
ART-FREE CONTROL OF PERINATAL

2364
01:22:21,446 --> 01:22:22,481
HIV INFECTION CAN BE ACHIEVED

2365
01:22:22,481 --> 01:22:24,082
THROUGH A SINGLE ADMINISTRATION

2366
01:22:24,082 --> 01:22:26,485
OF AAV VECTORS GIVEN

2367
01:22:26,485 --> 01:22:27,018
INTRAMUSCULARLY.

2368
01:22:27,018 --> 01:22:28,887
FOUR INJECTIONS, THAT'S ALL IT

2369
01:22:28,887 --> 01:22:29,888
TOOK FOR THIS STUDY.

2370
01:22:29,888 --> 01:22:31,757
AND WE ARE EXCITED ABOUT THIS

2371
01:22:31,757 --> 01:22:33,825
BECAUSE WITH ADEQUATE

2372
01:22:33,825 --> 01:22:35,827
INVESTMENT, I BELIEVE THAT AAV

2373
01:22:35,827 --> 01:22:41,700
VECTOR DELIVERY OF HIV -- CAN BE

2374
01:22:41,700 --> 01:22:43,902
A KEY TO SUSTAINED -- IN

2375
01:22:43,902 --> 01:22:45,470
CHILDREN IN A WRACT PRACT CAL

2376
01:22:45,470 --> 01:22:46,037
AND SCALABLE WAY.

2377
01:22:46,037 --> 01:22:47,439
SO I WANT TO GIVE THANKS TO THE

2378
01:22:47,439 --> 01:22:50,175
MEMBERS OF MY LAB WHO DID THE

2379
01:22:50,175 --> 01:22:52,077
ASSAYS AND HELPED ME WITH THESE

2380
01:22:52,077 --> 01:22:53,678
EXPERIMENTS, SPECIAL THANKS ALSO

2381
01:22:53,678 --> 01:22:56,148
TO NANCY AND ANN AND MEMBERS OF

2382
01:22:56,148 --> 01:22:58,283
THE TEAM FOR OVERSEEING THE

2383
01:22:58,283 --> 01:22:59,718
PRIMATE STUDIES.

2384
01:22:59,718 --> 01:23:00,152
THANK YOU.

2385
01:23:00,152 --> 01:23:10,328
[APPLAUSE]

2386
01:23:11,196 --> 01:23:12,097
>> HI, EVERYBODY.

2387
01:23:12,097 --> 01:23:13,598
MY NAME IS ANN CHAHROUDI, AND I

2388
01:23:13,598 --> 01:23:14,599
WILL BE TALKING TO YOU ABOUT

2389
01:23:14,599 --> 01:23:16,368
SOME OF THE WORK WE'RE DOING IN

2390
01:23:16,368 --> 01:23:18,136
RF 3 FOR PAVE.

2391
01:23:18,136 --> 01:23:19,771
SO IN RF 3, THE FOCUS IS

2392
01:23:19,771 --> 01:23:21,106
ERADICATION AS YOU ALL KNOW.

2393
01:23:21,106 --> 01:23:25,343
AND WE ARE WORKING TO DEFINE

2394
01:23:25,343 --> 01:23:27,546
PEDIATRIC-SPECIFIC FEATURES OF

2395
01:23:27,546 --> 01:23:29,948
VIRUS PERSISTENCE IN RESERVOIR

2396
01:23:29,948 --> 01:23:31,249
REACTIVATION TO INFORM

2397
01:23:31,249 --> 01:23:33,084
STRATEGIES TO SUCCESSFULLY

2398
01:23:33,084 --> 01:23:34,352
ELIMINATE VIRUS RESERVOIRS.

2399
01:23:34,352 --> 01:23:37,222
AND WE'RE REALLY FOCUSING ON HOW

2400
01:23:37,222 --> 01:23:38,790
WE CAN FACILITATE THE IMMUNE

2401
01:23:38,790 --> 01:23:40,425
SYSTEM AND ENHANCE IMMUNE SYSTEM

2402
01:23:40,425 --> 01:23:43,261
TO CLEAR THOSE RESERVOIRS.

2403
01:23:43,261 --> 01:23:50,735
I LEAD THIS RF WITH PAOLO PALMA.

2404
01:23:50,735 --> 01:23:52,237
THIS IS OUR RF 3 TEAM.

2405
01:23:52,237 --> 01:23:53,905
AND WHAT I'M GOING TO DO FOR THE

2406
01:23:53,905 --> 01:23:56,641
REMAINDER OF THIS TALK IS TO

2407
01:23:56,641 --> 01:23:59,144
PREVIEW A COUPLE OF INFANT

2408
01:23:59,144 --> 01:24:00,545
NON-HUMAN PRIMATE STUDYS THAT WE

2409
01:24:00,545 --> 01:24:02,280
HAVE AND THAT ARE STILL

2410
01:24:02,280 --> 01:24:04,816
HAPPENING THIS YEAR, AND THEN

2411
01:24:04,816 --> 01:24:05,784
TAKE YOU THROUGH A COMPLETED

2412
01:24:05,784 --> 01:24:07,018
STUDY THAT WE STARTED AT THE

2413
01:24:07,018 --> 01:24:11,489
BEGINNING OF THE PAVE PROJECT.

2414
01:24:11,489 --> 01:24:14,359
SO FIRST TO BUILD OFF OF

2415
01:24:14,359 --> 01:24:15,260
MAURICIO'S FANTASTIC RESULTS, WE

2416
01:24:15,260 --> 01:24:17,762
WANTED TO UTILIZE AAV DELIVERY

2417
01:24:17,762 --> 01:24:20,599
OF ECD4IG TO SEE IF WE COULD

2418
01:24:20,599 --> 01:24:21,933
DETERMINE WHETHER THERE WAS AN

2419
01:24:21,933 --> 01:24:23,468
EFFECT ON CLEARANCE OF INFECTED

2420
01:24:23,468 --> 01:24:25,770
CELLS.

2421
01:24:25,770 --> 01:24:29,174
AND SO THIS IS TAKING THE SAME

2422
01:24:29,174 --> 01:24:32,911
APPROACH YET USING AN IGG

2423
01:24:32,911 --> 01:24:34,646
1 VERSION OF ECD4IG AND THE

2424
01:24:34,646 --> 01:24:36,848
REASON FOR THAT IS TO IMPROVE

2425
01:24:36,848 --> 01:24:38,183
ANTIBODY EFFECTOR FUNCTIONS AND

2426
01:24:38,183 --> 01:24:41,353
SO HOPEFULLY HAVE ADCC AND OTHER

2427
01:24:41,353 --> 01:24:42,621
MECHANISMS OF CLEARING INFECTED

2428
01:24:42,621 --> 01:24:43,889
CELLS.

2429
01:24:43,889 --> 01:24:45,891
SO IN THIS STUDY THAT'S

2430
01:24:45,891 --> 01:24:48,827
CURRENTLY ONGOING, WE HAVE 20

2431
01:24:48,827 --> 01:24:50,829
ANIMALS, 10 CONTROLS AND 10

2432
01:24:50,829 --> 01:24:51,696
EXPERIMENTAL ANIMALS.

2433
01:24:51,696 --> 01:24:54,432
THE ANIMALS ARE ALL INFECTED

2434
01:24:54,432 --> 01:24:58,603
WITH SIV MAK251 ORALLY AT

2435
01:24:58,603 --> 01:24:59,704
4 WEEKS OF AGE AND THEN

2436
01:24:59,704 --> 01:25:00,906
ANTIRETROVIRAL THERAPY WAS

2437
01:25:00,906 --> 01:25:01,806
STARTED THREE WEEKS LATER.

2438
01:25:01,806 --> 01:25:02,874
AND AT THE SAME TIME IN THE

2439
01:25:02,874 --> 01:25:05,443
EXPERIMENTAL ANIMALS WHEN THEY

2440
01:25:05,443 --> 01:25:06,311
RECEIVED THE ANTIRETROVIRAL

2441
01:25:06,311 --> 01:25:07,746
THERAPY, THEY ALSO GET AN

2442
01:25:07,746 --> 01:25:12,017
INJECTION OF THE AAV9 ECD 4 IGG

2443
01:25:12,017 --> 01:25:12,150
1.

2444
01:25:12,150 --> 01:25:14,119
WE'RE FOLLOWING THEM THROUGHOUT

2445
01:25:14,119 --> 01:25:17,622
THIS PERIOD OF ART AND THEN WE

2446
01:25:17,622 --> 01:25:18,957
ARE ANTICIPATING THAT IN ORDER

2447
01:25:18,957 --> 01:25:21,559
TO CLEAR THE VIRAL RESERVOIRS OR

2448
01:25:21,559 --> 01:25:22,794
CLEAR THE INFECTED CELLS DURING

2449
01:25:22,794 --> 01:25:25,497
ART, WE WILL NEED A PERIOD OF

2450
01:25:25,497 --> 01:25:26,264
LATENCY REVERSAL.

2451
01:25:26,264 --> 01:25:27,465
SO THIS HAS NOT HAPPENED YET BUT

2452
01:25:27,465 --> 01:25:29,234
THE PLAN IS TO TREAT WITH THE

2453
01:25:29,234 --> 01:25:33,538
SMACK MIMETIC ECD 5582.

2454
01:25:33,538 --> 01:25:34,673
I WILL JUST CALL YOUR ATTENTION

2455
01:25:34,673 --> 01:25:41,413
TO A POSTER FROM A FELLOW IN MY

2456
01:25:41,413 --> 01:25:41,880
LAB.

2457
01:25:41,880 --> 01:25:43,615
HE GOES INTO MUCH GREATER DETAIL

2458
01:25:43,615 --> 01:25:46,017
ON HOW WE SELECTED THESE INFANT

2459
01:25:46,017 --> 01:25:48,119
MACAQUES IN TERMS OF THEIR

2460
01:25:48,119 --> 01:25:50,121
PRE-EXISTING ANTIBODIES TO AAV.

2461
01:25:50,121 --> 01:25:52,324
SO HERE ARE EARLY RESULTS.

2462
01:25:52,324 --> 01:25:55,160
SIMILAR TO WHAT MAURICIO HAS

2463
01:25:55,160 --> 01:25:57,462
SHOWN, WE ARE SEEING EXPRESSION

2464
01:25:57,462 --> 01:26:00,298
OF ECD 4, THE IGG 1 VERSION IN

2465
01:26:00,298 --> 01:26:04,035
ALL OF THESE ANIMALS.

2466
01:26:04,035 --> 01:26:05,370
THESE LAST WE HAVEN'T MEASURED

2467
01:26:05,370 --> 01:26:07,639
YET SO IT'S NOT ABSTINENCE, IT

2468
01:26:07,639 --> 01:26:08,773
JUST HASN'T BEEN MEASURED.

2469
01:26:08,773 --> 01:26:10,742
AND THEN JUST TO REMIND YOU OF

2470
01:26:10,742 --> 01:26:12,043
OUR LATENCY REVERSAL APPROACH,

2471
01:26:12,043 --> 01:26:14,346
SO THIS HAS BEEN TALKED ABOUT IN

2472
01:26:14,346 --> 01:26:15,013
SEVERAL TALKS ALREADY AT THIS

2473
01:26:15,013 --> 01:26:16,448
MEETING SO I WON'T GO INTO

2474
01:26:16,448 --> 01:26:19,718
DETAIL BUT WE'VE PUBLISHED ON IN

2475
01:26:19,718 --> 01:26:28,760
IT ADULTERY ADULT RECE RHESUS ML

2476
01:26:28,760 --> 01:26:29,861
AS -- AND IN PARTICULAR THEY

2477
01:26:29,861 --> 01:26:33,131
HAVE A LOT LESS VIRUS

2478
01:26:33,131 --> 01:26:35,433
REACTIVATION, ARE ON ART

2479
01:26:35,433 --> 01:26:35,767
VIREMIA.

2480
01:26:35,767 --> 01:26:37,335
WE'VE TAKEN THESE RESULTS AND

2481
01:26:37,335 --> 01:26:41,506
WORKED WITH UNC TO PERFORM PK

2482
01:26:41,506 --> 01:26:42,841
MODELING STUDIES TO HELP US

2483
01:26:42,841 --> 01:26:43,608
INFORM THE NEXT DOSE AND WE HAVE

2484
01:26:43,608 --> 01:26:46,244
SOME PILOT STUDIES AS WELL SO WE

2485
01:26:46,244 --> 01:26:47,345
FEEL PREPARED THAT WE SHOULD BE

2486
01:26:47,345 --> 01:26:49,781
ABLE TO ACHIEVE HIGHER LEVELS OF

2487
01:26:49,781 --> 01:26:51,082
LATENCY REVERSAL IN THE INFANTS

2488
01:26:51,082 --> 01:26:53,818
IN THE CURRENT STUDY.

2489
01:26:53,818 --> 01:26:57,188
SO THE NEXT PREYOU HAVE I WILL E

2490
01:26:57,188 --> 01:26:59,324
YOU IS A STUDY FROM THIS GROUP

2491
01:26:59,324 --> 01:27:00,892
LISTED ON THE SCREEN FROM WEILL

2492
01:27:00,892 --> 01:27:02,193
CORNELL MEDICINE WHERE THEY'RE

2493
01:27:02,193 --> 01:27:06,364
WORKING TO INDUCE BNABS, HIV

2494
01:27:06,364 --> 01:27:10,835
ENVELOPE TRIMER I NIGHIZATIO IM.

2495
01:27:10,835 --> 01:27:13,571
THIS IS ACTUALLY A PART OF RF 2,

2496
01:27:13,571 --> 01:27:16,007
BUT I THOUGHT I WOULD PRESENT IT

2497
01:27:16,007 --> 01:27:21,880
TODAY.

2498
01:27:21,880 --> 01:27:25,717
SO THE GOAL OF THESE IS TO

2499
01:27:25,717 --> 01:27:27,218
PRESENT MULTIPLE BNAB EPITOPES

2500
01:27:27,218 --> 01:27:28,686
IN WAYS THAT BEST MIMIC THEIR

2501
01:27:28,686 --> 01:27:30,021
PRESENTATION ON THE NATIVE

2502
01:27:30,021 --> 01:27:31,656
ENVELOPE SPIKE.

2503
01:27:31,656 --> 01:27:36,594
AND THE BG505 SOSIP IS DESCRIBED

2504
01:27:36,594 --> 01:27:39,898
HERE AN THE GT1.1 WHICH ENGAGES

2505
01:27:39,898 --> 01:27:43,968
A BROAD RANGE OF VRC01-CLASS C

2506
01:27:43,968 --> 01:27:45,804
D4 BINDING SITE PRECURSOR BNABS

2507
01:27:45,804 --> 01:27:46,805
IS SHOWN HERE AS WELL.

2508
01:27:46,805 --> 01:27:48,039
SO THIS IS ANOTHER -- THIS IS

2509
01:27:48,039 --> 01:27:49,574
ACTUALLY A STUDY THAT'S BEEN

2510
01:27:49,574 --> 01:27:51,643
COMPLETED BY ASHLEY NELSON, AND

2511
01:27:51,643 --> 01:27:58,183
THIS IS WHERE THEY USE THE BG50L

2512
01:27:58,183 --> 01:28:01,352
AND THE GT1.1 MODIFIED VERSION

2513
01:28:01,352 --> 01:28:03,088
IN INFANT RHESUS MACAQUES THAT

2514
01:28:03,088 --> 01:28:05,056
ARE NAIVE TO SIV SO THIS WAS AS

2515
01:28:05,056 --> 01:28:07,158
PART OF A PROPHYLACTIC VACCINE

2516
01:28:07,158 --> 01:28:07,592
STUDY.

2517
01:28:07,592 --> 01:28:08,893
AND THEY SHOWED THAT IT WAS ABLE

2518
01:28:08,893 --> 01:28:12,230
TO -- THEY WERE ABLE TO INDUCE

2519
01:28:12,230 --> 01:28:15,600
T TIER 1 AND TIER 2 NEUTRALIZING

2520
01:28:15,600 --> 01:28:17,335
ANTIBODIES WITHIN A YEAR OF THIS

2521
01:28:17,335 --> 01:28:19,804
INITIAL PROFILE AND THE

2522
01:28:19,804 --> 01:28:21,106
GT1.1 PRIMED INFANTS DISPLAYED

2523
01:28:21,106 --> 01:28:22,640
SUPERIOR ABILITY TO GENERATE

2524
01:28:22,640 --> 01:28:25,310
PRECURSORS TO CD4 BINDING SITE

2525
01:28:25,310 --> 01:28:26,277
NEUTRALIZING ANTIBODIES, SO YOU

2526
01:28:26,277 --> 01:28:28,780
CAN SEE HERE THE COMPARISON THAT

2527
01:28:28,780 --> 01:28:30,815
THEY MADE WITH INFANT MACAQUES

2528
01:28:30,815 --> 01:28:33,418
AND THE ADULT MACAQUES.

2529
01:28:33,418 --> 01:28:34,886
SO THIS IS THE STUDY THAT WEAR

2530
01:28:34,886 --> 01:28:38,556
DOINGWE'REDOING TAKING THAT APPD

2531
01:28:38,556 --> 01:28:40,558
APPLYING IT IN A THERAPEUTIC

2532
01:28:40,558 --> 01:28:41,092
VACCINE SPACE.

2533
01:28:41,092 --> 01:28:43,695
SO ANIMALS WERE INFECTED WITH

2534
01:28:43,695 --> 01:28:45,830
SHIV SF162P3.

2535
01:28:45,830 --> 01:28:48,133
THIS WAS DONE AT THE OREGON

2536
01:28:48,133 --> 01:28:48,566
PRIMATE CENTER.

2537
01:28:48,566 --> 01:28:50,401
THEY STARTED ANTIRETROVIRAL

2538
01:28:50,401 --> 01:28:51,336
THERAPY ONE WEEK AFTER INFECTION

2539
01:28:51,336 --> 01:28:53,304
AND THIS IS THE SCHEDULE OF

2540
01:28:53,304 --> 01:28:54,172
IMMUNIZATIONS.

2541
01:28:54,172 --> 01:28:56,241
THE SOSIP IMMUNIZATIONS ARE

2542
01:28:56,241 --> 01:29:00,411
BEING GIVEN WITH THE

2543
01:29:00,411 --> 01:29:01,846
TLR7/8 ADJUVANT 3M052.

2544
01:29:01,846 --> 01:29:03,181
SO THE HYPOTHESIS IS THAT

2545
01:29:03,181 --> 01:29:04,482
ADMINISTRATION OF GERMLINE

2546
01:29:04,482 --> 01:29:06,251
TARGETING SOSIP SHORTLY AFTER

2547
01:29:06,251 --> 01:29:08,219
INFECTION WILL LEAD TO

2548
01:29:08,219 --> 01:29:10,855
FOCUSED -- A FOCUSED ANTIBODY

2549
01:29:10,855 --> 01:29:13,825
RESPONSE, DRIVE THE

2550
01:29:13,825 --> 01:29:14,926
EXPANSION/MATURATION OF SPECIFIC

2551
01:29:14,926 --> 01:29:18,763
B CELL CLONAL LINEAGES WITH B

2552
01:29:18,763 --> 01:29:22,066
NABS GENERATED IN VIVO CAPABLE

2553
01:29:22,066 --> 01:29:24,802
OF DELAYING TIME TO REBOUND POST

2554
01:29:24,802 --> 01:29:25,236
ART INTERRUPTION.

2555
01:29:25,236 --> 01:29:26,571
WE'RE USING TWO DIFFERENT

2556
01:29:26,571 --> 01:29:28,339
METHODS, BOTH VECTOR DELIVERY

2557
01:29:28,339 --> 01:29:30,308
AND ACTIVE IMMUNIZATION TO

2558
01:29:30,308 --> 01:29:32,043
ACHIEVE BNAB EXPRESSION IN

2559
01:29:32,043 --> 01:29:33,278
INFANT RHESUS MACAQUES.

2560
01:29:33,278 --> 01:29:37,015
AND WE HAVE SOME ONGOING WORK

2561
01:29:37,015 --> 01:29:38,783
OBVIOUSLY TO DO AS THOSE

2562
01:29:38,783 --> 01:29:39,817
NON-HUMAN PRIMATE STUDIES ARE

2563
01:29:39,817 --> 01:29:40,752
STILL WORKING.

2564
01:29:40,752 --> 01:29:42,420
BUT WHAT IF WE TAKE A STEP BACK

2565
01:29:42,420 --> 01:29:44,722
AND THINK ABOUT PASSIVE

2566
01:29:44,722 --> 01:29:46,024
ADMINISTRATION OF BNABS IN

2567
01:29:46,024 --> 01:29:46,491
INFANTS?

2568
01:29:46,491 --> 01:29:51,663
THAT'S ACTUALLY WHERE WE STAR 

2569
01:29:51,663 --> 01:29:51,896
STARTED.

2570
01:29:51,896 --> 01:29:53,431
SO THIS WORK WHICH WE'RE CALLING

2571
01:29:53,431 --> 01:29:54,532
SURGE AND PURGE AAPPROPRIATE,

2572
01:29:54,532 --> 01:29:58,770
THIS HAS BEEN DISCU --APROA. THD

2573
01:29:58,770 --> 01:30:00,905
AT THE TIME OF OUR INITIATION TO

2574
01:30:00,905 --> 01:30:03,241
ATTEMPT TO IMPEDE OR REDUCE

2575
01:30:03,241 --> 01:30:05,944
RESERVOIR ESTABLISHMENT.

2576
01:30:05,944 --> 01:30:07,912
THIS APPROACH IS PARTICULARLY

2577
01:30:07,912 --> 01:30:12,083
APPEALING FOR INFANTS AND

2578
01:30:12,083 --> 01:30:15,086
CHILDREN BECAUSE FOR MANY OF

2579
01:30:15,086 --> 01:30:16,187
THEM, WE KNOW WHEN THEY WERE

2580
01:30:16,187 --> 01:30:17,822
INFECTED AND WE CAN INTERVENE

2581
01:30:17,822 --> 01:30:18,923
EARLY WITH ANTIRETROVIRAL

2582
01:30:18,923 --> 01:30:22,560
THERAPY PLUS ADDITIONAL

2583
01:30:22,560 --> 01:30:23,861
IMMUNE-BASED INTERVENTIONS.

2584
01:30:23,861 --> 01:30:26,731
SO THE SURGE IS THE USE OF AN

2585
01:30:26,731 --> 01:30:27,398
IMMUNOSTIMULATORY AGENT DURING

2586
01:30:27,398 --> 01:30:29,133
THE PERIOD OF HIGH TURNOVER OF

2587
01:30:29,133 --> 01:30:31,869
INFECTED CELLS SO THIS IS DURING

2588
01:30:31,869 --> 01:30:33,471
ACUTE INFECTION, TO FURTHER

2589
01:30:33,471 --> 01:30:35,740
ENHANCE VIRAL ANTIGEN EXPRESSION

2590
01:30:35,740 --> 01:30:37,842
AS WELL AS PROMOTE T AND NK CELL

2591
01:30:37,842 --> 01:30:38,977
ACTIVATION TO ACCELERATE THE

2592
01:30:38,977 --> 01:30:41,579
CLEARANCE OF INFECTED

2593
01:30:41,579 --> 01:30:41,980
CD4 T-CELLS.

2594
01:30:41,980 --> 01:30:43,248
IN THE STUDY THAT I'LL BE

2595
01:30:43,248 --> 01:30:46,884
DESCRIBING WE USED N-803 AS OUR

2596
01:30:46,884 --> 01:30:49,187
SURGE AGENT.

2597
01:30:49,187 --> 01:30:51,923
THE PURGE IS TO USE PA CIVIL

2598
01:30:51,923 --> 01:30:55,693
ADMINISTERED ENVELOPE-SPECIFIC

2599
01:30:55,693 --> 01:30:56,761
ANTIBODIES THAT WILL WORK IN

2600
01:30:56,761 --> 01:30:58,096
CONCERT WITH INNATE IMMUNE CELLS

2601
01:30:58,096 --> 01:31:00,298
TO CLEAR INFECTED CD4 T-CELLS.

2602
01:31:00,298 --> 01:31:05,536
THE PURGE AGENTS WE USE ARE FOUR

2603
01:31:05,536 --> 01:31:07,438
RHESUS-SPECIFIC MONOCLONAL

2604
01:31:07,438 --> 01:31:11,175
ANTIBODIES DEVELOPED AT THE NIH.

2605
01:31:11,175 --> 01:31:12,377
SO HERE'S THE STUDY DESIGN.

2606
01:31:12,377 --> 01:31:14,879
WE HAD A GROUP THAT JUST HAD ART

2607
01:31:14,879 --> 01:31:19,150
ONLY AS CONTROLS, A GROUP THAT

2608
01:31:19,150 --> 01:31:20,685
RECEIVED MONOCLONAL ANTIBODIES

2609
01:31:20,685 --> 01:31:22,787
AND A GROUP THAT RECEIVED SIV

2610
01:31:22,787 --> 01:31:24,922
ANTIBODIES IN ADDITION TO N-803.

2611
01:31:24,922 --> 01:31:27,625
THEY WERE ALL INFECTED ORALLY,

2612
01:31:27,625 --> 01:31:29,360
STARTED ON ART WITHIN ONE TO TWO

2613
01:31:29,360 --> 01:31:30,328
WEEKS OF THAT INFECTION, AND

2614
01:31:30,328 --> 01:31:33,598
THEN RECEIVED THE ADDITIONAL

2615
01:31:33,598 --> 01:31:34,232
INTERVENTIONS AT THE SAME TIME

2616
01:31:34,232 --> 01:31:36,467
AS ART WAS INITIATED.

2617
01:31:36,467 --> 01:31:37,935
IN THIS STUDY, WE WERE ONLY ABLE

2618
01:31:37,935 --> 01:31:40,972
TO GIVE ONE DOSE OF N-803 DUE TO

2619
01:31:40,972 --> 01:31:44,609
ADVERSE EFFECTS.

2620
01:31:44,609 --> 01:31:45,376
SO WHAT DID WE SEE?

2621
01:31:45,376 --> 01:31:47,378
WE FOUND THAT IN ANIMALS THAT

2622
01:31:47,378 --> 01:31:50,381
RECEIVED N-803, WE SHOWED AN

2623
01:31:50,381 --> 01:31:52,483
INCREASE IN KI67 EXPRESSION ON

2624
01:31:52,483 --> 01:31:54,552
NK CELLS AND CD8 T-CELLS AT DAY

2625
01:31:54,552 --> 01:31:59,624
FOUR, WHICH IS SHOWN HERE.

2626
01:31:59,624 --> 01:32:01,826
CD4 T-CELLS DID NOT HAVE A

2627
01:32:01,826 --> 01:32:03,661
SIMILAR EE CREASE AND THE LEVELS

2628
01:32:03,661 --> 01:32:05,129
DECLINED BY DAY 7 SUCH THAT THEY

2629
01:32:05,129 --> 01:32:05,897
WERE SIMILAR TO THE OTHER

2630
01:32:05,897 --> 01:32:06,564
GROUPS.

2631
01:32:06,564 --> 01:32:07,732
SO THIS WAS PROOF OF CONCEPT

2632
01:32:07,732 --> 01:32:10,968
THAT N-803 WAS DOING WHAT WE

2633
01:32:10,968 --> 01:32:12,603
EXPECTED TO DO IN THESE ANIMALS.

2634
01:32:12,603 --> 01:32:13,871
HOWEVER WE SAW A SIMILAR DECLINE

2635
01:32:13,871 --> 01:32:15,873
OF VIREMIA ON ANTIRETROVIRAL

2636
01:32:15,873 --> 01:32:17,375
THERAPY IN ALL THREE OF THE

2637
01:32:17,375 --> 01:32:18,443
GROUPS, DESPITE THE

2638
01:32:18,443 --> 01:32:19,410
ADMINISTRATION OF THE ANTIBODIES

2639
01:32:19,410 --> 01:32:23,715
AS WELL AS THE N-8 O803, SO

2640
01:32:23,715 --> 01:32:24,615
ALTHOUGH THEY'RE DIFFERENT

2641
01:32:24,615 --> 01:32:25,550
AGENTS AND A DIFFERENT MODEL,

2642
01:32:25,550 --> 01:32:27,051
BUT IT'S DIFFERENT FROM THE

2643
01:32:27,051 --> 01:32:29,821
ECLEAR STUDY THAT MARINA CASKEY

2644
01:32:29,821 --> 01:32:31,155
JUST PRESENTED WHERE THEY SAW A

2645
01:32:31,155 --> 01:32:33,891
FASTER DECLINE IN VIREMIA WITH

2646
01:32:33,891 --> 01:32:35,426
ADMINISTRATION OF ANTIBODIES TO

2647
01:32:35,426 --> 01:32:40,064
ADULTS LIVING WITH HIV.

2648
01:32:40,064 --> 01:32:41,899
WE ALSO DID NOT FIND AN IMPACT

2649
01:32:41,899 --> 01:32:43,768
OF OUR INTERVENTIONS ON THE

2650
01:32:43,768 --> 01:32:46,237
IMPACTED CELLS, SO THIS IS

2651
01:32:46,237 --> 01:32:48,740
LOOKING AT GAG DNA CELLS IN

2652
01:32:48,740 --> 01:32:50,608
PERIPHERAL BLOOD AND LYMPH NODES

2653
01:32:50,608 --> 01:32:51,909
OVER TIME IN ALL GROUPS WHICH

2654
01:32:51,909 --> 01:32:53,811
EVERYTHING LOOKED SIMILAR.

2655
01:32:53,811 --> 01:32:55,580
AND WE ALSO LOOKED AT THE INTACT

2656
01:32:55,580 --> 01:32:58,216
SIV PROVIRAL RESERVOIR IN LYMPH

2657
01:32:58,216 --> 01:32:59,550
NODES, BLOOD AND RECTAL

2658
01:32:59,550 --> 01:33:00,451
BIOPSIES, AND THERE WAS NO

2659
01:33:00,451 --> 01:33:07,992
DIFFERENCE BETWEEN THE GROUPS.

2660
01:33:07,992 --> 01:33:11,562
SIMILARLY TO THESE LAST COUPLE

2661
01:33:11,562 --> 01:33:12,397
OF -- I'LL SHOW YOU WHAT

2662
01:33:12,397 --> 01:33:13,297
HAPPENED AFTER TREATMENT

2663
01:33:13,297 --> 01:33:13,731
INTERRUPTION.

2664
01:33:13,731 --> 01:33:16,467
ALL ANIMALS IN THE GROUPS

2665
01:33:16,467 --> 01:33:18,302
REBOUNDED AT A SIMILAR TIME AND

2666
01:33:18,302 --> 01:33:21,072
WE DID NOT HAVE ANY IMPACT ON

2667
01:33:21,072 --> 01:33:22,640
THE POST REBOUND DYNAMICS IN

2668
01:33:22,640 --> 01:33:25,376
TERMS OF SET POINT.

2669
01:33:25,376 --> 01:33:30,014
SO TO SUMMARIZE THIS STUDY, WE

2670
01:33:30,014 --> 01:33:32,316
SAW SIMILAR PLASMA VIRAL LOAD

2671
01:33:32,316 --> 01:33:33,718
DECAY ACROSS ALL GROUPS, WE DID

2672
01:33:33,718 --> 01:33:37,121
SEE AN INCREASE IN KI67 AT DAY

2673
01:33:37,121 --> 01:33:39,490
FOUR AFTER N-803 ADMINISTRATION,

2674
01:33:39,490 --> 01:33:42,794
AND OVERALL, WE SAW A DECLINE IN

2675
01:33:42,794 --> 01:33:46,964
CD4 T-CELL ASSOCIATED SIV DNA

2676
01:33:46,964 --> 01:33:48,166
INTACT VIRAL DNA OVER TIME IN

2677
01:33:48,166 --> 01:33:50,401
ALL GROUPS BUT WHEN WE LOOKED

2678
01:33:50,401 --> 01:33:51,369
CROSS-SECTIONALLY, THERE WAS NO

2679
01:33:51,369 --> 01:33:52,703
DIFFERENCE.

2680
01:33:52,703 --> 01:33:56,140
AND THEN FINALLY, I WILL JUST

2681
01:33:56,140 --> 01:33:57,542
CALL YOUR ATTENTION TO A POSTER

2682
01:33:57,542 --> 01:34:01,379
THAT'S BEING PRESENTED FROM THE

2683
01:34:01,379 --> 01:34:02,814
ROME GROUP, AND THEY'RE REALLY

2684
01:34:02,814 --> 01:34:04,482
DOING SOME VERY EXCITING STUDIES

2685
01:34:04,482 --> 01:34:07,752
TO DEVELOP A PREDICTIVE PLATFORM

2686
01:34:07,752 --> 01:34:11,155
FOR RESERVOIR REACTIVATION IN

2687
01:34:11,155 --> 01:34:12,290
VIRAL REBOUND THAT WE ARE

2688
01:34:12,290 --> 01:34:16,894
FEEDING DATA FROM THE ATACO

2689
01:34:16,894 --> 01:34:17,995
COHORT DEBBIE DESCRIBED EARLIER

2690
01:34:17,995 --> 01:34:20,331
AS WELL AS THE STUDIES OF SIV IN

2691
01:34:20,331 --> 01:34:22,967
INFANT RHESUS MACAQUES.

2692
01:34:22,967 --> 01:34:24,735
JOHN MARCOUX IS DEVELOPING A

2693
01:34:24,735 --> 01:34:26,204
MATH MACKALL MODEL FOR HELPING

2694
01:34:26,204 --> 01:34:28,706
US PREDICT VIRAL REBOUND IN

2695
01:34:28,706 --> 01:34:30,341
ANIMALS AND IN -- SO THE PLAIN

2696
01:34:30,341 --> 01:34:31,776
LANGUAGE SUMMARY.

2697
01:34:31,776 --> 01:34:33,244
THE KEY QUESTION WE WERE ASKING

2698
01:34:33,244 --> 01:34:35,046
IS CAN THE COMBINATION TREATMENT

2699
01:34:35,046 --> 01:34:40,117
WITH ART, -- IMMUNOSTIMULATORY

2700
01:34:40,117 --> 01:34:42,253
AGENTS RESTRICT RES VOR

2701
01:34:42,253 --> 01:34:44,322
ESTABLISHMENT, CLEAR PERSISTENT

2702
01:34:44,322 --> 01:34:46,390
RESERVOIRS AND/OR DELAY VIRAL

2703
01:34:46,390 --> 01:34:47,158
REBOUND IN INFANTS?

2704
01:34:47,158 --> 01:34:48,893
HOW DOES THIS WORK ADVANCE THE

2705
01:34:48,893 --> 01:34:51,729
FIELD TOWARD CURE OR CONTROL.

2706
01:34:51,729 --> 01:34:54,332
OUR EARLY EXPRESSION DATA FROM

2707
01:34:54,332 --> 01:34:58,002
THE ECD IGG 1 REINFORCES RESULTS

2708
01:34:58,002 --> 01:35:04,609
THAT PLEASTHAT MAURICIO PRESENTE

2709
01:35:04,609 --> 01:35:06,711
DELIVER OUR LATENCY REVERSING

2710
01:35:06,711 --> 01:35:07,545
AGENT.

2711
01:35:07,545 --> 01:35:10,381
THE ACTIVE IMMUNIZATION STRATEGY

2712
01:35:10,381 --> 01:35:12,316
WITH THE SOSIP SHOWS PROMISE FOR

2713
01:35:12,316 --> 01:35:15,052
INDUCTION OF BNAB PRECURSORS IN

2714
01:35:15,052 --> 01:35:17,355
INFANTS FROM THE SIV NAIVE STUDY

2715
01:35:17,355 --> 01:35:18,823
OR SHIV NAIVE STUDY.

2716
01:35:18,823 --> 01:35:22,326
AND THOUGH THE OUTCOMES OF OUR

2717
01:35:22,326 --> 01:35:24,529
SURGE AND PURGE STUDY WERE NOT

2718
01:35:24,529 --> 01:35:25,963
AS HOPED WE GAINED INSIGHT INTO

2719
01:35:25,963 --> 01:35:28,065
THE IMPACT OF COMBINATION

2720
01:35:28,065 --> 01:35:29,066
INTERVENTIONS IN INFANTS.

2721
01:35:29,066 --> 01:35:30,401
SO OVERALL WE THINK THAT THE

2722
01:35:30,401 --> 01:35:31,903
INFANT MONKEY MODEL IS USEFUL TO

2723
01:35:31,903 --> 01:35:34,038
HELP ADVANCE STRATEGIES FOR A

2724
01:35:34,038 --> 01:35:38,209
CURE, AND EQUALLY AS IMPORTANT,

2725
01:35:38,209 --> 01:35:39,410
IT TELLS US WHEN MORE RESEARCH

2726
01:35:39,410 --> 01:35:41,379
IS NEEDED BEFORE WE CONSIDER

2727
01:35:41,379 --> 01:35:42,547
ADVANCING A CERTAIN

2728
01:35:42,547 --> 01:35:43,114
INTERVENTIONAL APPROACH TO

2729
01:35:43,114 --> 01:35:43,714
CHILDREN.

2730
01:35:43,714 --> 01:35:45,149
THESE ARE THE ACKNOWLEDGMENTS

2731
01:35:45,149 --> 01:35:46,851
FOR THE SOSIP STUDIES, AS WELL

2732
01:35:46,851 --> 01:35:50,121
AS THE ACKNOWLEDGMENTS FOR THE

2733
01:35:50,121 --> 01:35:51,422
NON-HUMAN PRIMATE STUDIES WE DID

2734
01:35:51,422 --> 01:35:51,856
AT EMORY.

2735
01:35:51,856 --> 01:35:54,525
NOW I WILL TURN IT OVER TO

2736
01:35:54,525 --> 01:35:55,826
SAVITA TO TALK ABOUT RF 4.

2737
01:35:55,826 --> 01:35:56,193
THANK YOU.

2738
01:35:56,193 --> 01:36:05,803
[APPLAUSE]

2739
01:36:05,803 --> 01:36:07,471
>> GOOD MORNING.

2740
01:36:07,471 --> 01:36:10,975
I'M SAVITA PAHWA FROM THE

2741
01:36:10,975 --> 01:36:11,642
UNIVERSITY OF MIAMI.

2742
01:36:11,642 --> 01:36:13,411
I AM HERE TO INTRODUCE RF 4,

2743
01:36:13,411 --> 01:36:16,914
WHICH IS UNIQUE TO THE PAVE

2744
01:36:16,914 --> 01:36:20,985
COLLABORATORY.

2745
01:36:20,985 --> 01:36:22,286
THE OVERARCHING GOAL IS TO

2746
01:36:22,286 --> 01:36:23,321
OPTIMIZE CUTTING EDGE

2747
01:36:23,321 --> 01:36:24,855
TECHNOLOGIES TO STUDY HIV

2748
01:36:24,855 --> 01:36:26,824
PERSISTENCE IN CHILDREN.

2749
01:36:26,824 --> 01:36:31,629
IT HAS FOUR AIMS, AND ON THE

2750
01:36:31,629 --> 01:36:35,833
LEFT ARE THE -- AIMS 1 AND

2751
01:36:35,833 --> 01:36:37,702
2 DEAL WITH RESERVOIR DYNAMICS

2752
01:36:37,702 --> 01:36:39,337
AND INDUCIBILITY, WHICH WILL BE

2753
01:36:39,337 --> 01:36:40,605
DISCUSSED BY DEBBIE.

2754
01:36:40,605 --> 01:36:43,674
I WILL BE DISCUSSING AIMS 3 AND

2755
01:36:43,674 --> 01:36:47,244
4, AND STARTING WITH IMMUNE

2756
01:36:47,244 --> 01:36:47,612
PROFILING.

2757
01:36:47,612 --> 01:36:50,481
WHICH IS SHARED BETWEEN MIAMI

2758
01:36:50,481 --> 01:36:53,884
AND BOSTON LABS.

2759
01:36:53,884 --> 01:36:56,988
SO THE MAIN QUESTION IN

2760
01:36:56,988 --> 01:36:57,788
IMMUNOLOGIC PROFILING ASK WHAT

2761
01:36:57,788 --> 01:36:59,991
ARE THE IMMUNE RESPONSES AGAINST

2762
01:36:59,991 --> 01:37:03,594
HIV THAT ARE PRESENT, AND/OR ARE

2763
01:37:03,594 --> 01:37:07,665
EFFECTIVE IN THE INFANT IMMUNE

2764
01:37:07,665 --> 01:37:09,433
SYSTEM, BOTH PRE AND POST ART

2765
01:37:09,433 --> 01:37:10,201
INITIATION.

2766
01:37:10,201 --> 01:37:13,738
AND MOST OF THE ASSAYS IN OUR

2767
01:37:13,738 --> 01:37:15,706
TOOLBOX DEAL WITH PHENOTYPIC

2768
01:37:15,706 --> 01:37:17,908
STUDIES UTILIZING MULTIPARAMETER

2769
01:37:17,908 --> 01:37:19,644
FLOW CYTOMETRY AS WELL AS

2770
01:37:19,644 --> 01:37:21,379
FUNCTIONAL STUDIES.

2771
01:37:21,379 --> 01:37:24,315
AND THROUGH RF 4, WE HAVE

2772
01:37:24,315 --> 01:37:26,517
DEVELOPED MULTI-OMIC SINGLE CELL

2773
01:37:26,517 --> 01:37:29,220
ANALYSIS USING SINGLE CELL RNA

2774
01:37:29,220 --> 01:37:30,521
SEQ, AS WELL AS SMALL SCALE

2775
01:37:30,521 --> 01:37:33,691
FUNCTIONAL STUDIES TO DETERMINE

2776
01:37:33,691 --> 01:37:37,094
HOW IMMUNE CELLS REACT TO VIRAL

2777
01:37:37,094 --> 01:37:39,230
INFECTION AND OTHER STIMULI.

2778
01:37:39,230 --> 01:37:41,499
AND HERE ARE SOME OF THE

2779
01:37:41,499 --> 01:37:43,801
HIGHLIGHTS.

2780
01:37:43,801 --> 01:37:47,972
FIRST I WANT TO ACKNOWLEDGE THE

2781
01:37:47,972 --> 01:37:50,541
TARA COHORT WHICH IS A COHORT

2782
01:37:50,541 --> 01:37:53,177
DEVELOPED WITH COLLABORATOR

2783
01:37:53,177 --> 01:37:55,179
MARIA LANE IN MOZAMBIQUE.

2784
01:37:55,179 --> 01:37:57,181
IN INFANTS BORN TO HIV INFECTED

2785
01:37:57,181 --> 01:37:59,917
MOTHERS LEADING TO BIRTH OF HIV

2786
01:37:59,917 --> 01:38:01,686
EXPOSED INFECTED INFANTS, AND

2787
01:38:01,686 --> 01:38:03,220
HIV EXPOSED UNINFECTED

2788
01:38:03,220 --> 01:38:04,321
INASSISTANTS.

2789
01:38:04,321 --> 01:38:09,093
AND WHEN WE DID THE ECCITE-SEQ

2790
01:38:09,093 --> 01:38:11,929
ASSAY, WE FOUND THAT AT ONE

2791
01:38:11,929 --> 01:38:15,199
MONTH POST BIRTH, IN FOUR

2792
01:38:15,199 --> 01:38:16,867
INFANTS THEY EXHIBITED

2793
01:38:16,867 --> 01:38:20,337
ENRICHMENT OF NK AND CD8 T-CELL

2794
01:38:20,337 --> 01:38:23,140
CLUSTERS THAT WERE ABSENT IN

2795
01:38:23,140 --> 01:38:25,176
HEU, AND THOSE ARE SHOWN ON THE

2796
01:38:25,176 --> 01:38:28,879
LEFT ON THESE TWO DIAGRAMS.

2797
01:38:28,879 --> 01:38:30,648
THE RIGHT ONE BEING THE INFECTED

2798
01:38:30,648 --> 01:38:34,185
SHOWING THE CD8 AND THE NK

2799
01:38:34,185 --> 01:38:36,387
CELLS, AND ON THE LEFT ARE THE

2800
01:38:36,387 --> 01:38:39,824
UNINFEBUNINFECTED INFANTS WHO DT

2801
01:38:39,824 --> 01:38:40,491
HAVE THIS.

2802
01:38:40,491 --> 01:38:43,127
THEN ON THE EXTREME RIGHT BO

2803
01:38:43,127 --> 01:38:47,431
DBOTTOM, YOU SEE THE CTL CLONL

2804
01:38:47,431 --> 01:38:49,100
EXPANSION WAS NOT CORRELATED

2805
01:38:49,100 --> 01:38:50,835
WITH VIRAL LOAD.

2806
01:38:50,835 --> 01:38:53,971
SO SOME OF THE HIGHLIGHTS OF THE

2807
01:38:53,971 --> 01:38:56,907
OTHER PART IS THE SMALL SCALE NK

2808
01:38:56,907 --> 01:38:59,110
EFFECTOR CELL FUNCTION ASSAY, IN

2809
01:38:59,110 --> 01:39:03,748
WHICH WE ISOLATED NK CELLS FROM

2810
01:39:03,748 --> 01:39:05,850
3 MILLION PBMC AND CULTURED THEM

2811
01:39:05,850 --> 01:39:10,154
WITH HIV INFECTED CELL LINE HAD

2812
01:39:10,154 --> 01:39:13,657
THE UTT78 AS WELL AS WITH

2813
01:39:13,657 --> 01:39:14,759
UNINFECTED K562.

2814
01:39:14,759 --> 01:39:16,160
WHEN WE DID THE KILLING

2815
01:39:16,160 --> 01:39:18,929
EFFICIENCY OF NK CELLS AT ONE

2816
01:39:18,929 --> 01:39:20,431
MONTH PREART, WE FOUND THAT IT

2817
01:39:20,431 --> 01:39:22,466
WAS REALLY NEGATIVE LIQUOR LATED

2818
01:39:22,466 --> 01:39:28,472
LY CORRELATEDWITH VIRUS LOAD SHE

2819
01:39:28,472 --> 01:39:29,006
EXTREME RIGHT.

2820
01:39:29,006 --> 01:39:30,608
WHEN WE LOOKED AT THE

2821
01:39:30,608 --> 01:39:31,275
TRANSCRIPTIONAL PROGRAMS, WE

2822
01:39:31,275 --> 01:39:34,345
FOUND THAT THE NK CELLS INDUCED

2823
01:39:34,345 --> 01:39:35,146
DIFFERENT TRANSCRIPTIONAL

2824
01:39:35,146 --> 01:39:37,782
PROGRAMS IN RESPONSE TO THE HIV

2825
01:39:37,782 --> 01:39:42,119
INFECTED TARGET CELLS, AND THE

2826
01:39:42,119 --> 01:39:44,555
K562 UNINFECTED CELLS, WHICH ARE

2827
01:39:44,555 --> 01:39:46,590
SHOWN ON THE EXTREME RIGHT ON

2828
01:39:46,590 --> 01:39:47,291
THE BOTTOM.

2829
01:39:47,291 --> 01:39:49,360
SO FOR SUMMARY OF THIS PART, WE

2830
01:39:49,360 --> 01:39:51,495
CAN SAY THAT A COMPREHENSIVE

2831
01:39:51,495 --> 01:39:54,865
IMMUNE ANALYSIS IS POSSIBLE WITH

2832
01:39:54,865 --> 01:39:57,668
VERY FEW CELLS YOU CAN DO FLOW

2833
01:39:57,668 --> 01:39:58,803
CYTOMETRY, SINGLE CELL AND

2834
01:39:58,803 --> 01:39:59,804
EVERYTHING, WITH 5 MILLION

2835
01:39:59,804 --> 01:40:00,004
CELLS.

2836
01:40:00,004 --> 01:40:02,173
IF YOU WANTED TO TAKE A DEEPER

2837
01:40:02,173 --> 01:40:04,408
DIVE, THEN SINGLE CELL RNA SEQ

2838
01:40:04,408 --> 01:40:06,377
WITH EVEN SMALLER SAMPLES ARE

2839
01:40:06,377 --> 01:40:11,115
GOOD FOR SPECIFIC QUESTIONS.

2840
01:40:11,115 --> 01:40:13,517
EXAMPLE, HIGH AND LOW VIRAL

2841
01:40:13,517 --> 01:40:15,920
RESERVOIR AND CLINICAL RESPONSE

2842
01:40:15,920 --> 01:40:16,987
IN CLINICAL TRIALS.

2843
01:40:16,987 --> 01:40:18,422
EMERGING DATA ARE POINTING TO

2844
01:40:18,422 --> 01:40:22,660
EXPANSION OF SUBSETS OF NK AND

2845
01:40:22,660 --> 01:40:25,930
CD8 T-CELLS IN INFANTS WITH HIV

2846
01:40:25,930 --> 01:40:28,065
PRE-ART INFECTION AT ONE TO TWO

2847
01:40:28,065 --> 01:40:29,066
MONTHS OF AGE.

2848
01:40:29,066 --> 01:40:30,167
THE FUTURE DIRECTIONS ARE TO

2849
01:40:30,167 --> 01:40:34,638
DEVELOP THESE MULTI-OMIC RNA SEQ

2850
01:40:34,638 --> 01:40:36,273
ASSAYS AS WELL AS NK EFFECTOR

2851
01:40:36,273 --> 01:40:40,611
FUNCTIONS IN GREATER DEPTH, AND

2852
01:40:40,611 --> 01:40:42,446
TO PERFORM CROSS RF

2853
01:40:42,446 --> 01:40:43,247
COLLABORATIONS WHICH ARE REALLY

2854
01:40:43,247 --> 01:40:45,249
ONGOING WITH THE DIFFERENT

2855
01:40:45,249 --> 01:40:49,620
INVESTIGATORS LISTED HERE.

2856
01:40:49,620 --> 01:40:51,722
THE MAIN PLAYERS IN THE

2857
01:40:51,722 --> 01:40:52,590
UNIVERSITY OF MIAMI TEAM ARE

2858
01:40:52,590 --> 01:40:55,292
SHOWN IN CIRCLES.

2859
01:40:55,292 --> 01:40:58,195
LESLIE WHO'S IN THE AUDIENCE, IN

2860
01:40:58,195 --> 01:41:02,566
THE BACK, IN THE MIDDLE, AND TWO

2861
01:41:02,566 --> 01:41:05,636
GRADUATE STUDENTS, AKSHAY AND

2862
01:41:05,636 --> 01:41:05,836
VINH.

2863
01:41:05,836 --> 01:41:07,271
OF COURSE I HAVE TO BE THANKFUL

2864
01:41:07,271 --> 01:41:09,340
TO OUR COLLABORATORS IN MOAZ AM

2865
01:41:09,340 --> 01:41:18,048
BEAK AMOZAMBIQUE.

2866
01:41:18,048 --> 01:41:19,383
SYSTEM SEROLOGY PIPELINE IS

2867
01:41:19,383 --> 01:41:21,385
FOCUSED ON FINDING CORRELATES

2868
01:41:21,385 --> 01:41:23,487
BETWEEN ANTIBODY BINDING THROUGH

2869
01:41:23,487 --> 01:41:28,492
THE FAB DOMAIN, AS WELL AS TO

2870
01:41:28,492 --> 01:41:29,894
THE ANTIBODY EFFECTOR MEDIATED

2871
01:41:29,894 --> 01:41:31,295
FUNCTIONS WHICH ARE LEVERAGED

2872
01:41:31,295 --> 01:41:33,597
THROUGH THE FC DOMAIN, WHICH ARE

2873
01:41:33,597 --> 01:41:35,733
SHOWN IN THE BOTTOM BOX WITH ALL

2874
01:41:35,733 --> 01:41:38,035
THE DIFFERENT FUNCTIONS.

2875
01:41:38,035 --> 01:41:40,771
AND ON THE RIGHT SIDE IS THE

2876
01:41:40,771 --> 01:41:42,172
HEAT MAP SHOWING THAT YOU COULD

2877
01:41:42,172 --> 01:41:46,043
REALLY PROFILE THIS RESPONSE.

2878
01:41:46,043 --> 01:41:47,811
WE HAVE FOUR ORDERS OF MAGNITUDE

2879
01:41:47,811 --> 01:41:50,114
OF LINEAR RANGE OF DETECTION.

2880
01:41:50,114 --> 01:41:53,450
AND THESE ASSAYS ARE PERFORMED

2881
01:41:53,450 --> 01:41:59,356
IN BOSTON, IN THE LAB AT THE

2882
01:41:59,356 --> 01:41:59,890
INSTITUTE.

2883
01:41:59,890 --> 01:42:01,659
HERE THIS IS SHOWING THAT IN A

2884
01:42:01,659 --> 01:42:03,727
STUDY THAT WAS PERFORMED WITH

2885
01:42:03,727 --> 01:42:08,866
VACCINE RECIPIENTS OF HIV, OVER

2886
01:42:08,866 --> 01:42:11,235
A 72-MONTH PERIOD, THAT THE IGG

2887
01:42:11,235 --> 01:42:13,737
1 AND IGG 3 WERE POSITIVELY AND

2888
01:42:13,737 --> 01:42:15,406
INVERSE LIQUOR LATED

2889
01:42:15,406 --> 01:42:17,875
RESPECTIVELY WITH THE LATENT HIV

2890
01:42:17,875 --> 01:42:18,842
RESERVOIR SIZE.

2891
01:42:18,842 --> 01:42:22,579
AND HERE IS THE MODEL, SHOWING

2892
01:42:22,579 --> 01:42:25,950
ON THE TOP THAT THE IGG

2893
01:42:25,950 --> 01:42:28,953
3 RESPONSES ARE NEGATIVELY

2894
01:42:28,953 --> 01:42:31,789
CORRELATED, WHEREAS THE IGG

2895
01:42:31,789 --> 01:42:32,890
1 RESPONSES ARE POSITIVELY

2896
01:42:32,890 --> 01:42:34,291
CORRELATED WITH THE LATENT

2897
01:42:34,291 --> 01:42:35,259
RESERVOIR.

2898
01:42:35,259 --> 01:42:42,433
AND THIS IS THE TEAM OF RHINE RN

2899
01:42:42,433 --> 01:42:42,766
MCNAMERA.

2900
01:42:42,766 --> 01:42:44,501
THE QUESTION IS WHAT IS THE ROLE

2901
01:42:44,501 --> 01:42:46,704
OF ANTIVIRAL IMMUNITY IN VIRUS

2902
01:42:46,704 --> 01:42:48,539
CONTROL AND RESERVOIR DECAY IN

2903
01:42:48,539 --> 01:42:50,274
PRE-ART AND ART-TREATED

2904
01:42:50,274 --> 01:42:51,475
CHILDREN.

2905
01:42:51,475 --> 01:42:54,211
AND I THINK SOME OF THESE

2906
01:42:54,211 --> 01:42:57,348
TECHNOLOGIES WHICH WILL MINIMIZE

2907
01:42:57,348 --> 01:43:00,184
INPUT WILL HELP DRIVE EFFECTOR

2908
01:43:00,184 --> 01:43:01,385
MECHANISMS AGAINST HIV AND THE

2909
01:43:01,385 --> 01:43:03,954
SYSTEM SEROLOGY IS EXPLORING NEW

2910
01:43:03,954 --> 01:43:06,256
TOOLS TO ANALYZE RESERVOIRS.

2911
01:43:06,256 --> 01:43:08,125
AND THESE ARE ENCOURAGING

2912
01:43:08,125 --> 01:43:09,760
STUDIES BECAUSE THEY COULD

2913
01:43:09,760 --> 01:43:11,128
OVERCOME LIMITED BLOOD SAMPLING

2914
01:43:11,128 --> 01:43:14,531
IN PEDIATRIC POPULATIONS, AND,

2915
01:43:14,531 --> 01:43:16,066
THEREFORE, MOVE THE CURE FIELD

2916
01:43:16,066 --> 01:43:16,300
FORWARD.

2917
01:43:16,300 --> 01:43:21,805
YOAND THE FINAL AIM WAS AIM FOU,

2918
01:43:21,805 --> 01:43:25,709
WHICH IS IMMUNOPET IMAGING IN

2919
01:43:25,709 --> 01:43:28,078
NON-HUMAN PRIMATES FOR

2920
01:43:28,078 --> 01:43:31,148
VISUALIZING VIRAL RESERVOIRS.

2921
01:43:31,148 --> 01:43:36,253
USING ZIRCONIUM LABELED ANTIBODY

2922
01:43:36,253 --> 01:43:37,454
VRC07, YOU SEE PICTURES OF THESE

2923
01:43:37,454 --> 01:43:38,922
TWO ANIMALS TWO WEEKS POST

2924
01:43:38,922 --> 01:43:40,791
INFECTION AND 10 WEEKS POST ART,

2925
01:43:40,791 --> 01:43:44,094
AND YOU CAN SEE THESE

2926
01:43:44,094 --> 01:43:45,929
RESERVOIRS, THESE SITES OF VIRAL

2927
01:43:45,929 --> 01:43:47,698
REPLICATION REALLY LIGHT UP,

2928
01:43:47,698 --> 01:43:49,500
WHICH ARE MUCH GREATER IN THE

2929
01:43:49,500 --> 01:43:54,304
EARLY PHASE, AND MUCH SMALLER

2930
01:43:54,304 --> 01:43:58,208
AFTER ARV INSTITUTION AFTER 10

2931
01:43:58,208 --> 01:43:58,575
WEEKS.

2932
01:43:58,575 --> 01:44:02,346
SO THE SUMMARY IS THAT CAN WE

2933
01:44:02,346 --> 01:44:04,214
OPTIMIZE PRE-CLINICAL PET

2934
01:44:04,214 --> 01:44:06,950
IMAGING, AND YES, AND CAN THIS

2935
01:44:06,950 --> 01:44:08,986
BECOME COMPLEMENTARY TO

2936
01:44:08,986 --> 01:44:10,421
QUANTITATIVE ASSAYS TO ASSESS

2937
01:44:10,421 --> 01:44:11,522
VIRAL INFECTION?

2938
01:44:11,522 --> 01:44:14,258
AND FINALLY, THESE COULD REALLY

2939
01:44:14,258 --> 01:44:18,128
BE POSSIBLY OVERCOME INVASIVE

2940
01:44:18,128 --> 01:44:19,430
PROCEDURES SUCH AS BIOPSIES THAT

2941
01:44:19,430 --> 01:44:24,034
ARE NEEDED TO DETECT AND LOCATE

2942
01:44:24,034 --> 01:44:26,737
HIV REPLICATION IN TISSUES.

2943
01:44:26,737 --> 01:44:28,605
NOW I HAPPENED IT OVER TO DEB.

2944
01:44:28,605 --> 01:44:31,108
>> THANKS, SAVITA.

2945
01:44:31,108 --> 01:44:32,409
IN THE INTEREST OF TIME I'M

2946
01:44:32,409 --> 01:44:33,811
ACTUALLY GOING TO SKIP THE

2947
01:44:33,811 --> 01:44:34,678
RESERVOIR COMPONENT AND HAND IT

2948
01:44:34,678 --> 01:44:36,980
OVER TO JESSICA.

2949
01:44:36,980 --> 01:44:38,782
BUT JUST TO MAKE ONE POINT IN

2950
01:44:38,782 --> 01:44:40,984
TERMS OF THE THEME OF SEX

2951
01:44:40,984 --> 01:44:42,419
DIFFERENCES IN HIV RESERVOIR

2952
01:44:42,419 --> 01:44:45,289
SIZE, WE JUST COMPLETED A STUDY

2953
01:44:45,289 --> 01:44:47,724
IN A U.S. COHORT USING THE IPDA

2954
01:44:47,724 --> 01:44:50,160
ASSAY THAT WAS DESCRIBED IN THE

2955
01:44:50,160 --> 01:44:51,528
WELL MATCHED COHORT, THIS WORK

2956
01:44:51,528 --> 01:44:54,131
WAS DONE WHEN SHE WAS A MASTER'S

2957
01:44:54,131 --> 01:44:56,767
STUDENT IN MY LAB IN

2958
01:44:56,767 --> 01:45:02,406
COLLABORATION WITH A PEDIATRIC

2959
01:45:02,406 --> 01:45:03,740
FAK SCORE STUDY.

2960
01:45:03,740 --> 01:45:05,476
TIME OF VIROLOGIC SUPPRESSION IN

2961
01:45:05,476 --> 01:45:06,910
EARLY INFANCY OR CHILDHOOD

2962
01:45:06,910 --> 01:45:08,612
AROUND 14 MONTHS OF AGE, IN

2963
01:45:08,612 --> 01:45:11,148
ORANGE ARE THE GIRLS, SEX

2964
01:45:11,148 --> 01:45:12,583
ASSIGNED AT BIRTH AND IN PURPLE,

2965
01:45:12,583 --> 01:45:14,618
THE BOYS, AND IN THE LATE

2966
01:45:14,618 --> 01:45:17,020
SUPPRESSED GROUP, YOU CAN SEE

2967
01:45:17,020 --> 01:45:18,422
TOTAL HIV DNA IS ACTUALLY

2968
01:45:18,422 --> 01:45:19,189
INCREASING IN THE GIRLS.

2969
01:45:19,189 --> 01:45:22,326
IT HIGHER IN GIRLS VERSUS BOYS

2970
01:45:22,326 --> 01:45:29,766
AND EVEN DEFECTIVE HAVE A

2971
01:45:29,766 --> 01:45:30,968
DIFFERENT -- AND AGE OF

2972
01:45:30,968 --> 01:45:31,935
VIROLOGIC SUPPRESSION REALLY

2973
01:45:31,935 --> 01:45:33,036
MATTERS.

2974
01:45:33,036 --> 01:45:34,104
SUPPORTING ACTUALLY DEVELOPMENT

2975
01:45:34,104 --> 01:45:36,974
OF THE IPD ASSAY FOR APPLICATION

2976
01:45:36,974 --> 01:45:39,676
OF CROSS PEDIATRIC STUDIES.

2977
01:45:39,676 --> 01:45:41,411
THERE'S A POSTER IN TERMS OF

2978
01:45:41,411 --> 01:45:43,947
PROVIRAL LANDSCAPE ANALYSIS

2979
01:45:43,947 --> 01:45:45,649
OF -- INFECTIONS JUST SHOWING

2980
01:45:45,649 --> 01:45:47,117
HIGH BURDEN OF INTACT PRO

2981
01:45:47,117 --> 01:45:48,485
VIRUSES SO WE BELIEVE THESE ARE

2982
01:45:48,485 --> 01:45:50,220
ACTUALLY DEPLETED OVER TIME

2983
01:45:50,220 --> 01:45:51,188
PERHAPS BY SOME OF THE

2984
01:45:51,188 --> 01:45:52,723
MECHANISMS THAT SAVITA HAS

2985
01:45:52,723 --> 01:45:53,157
DESCRIBED.

2986
01:45:53,157 --> 01:45:54,258
SO I'M GOING TO TURN IT OVER.

2987
01:45:54,258 --> 01:45:56,326
I WANT TO THANK EVERYONE ON THE

2988
01:45:56,326 --> 01:45:57,628
TEAMS AND TURN IT OVER TO

2989
01:45:57,628 --> 01:46:04,401
JESSICA FOR THE COMMUNITY.

2990
01:46:04,401 --> 01:46:06,236
>> SO WE SEE THERE'S A LOT
OF

2991
01:46:06,236 --> 01:46:07,204
REALLY GREAT SCIENCE AND IT'S

2992
01:46:07,204 --> 01:46:08,305
HARD TO CONDENSE THAT DOWN AND

2993
01:46:08,305 --> 01:46:09,339
THAT IS ONE OF THE THINGS THAT

2994
01:46:09,339 --> 01:46:12,543
THE COMMUNITY IS -- WHAT WE'RE

2995
01:46:12,543 --> 01:46:13,610
TRY TO REALLY LEAD IN THIS

2996
01:46:13,610 --> 01:46:14,178
PROGRAM.

2997
01:46:14,178 --> 01:46:15,379
SO DEBBIE ALREADY OUTLINED THAT

2998
01:46:15,379 --> 01:46:18,515
WE DO HAVE FOUR CORE PARTNERS AS

2999
01:46:18,515 --> 01:46:21,585
PART OF THE PAVE NETWORK.

3000
01:46:21,585 --> 01:46:22,886
SO JUST TO SAY WE DO HAVE A

3001
01:46:22,886 --> 01:46:23,554
COMMUNITY ADVISORY BOARD.

3002
01:46:23,554 --> 01:46:24,955
IT IS A GLOBAL ADVISORY BOARD,

3003
01:46:24,955 --> 01:46:27,257
WE DO HAVE A NUMBER OF COUNTRIES

3004
01:46:27,257 --> 01:46:27,558
REPRESENTED.

3005
01:46:27,558 --> 01:46:29,226
I DO WANT TO HIGHLIGHT MAYBE TWO

3006
01:46:29,226 --> 01:46:32,029
SPECIFIC PROJECTS, SO WORKING ON

3007
01:46:32,029 --> 01:46:34,965
A PERCEPTIONS PROJECT, ONE IS

3008
01:46:34,965 --> 01:46:42,673
LED BY TWO CORE MEMBERS FROM

3009
01:46:42,673 --> 01:46:46,210
NIGERIA AND UGANDA, AND THIS HER

3010
01:46:46,210 --> 01:46:49,179
CAMPAIGN OR WOMEN FOR HIV CURE

3011
01:46:49,179 --> 01:46:49,880
REALLY FEATURES YOUNG WOMEN

3012
01:46:49,880 --> 01:46:51,281
LIVING WITH PERINATAL HIV

3013
01:46:51,281 --> 01:46:52,616
TALKING ABOUT THEIR STORY AND

3014
01:46:52,616 --> 01:46:54,651
WHAT HIV CURE MEANS AND I'VE

3015
01:46:54,651 --> 01:46:55,319
SHOWN TWO TILES HERE.

3016
01:46:55,319 --> 01:46:57,054
WE'RE BEGINNING TO EXPAND THAT

3017
01:46:57,054 --> 01:46:58,522
OUT AND WE'LL BE CREATING A

3018
01:46:58,522 --> 01:46:59,223
VIDEO OUT OF THAT.

3019
01:46:59,223 --> 01:47:00,791
AND I ALSO WANT TO HIGHLIGHT

3020
01:47:00,791 --> 01:47:02,826
THAT WE'RE NOT JUST FOCUSING ON

3021
01:47:02,826 --> 01:47:04,995
THE ENGAGEMENT AND LITERACY

3022
01:47:04,995 --> 01:47:06,296
ELEMENT BUT ALSO AROUND THE

3023
01:47:06,296 --> 01:47:07,397
ENABLING ENVIRONMENT, SO WE

3024
01:47:07,397 --> 01:47:11,702
ACTUALLY HAVE HERE OUR CAB CHAIR

3025
01:47:11,702 --> 01:47:13,737
SPEAKING WITH THE UGANDA

3026
01:47:13,737 --> 01:47:15,038
NATIONAL SCIENCE AND TECHNOLOGY

3027
01:47:15,038 --> 01:47:16,340
COUNCIL ON PEDIATRIC HIV CURE

3028
01:47:16,340 --> 01:47:16,673
RESEARCH.

3029
01:47:16,673 --> 01:47:17,908
WE HAVE DONE AGAIN, THINKING

3030
01:47:17,908 --> 01:47:19,843
ABOUT THE METRICS, WE DID THE

3031
01:47:19,843 --> 01:47:21,378
SURVEY THROUGH THIS SOUTH

3032
01:47:21,378 --> 01:47:22,379
AFRICAN HIV CLINICIAN SOCIETY

3033
01:47:22,379 --> 01:47:23,647
AROUND WHAT THEIR KNOWLEDGE

3034
01:47:23,647 --> 01:47:25,182
LEVEL IS, AND WE'RE PLANNING ON

3035
01:47:25,182 --> 01:47:26,383
REPEATING THIS SURVEY TO AGAIN

3036
01:47:26,383 --> 01:47:28,151
THINK ABOUT HOW OUR PROGRAM AND

3037
01:47:28,151 --> 01:47:30,487
THE WEBINARS AND IN-PERSON

3038
01:47:30,487 --> 01:47:31,588
PROGRAMS THAT WE'VE DONE HAS

3039
01:47:31,588 --> 01:47:32,589
REALLY EXPANDED THAT KNOWLEDGE

3040
01:47:32,589 --> 01:47:34,591
OVER TIME.

3041
01:47:34,591 --> 01:47:35,892
WE'RE AGAIN THINKING ABOUT THIS

3042
01:47:35,892 --> 01:47:36,360
ENABLING ENVIRONMENT.

3043
01:47:36,360 --> 01:47:37,628
IT'S NOT ENOUGH TO JUST THINK

3044
01:47:37,628 --> 01:47:40,530
ABOUT LITERACY, WE ALSO REALLY

3045
01:47:40,530 --> 01:47:47,804
FOCUS ON BUILDING THE ADD SEW VY

3046
01:47:47,804 --> 01:47:54,678
SO INVEST BEING IN THE COMMUNI 

3047
01:47:54,678 --> 01:47:55,612
TO GROW THE SCIENCE IN THE

3048
01:47:55,612 --> 01:47:55,946
REGION.

3049
01:47:55,946 --> 01:47:58,682
WE HAVE TWO HERE FOCUSING ON THE

3050
01:47:58,682 --> 01:47:59,549
CONGRESSIONAL DELEGATION HERE SO

3051
01:47:59,549 --> 01:48:01,718
WE'VE DONE TWO CONGRESSIONAL

3052
01:48:01,718 --> 01:48:03,153
LUNCHES AS WELL AS OUTREACH TO

3053
01:48:03,153 --> 01:48:03,920
THE FDA.

3054
01:48:03,920 --> 01:48:05,989
WE ALSO AGAIN HAVE A COMMUNITY

3055
01:48:05,989 --> 01:48:07,224
PERCEPTIONS PARTNERSHIP AND THIS

3056
01:48:07,224 --> 01:48:08,892
IS REALLY LEVERAGING A CROSS

3057
01:48:08,892 --> 01:48:09,793
COLLABORATORY PARTNERSHIP, BUT

3058
01:48:09,793 --> 01:48:12,029
I'VE JUST FOCUSED HERE ON SOME

3059
01:48:12,029 --> 01:48:13,563
OF THE PEDIATRIC AND ADOLESCENT

3060
01:48:13,563 --> 01:48:14,464
CONCERNS OF WHAT IT MEANS TO

3061
01:48:14,464 --> 01:48:15,799
CONTROL THE VIRUS AND NOT JUST

3062
01:48:15,799 --> 01:48:17,668
THINKING ABOUT ERADICATION, BUT

3063
01:48:17,668 --> 01:48:19,236
THINGS AS SIMPLE AS YOU KNOW,

3064
01:48:19,236 --> 01:48:21,104
WHO GETS TO DECIDE WHETHER I GO

3065
01:48:21,104 --> 01:48:22,372
BACK ON THERAPY, IS IT MYSELF OR

3066
01:48:22,372 --> 01:48:25,008
IS IT MY PARENTS.

3067
01:48:25,008 --> 01:48:27,377
AGAIN WE'RE ALSO THINKING ABOUT

3068
01:48:27,377 --> 01:48:29,680
THE SOCIAL SCIENCE AS PEACT, SO

3069
01:48:29,680 --> 01:48:30,714
PARTNERING TO THINK ABOUT AN

3070
01:48:30,714 --> 01:48:32,049
ETHICS PAPER THAT EXPANDS ON

3071
01:48:32,049 --> 01:48:33,183
SOME OF THE WORK THAT SHE HAS

3072
01:48:33,183 --> 01:48:34,318
DONE AND OTHERS IN THE COMMUNITY

3073
01:48:34,318 --> 01:48:35,585
ON SETTING THE RESEARCH AGENDA.

3074
01:48:35,585 --> 01:48:36,453
AND THEN SOME OF THE THINGS THAT

3075
01:48:36,453 --> 01:48:39,690
WE'RE REALLY LOOKING FORWARD TO

3076
01:48:39,690 --> 01:48:40,791
IS AGAIN THIS COMMUNITY VOICES

3077
01:48:40,791 --> 01:48:41,925
CAMPAIGN PARTNERING WITH

3078
01:48:41,925 --> 01:48:43,327
DIFFERENT GROUPS AND YOU'LL SEE

3079
01:48:43,327 --> 01:48:45,796
US POPPING UP AT SOME VARIOUS

3080
01:48:45,796 --> 01:48:46,330
CONFERENCES IN THE REGION.

3081
01:48:46,330 --> 01:48:49,333
THANK YOU.

3082
01:48:49,333 --> 01:48:52,703
[APPLAUSE]

3083
01:48:52,703 --> 01:48:54,871
>> THANK YOU, TO EVERYONE.

3084
01:48:54,871 --> 01:48:55,939
SPEAKERS, WE HAVE THE TIME FOR

3085
01:48:55,939 --> 01:48:57,641
ONE OR TWO QUESTIONS, SO IF YOU

3086
01:48:57,641 --> 01:48:58,675
HAVE ANY QUESTIONS, PLEASE COME

3087
01:48:58,675 --> 01:49:02,212
TO THE MIC.

3088
01:49:02,212 --> 01:49:02,846
>> HI.

3089
01:49:02,846 --> 01:49:04,715
I HAD A QUESTION TO DR. MARTINS.

3090
01:49:04,715 --> 01:49:06,550
FIRST OF ALL, AMAZING DATA, VERY

3091
01:49:06,550 --> 01:49:07,617
IMPRESSIVE.

3092
01:49:07,617 --> 01:49:11,621
I GUESS MY QUESTION RELATES TO

3093
01:49:11,621 --> 01:49:11,888
101074.

3094
01:49:11,888 --> 01:49:12,856
WOULD YOU SAY THAT IT'S DOING

3095
01:49:12,856 --> 01:49:15,492
MOST OF THE HEAVY LIFTING, SINCE

3096
01:49:15,492 --> 01:49:18,762
ONCE LEVELS DROPPED, ECD

3097
01:49:18,762 --> 01:49:21,164
4 ITSELF WAS ENABLED TO CONTROL

3098
01:49:21,164 --> 01:49:21,398
VIREMIA?

3099
01:49:21,398 --> 01:49:23,967
AND I GUESS THE SECOND QUESTION

3100
01:49:23,967 --> 01:49:27,571
WOULD BE WHETHER YOU HAVE ANY

3101
01:49:27,571 --> 01:49:28,939
EXPLANATION WHY TRANSGENE

3102
01:49:28,939 --> 01:49:30,540
EXPRESSION DROPPED AND THEN CAME

3103
01:49:30,540 --> 01:49:31,174
BACK UP LATER?

3104
01:49:31,174 --> 01:49:32,309
I THOUGHT THAT WAS REALLY

3105
01:49:32,309 --> 01:49:33,543
INTERESTING ON THOSE TWO

3106
01:49:33,543 --> 01:49:35,479
DIFFERENT MACAQUES.

3107
01:49:35,479 --> 01:49:36,646
>> THANK YOU.

3108
01:49:36,646 --> 01:49:38,248
VERY GOOD QUESTION.

3109
01:49:38,248 --> 01:49:42,619
SO YEAH, 101074 WAS DEFINITELY

3110
01:49:42,619 --> 01:49:44,488
REQUIRED FOR THE MAINTENANCE OF

3111
01:49:44,488 --> 01:49:46,223
VIROLOGIC CONTROL.

3112
01:49:46,223 --> 01:49:47,758
BUT WE DON'T KNOW IF IT WAS

3113
01:49:47,758 --> 01:49:49,292
SUFFICIENT BECAUSE IN ALL CASES,

3114
01:49:49,292 --> 01:49:51,661
THE EXPERIMENTAL ANIMALS HAD

3115
01:49:51,661 --> 01:49:56,800
PERSISTENT EXPRESSION OF ECD

3116
01:49:56,800 --> 01:49:57,100
4IG.

3117
01:49:57,100 --> 01:49:58,702
 -- IF THEY HAD 1074 ONLY

3118
01:49:58,702 --> 01:49:59,836
BECAUSE AGAIN WE DIDN'T HAVE ANY

3119
01:49:59,836 --> 01:50:02,873
EXAMPLES OF ANIMALS WITHIN

3120
01:50:02,873 --> 01:50:04,741
10-1074 ONLY BUT NO ECD 4G.

3121
01:50:04,741 --> 01:50:06,910
BUT I THINK MY IMPRESSION IS WE

3122
01:50:06,910 --> 01:50:08,645
WILL NEED COMBINATION OF HIV

3123
01:50:08,645 --> 01:50:10,180
BIOLOGICS FOR MAINTAINING

3124
01:50:10,180 --> 01:50:11,047
STRINGENT CONTROL AND THAT'S

3125
01:50:11,047 --> 01:50:12,282
WHAT WE SHOULD BE PURSUING IN

3126
01:50:12,282 --> 01:50:12,816
THE FUTURE.

3127
01:50:12,816 --> 01:50:18,588
YOUR QUESTION ABOUT WHY ADAs

3128
01:50:18,588 --> 01:50:20,657
WANED IN THE INFANTS AND THEN

3129
01:50:20,657 --> 01:50:21,091
EXPRESSION RECURRED.

3130
01:50:21,091 --> 01:50:22,526
I DON'T KNOW THE ANSWER TO THAT.

3131
01:50:22,526 --> 01:50:23,960
I'M VERY INTERESTED IN STUDYING

3132
01:50:23,960 --> 01:50:24,494
THAT PHENOMENON.

3133
01:50:24,494 --> 01:50:25,929
IT SEEMS TO BE SOMETHING UNIQUE

3134
01:50:25,929 --> 01:50:28,999
TO INFANTS.

3135
01:50:28,999 --> 01:50:30,934
WE HAVE A MAJOR RESEARCH PROGRAM

3136
01:50:30,934 --> 01:50:33,570
IN MY LAB TRYING TO UNDERSTAND

3137
01:50:33,570 --> 01:50:35,305
MECHANISMS FOR EARLY LIFE

3138
01:50:35,305 --> 01:50:36,039
TOLERANCE AND I THINK IT HAS TO

3139
01:50:36,039 --> 01:50:39,409
DO WITH THAT.

3140
01:50:39,409 --> 01:50:39,910
>> THANK YOU.

3141
01:50:39,910 --> 01:50:42,879
>> SO I HAVE A QUESTION
FOR

3142
01:50:42,879 --> 01:50:53,390
DEBBIE ABOUT STUDY ABOUT THE --

3143
01:50:53,390 --> 01:50:59,729
HOW MANY -- YOU DID?

3144
01:50:59,729 --> 01:51:01,264
>> I'M SORRY, I COULDN'T
HEAR

3145
01:51:01,264 --> 01:51:02,499
YOUR QUESTION.

3146
01:51:02,499 --> 01:51:07,804
>> SO YOU MENTIONED YOU
SEE THE

3147
01:51:07,804 --> 01:51:12,042
CNS -- HOW MANY DONORS YOU DID

3148
01:51:12,042 --> 01:51:12,709
FOR THAT?

3149
01:51:12,709 --> 01:51:16,146
IS IT DOMINANT OR JUST VERY FEW

3150
01:51:16,146 --> 01:51:16,346
CASE?

3151
01:51:16,346 --> 01:51:18,582
>> SO I ACTUALLY DIDN'T
SHOW THE

3152
01:51:18,582 --> 01:51:20,650
ACTUAL DATA BECAUSE THIS WORK

3153
01:51:20,650 --> 01:51:23,353
WAS DONE IN CATHERINE'S GROUP

3154
01:51:23,353 --> 01:51:24,354
AND I KNOW IT WOULD GENERATE A

3155
01:51:24,354 --> 01:51:28,391
LOT OF QUESTIONS.

3156
01:51:28,391 --> 01:51:30,026
ESSENTIALLY WHAT SHE'S FOUND,

3157
01:51:30,026 --> 01:51:32,329
AND SHE'S NOT HERE TO ADDRESS

3158
01:51:32,329 --> 01:51:33,497
THE QUESTIONS WHICH IS WHY I

3159
01:51:33,497 --> 01:51:34,798
DIDN'T GO INTO DETAILS.

3160
01:51:34,798 --> 01:51:37,200
THE REALLY -- THE MAIN AIM RIGHT

3161
01:51:37,200 --> 01:51:38,869
NOW IS TO ESTABLISH

3162
01:51:38,869 --> 01:51:42,439
METHODOLOGIES TO REPRODUCIBLY DO

3163
01:51:42,439 --> 01:51:44,641
THE CAPTURE ASSAY AND ALSO THE

3164
01:51:44,641 --> 01:51:46,276
PSEUDOVIRUS NEUTRALIZATION AND

3165
01:51:46,276 --> 01:51:46,943
INFECTION ASSAYS, AND SO THE

3166
01:51:46,943 --> 01:51:48,979
PROOF OF CONCEPT IN A CHILD WITH

3167
01:51:48,979 --> 01:51:51,281
NO DETECTABLE PERIPHERAL BLOOD

3168
01:51:51,281 --> 01:51:53,650
RESERVOIR WHO THEN REBOUNDED,

3169
01:51:53,650 --> 01:51:59,256
SHE IDENTIFIED -- TROPIC IN

3170
01:51:59,256 --> 01:51:59,589
THOSE.

3171
01:51:59,589 --> 01:52:01,992
BUT I REALLY CAN'T ANSWER MORE

3172
01:52:01,992 --> 01:52:02,759
SPECIFIC ON IT.

3173
01:52:02,759 --> 01:52:04,494
>> I'M EXTREMELY
INTERESTED ON

3174
01:52:04,494 --> 01:52:08,298
THAT BECAUSE WE DID -- WE DID

3175
01:52:08,298 --> 01:52:10,600
THE ANIMALS -- DIFFERENCE AND

3176
01:52:10,600 --> 01:52:15,171
ALSO IN HUMANS A DIFFERENCE OF

3177
01:52:15,171 --> 01:52:16,506
THE -- CNS, SO THE DIFFERENCE OF

3178
01:52:16,506 --> 01:52:20,310
THE MORPHOLOGY FOR THE --

3179
01:52:20,310 --> 01:52:21,878
>> WHAT I CAN DO IS PUT
YOU IN

3180
01:52:21,878 --> 01:52:22,946
TOUCH WITH CATHERINE SO IT WOULD

3181
01:52:22,946 --> 01:52:24,381
BE GREAT FOR YOU GUYS TO DISCUSS

3182
01:52:24,381 --> 01:52:24,581
THIS.

3183
01:52:24,581 --> 01:52:24,814
>> SURE.

3184
01:52:24,814 --> 01:52:25,248
THANK YOU.

3185
01:52:25,248 --> 01:52:27,117
>> BECAUSE WE'RE ALWAYS
LOOKING

3186
01:52:27,117 --> 01:52:29,085
FOR PEOPLE INTERESTED IN THE

3187
01:52:29,085 --> 01:52:30,754
SCIENCE TO BUILD OUR PROGRAM.

3188
01:52:30,754 --> 01:52:31,588
>> EXCELLENT.

3189
01:52:31,588 --> 01:52:34,558
ONE MORE QUESTION?

3190
01:52:34,558 --> 01:52:36,960
>> VERY EXCITING WORK.

3191
01:52:36,960 --> 01:52:40,230
WHY DON'T YOU THINK N-803 DID

3192
01:52:40,230 --> 01:52:40,664
ANYTHING?

3193
01:52:40,664 --> 01:52:42,399
IS IT LATENCY, LACK OF EXPOSURE,

3194
01:52:42,399 --> 01:52:46,770
WERE THE EFFECTS PERSISTENT?

3195
01:52:46,770 --> 01:52:48,405
WHAT ARE YOUR THOUGHTS ON THAT?

3196
01:52:48,405 --> 01:52:51,341
>> I THINK IT'S AN
IMPORTANT

3197
01:52:51,341 --> 01:52:52,375
QUESTION.

3198
01:52:52,375 --> 01:52:54,778
AND IT'S ALL SPECULATION AT THIS

3199
01:52:54,778 --> 01:52:57,047
POINT, BUT YOU KNOW, I CAN'T SAY

3200
01:52:57,047 --> 01:52:58,315
THAT IT DIDN'T DO ANYTHING

3201
01:52:58,315 --> 01:53:02,185
BECAUSE WE DID SEE IMPACTS ON NK

3202
01:53:02,185 --> 01:53:06,122
CELLS AND CD8 T-CELLS.

3203
01:53:06,122 --> 01:53:07,557
IN THAT GROUP, IN THAT STUDY

3204
01:53:07,557 --> 01:53:10,627
JUST DUE TO ANIMAL AVAILABILITY,

3205
01:53:10,627 --> 01:53:16,333
WE DIDN'T HAVE AN N-8 O803 ONLY

3206
01:53:16,333 --> 01:53:18,802
GROUP SO IT WAS GIVEN WITH THE

3207
01:53:18,802 --> 01:53:20,737
ANTIBODIES, AND IT IS POSSIBLE

3208
01:53:20,737 --> 01:53:22,272
THAT WE -- SINCE WE ONLY GAVE

3209
01:53:22,272 --> 01:53:23,673
ONE DOSE THAT YOU WOULD NEED

3210
01:53:23,673 --> 01:53:26,743
REPEATED DOSES TO REALLY GET THE

3211
01:53:26,743 --> 01:53:28,712
EFFECT THAT HAS BEEN DESCRIBED

3212
01:53:28,712 --> 01:53:31,348
IN ADULT MONKEY STUDIES IN TERMS

3213
01:53:31,348 --> 01:53:33,416
OF TRAFFICKING TO LYMPH NODES

3214
01:53:33,416 --> 01:53:35,719
AND HAVING A BETTER EFFECT ON

3215
01:53:35,719 --> 01:53:36,152
THE RESERVOIR.

3216
01:53:36,152 --> 01:53:37,787
IT'S REALLY HARD TO SAY.

3217
01:53:37,787 --> 01:53:40,490
>> DO YOU KNOW HOW LONG
THE

3218
01:53:40,490 --> 01:53:42,926
EFFECTS ON CELLS LASTED AFTER

3219
01:53:42,926 --> 01:53:43,660
SINGLE DOSE?

3220
01:53:43,660 --> 01:53:48,365
>> WELL, JUST LOOKING AT
KI67 BY

3221
01:53:48,365 --> 01:53:51,434
DAY 7, THE LEVELS KIND OF HAD

3222
01:53:51,434 --> 01:53:53,837
NORMALIZED.

3223
01:53:53,837 --> 01:53:55,138
AND WE DIDN'T HAVE SORT OF AN

3224
01:53:55,138 --> 01:53:56,473
EARLY TIME POINT WHERE WE LOOKED

3225
01:53:56,473 --> 01:53:58,208
AT THE LYMPH NODES SO I'M NOT

3226
01:53:58,208 --> 01:54:01,144
ABLE TO KIND OF SAY, BUT IF YOU

3227
01:54:01,144 --> 01:54:07,050
LOOK AT -- BEFORE WE GIVE N-8 OH

3228
01:54:07,050 --> 01:54:08,018
N-803 AND 8 WEEKS AFTER THERE'S

3229
01:54:08,018 --> 01:54:08,885
NO DIFFERENCE IN THE CELL TYPES

3230
01:54:08,885 --> 01:54:11,655
OR ACTIVATION BUT THAT'S QUITE A

3231
01:54:11,655 --> 01:54:11,888
LONG --

3232
01:54:11,888 --> 01:54:15,091
>> THE ATI WAS HOW LONG
AFTER

3233
01:54:15,091 --> 01:54:15,425
THE DOSE?

3234
01:54:15,425 --> 01:54:16,226
>> CLOSE TO A YEAR.

3235
01:54:16,226 --> 01:54:16,860
>> OKAY.

3236
01:54:16,860 --> 01:54:19,029
SO IT COULD HAVE WANED.

3237
01:54:19,029 --> 01:54:20,363
>> YEAH, FOR SURE.

3238
01:54:20,363 --> 01:54:21,131
>> OKAY.

3239
01:54:21,131 --> 01:54:22,999
THANK YOU SO MUCH TO EVERYONE.

3240
01:54:22,999 --> 01:54:26,636
AND I BELIEVE WE COME BACK AT

3241
01:54:26,636 --> 01:54:28,004
10:50.

3242
01:54:28,004 --> 01:54:31,941
>> ONCE AGAIN, THERE'S
BEVERAGES

3243
01:54:31,941 --> 01:54:33,877
OUTSIDE SPONSORED BY FAES, THE

3244
01:54:33,877 --> 01:54:35,211
FOUNDATION FOR ADVANCED

3245
01:54:35,211 --> 01:54:36,279
EDUCATION SCIENCES.

3246
01:54:36,279 --> 01:54:38,014
PLEASE CHECK OUT THEIR FLYERS

3247
01:54:38,014 --> 01:54:38,682
WHICH IS OUT THERE.

3248
01:54:38,682 --> 01:54:39,115
THANKS AGAIN.

3249
01:54:39,115 --> 01:54:40,750
SO WE'LL BE STICKING TO TIME, WE

3250
01:54:40,750 --> 01:54:42,185
HAVE A PACKED AGENDA.

3251
01:54:42,185 --> 01:54:44,861
PLEASE COME BACK AT 10:50. THANK
YOU.

3252
01:54:44,861 --> 01:54:46,630
SO HELLO, WE ARE

3253
01:54:46,630 --> 01:54:48,899
RESTARTING.

3254
01:54:48,899 --> 01:54:52,602
MY NAME IS BRIGITTE SANDERS,

3255
01:54:52,602 --> 01:54:53,904
PROGRAM OFFICER IN THE TARGETED

3256
01:54:53,904 --> 01:54:55,405
INTERVENTIONS BRANCH OF THE

3257
01:54:55,405 --> 01:54:58,441
DIVISION OF NIAID.

3258
01:54:58,441 --> 01:55:02,779
TOGETHER WITH MY COLLEAGUE, LEIA

3259
01:55:02,779 --> 01:55:03,113
NOVACK.

3260
01:55:03,113 --> 01:55:07,784
NEXT WE WILL HEAR A PRESENTATION

3261
01:55:07,784 --> 01:55:12,722
FROM THE I4C COLLABORATORY,

3262
01:55:12,722 --> 01:55:15,192
IMMUNOTHERAPY FOR HIV CURE.

3263
01:55:15,192 --> 01:55:17,527
THE I4C COLLABORATORY IS BASED

3264
01:55:17,527 --> 01:55:19,496
AT BETH ISRAEL DEACONESS MEDICAL

3265
01:55:19,496 --> 01:55:21,831
CENTER IN BOSTON AT THE

3266
01:55:21,831 --> 01:55:23,366
UNIVERSITY OF PITTSBURGH AND AT

3267
01:55:23,366 --> 01:55:25,068
THE MILITARY HIV RESEARCH

3268
01:55:25,068 --> 01:55:26,570
PROGRAM.

3269
01:55:26,570 --> 01:55:30,240
IN ADDITION TO DR. BAROUCH, WE

3270
01:55:30,240 --> 01:55:37,380
WILL HEAR PRESENTATIONS FROM DRY

3271
01:55:37,380 --> 01:55:44,921
VASAN, MILL  MITCHELL WARN FROMH

3272
01:55:44,921 --> 01:55:46,256
THAT I'LL HAND IT OVER TO YOU,

3273
01:55:46,256 --> 01:55:46,423
DAN.

3274
01:55:46,423 --> 01:55:46,923
>> THANK YOU VERY MUCH.

3275
01:55:46,923 --> 01:55:48,091
IT'S A PLEASURE TO BE HERE TODAY

3276
01:55:48,091 --> 01:55:54,331
WITH ALL THE OTHER NINE

3277
01:55:54,331 --> 01:55:55,098
COLLABORATORIES.

3278
01:55:55,098 --> 01:55:57,500
THE GOAL OF I4C IMMUNOTHERAPY

3279
01:55:57,500 --> 01:55:58,802
FOR CURE IS TO ADVANCE OUR

3280
01:55:58,802 --> 01:56:00,870
SCIENTIFIC UNDER AND STAG OF THE

3281
01:56:00,870 --> 01:56:03,073
VIER RESERVOIR AND TO DEVELOP

3282
01:56:03,073 --> 01:56:05,108
IMMUNOLOGIC STRATEGIES FOR HIV

3283
01:56:05,108 --> 01:56:06,776
REMISSION AND ERADICATION BY A

3284
01:56:06,776 --> 01:56:07,877
HIGHLY COLLABORATIVE AND

3285
01:56:07,877 --> 01:56:09,179
MULTIFACETED RESEARCH PROGRAM

3286
01:56:09,179 --> 01:56:10,614
INVOLVING PARTNERSHIPS AMONG

3287
01:56:10,614 --> 01:56:12,482
ACADEMIA, INDUSTRY, GOVERNMENT

3288
01:56:12,482 --> 01:56:14,217
AND COMMUNITY.

3289
01:56:14,217 --> 01:56:16,519
THE THREE JOINT PIs OF THIS

3290
01:56:16,519 --> 01:56:20,757
PROGRAM ARE SANDY, JOHN AND

3291
01:56:20,757 --> 01:56:22,092
MYSELF AND A LARGE LIST OF

3292
01:56:22,092 --> 01:56:22,959
HIGHLY OUTSTANDING INVESTIGATORS

3293
01:56:22,959 --> 01:56:24,728
ARE LISTED BELOW.

3294
01:56:24,728 --> 01:56:26,563
OUR HYPOTHESIS IS THAT MULTIPLE

3295
01:56:26,563 --> 01:56:27,530
IMMUNOLOGIC STRATEGIES WILL NEED

3296
01:56:27,530 --> 01:56:29,833
TO BE EXPLORED AND COMBINED TO

3297
01:56:29,833 --> 01:56:31,701
ACHIEVE LONG TERM ART-FREE

3298
01:56:31,701 --> 01:56:33,436
VIROLOGIC CONTROL, AND/OR

3299
01:56:33,436 --> 01:56:35,171
COMPLETE VIRUS ERADICATION WITH

3300
01:56:35,171 --> 01:56:36,973
A GOAL OF SELECTING COMBINATION

3301
01:56:36,973 --> 01:56:38,475
REGIMENS TO ADVANCE INTO

3302
01:56:38,475 --> 01:56:39,643
CLINICAL DEVELOPMENT.

3303
01:56:39,643 --> 01:56:43,146
OUR RESEARCH FOCI INVOLVE

3304
01:56:43,146 --> 01:56:44,581
MECHANISTIC BASIS OF RESERVOIR

3305
01:56:44,581 --> 01:56:46,549
TARGETING PERSISTENCE, NOVEL

3306
01:56:46,549 --> 01:56:47,751
STRATEGIES FOR SUSTAINED VIRUS

3307
01:56:47,751 --> 01:56:50,153
CONTROL AND NOVEL STRATEGIES FOR

3308
01:56:50,153 --> 01:56:52,455
VIRUS ERADICATION, AND THESE

3309
01:56:52,455 --> 01:56:55,091
GOALS WILL BE DESCRIBED IN THE

3310
01:56:55,091 --> 01:56:59,663
COMING TALKS.

3311
01:56:59,663 --> 01:57:01,531
OUR PRINCIPAL IMMUNOLOGIC

3312
01:57:01,531 --> 01:57:03,500
STRATEGY HAS BEEN THE USE OF

3313
01:57:03,500 --> 01:57:06,670
BROADLY NEUTRALIZING ANTIBODIES

3314
01:57:06,670 --> 01:57:09,039
WITH I -- AS WELL AS SOME NEW

3315
01:57:09,039 --> 01:57:11,708
CELL AR APPROACHES INCLUDING

3316
01:57:11,708 --> 01:57:13,109
CAR-T CELLS, ENGINEERED B CELLS

3317
01:57:13,109 --> 01:57:15,612
AND ENHANCED NK CELLS.

3318
01:57:15,612 --> 01:57:16,946
NOW AT THE MIDPOINT OF THE

3319
01:57:16,946 --> 01:57:18,448
GRANT, SOME OF THE SELECTED

3320
01:57:18,448 --> 01:57:20,083
HIGHLIGHTS THAT WE'LL DISCUSS

3321
01:57:20,083 --> 01:57:21,651
TODAY INVOLVE ADVANCES IN BASIC

3322
01:57:21,651 --> 01:57:23,053
RESEARCH ON RESERVOIR

3323
01:57:23,053 --> 01:57:24,821
CHARACTERIZATION FROM A

3324
01:57:24,821 --> 01:57:26,323
VIROLOGIC, IMMUNOLOGIC AND

3325
01:57:26,323 --> 01:57:28,058
MULTI-HE MIBG PERSPECTIVE, THE

3326
01:57:28,058 --> 01:57:32,562
DEVELOPMENT OF BNABS THERAPEUTIC

3327
01:57:32,562 --> 01:57:35,498
VACCINES, CAR-T CELLS,

3328
01:57:35,498 --> 01:57:37,467
ENGINEERED B CELLS AND ENHANCED

3329
01:57:37,467 --> 01:57:39,102
NK CELLS FOR CURE STRATEGIES,

3330
01:57:39,102 --> 01:57:40,403
COMBINATION OF ACTIVE AND

3331
01:57:40,403 --> 01:57:42,138
PASSIVE IMMUNIZATION FOR BOTH

3332
01:57:42,138 --> 01:57:43,673
DELAYED VIRAL REBOUND AND

3333
01:57:43,673 --> 01:57:46,543
VIROLOGIC CONTROL IN NON-HUMAN

3334
01:57:46,543 --> 01:57:47,844
PRIMATE SWRELS ENS HANSED

3335
01:57:47,844 --> 01:57:50,046
COMMUNITY ENGAGEMENT AND CAB

3336
01:57:50,046 --> 01:57:50,580
ACTIVITIES.

3337
01:57:50,580 --> 01:57:54,184
SANDY V VASAN WILL DISCUSS RF 1,

3338
01:57:54,184 --> 01:57:55,518
MECHANISTIC BASIS OF VIRAL

3339
01:57:55,518 --> 01:57:58,455
PERSISTENCE, LEARNING  LEARNINGI

3340
01:57:58,455 --> 01:58:01,958
STUDIES, JOHN MELLORS WILL SPEAK

3341
01:58:01,958 --> 01:58:03,460
ON EXPLORING INNOVATIVE

3342
01:58:03,460 --> 01:58:04,694
APPROACHES TO CONTROL AND

3343
01:58:04,694 --> 01:58:07,530
ELIMINATE HIV RESERVOIRS, I WILL

3344
01:58:07,530 --> 01:58:11,534
PROVIDE AN UPDATE ON RF 3, AND

3345
01:58:11,534 --> 01:58:12,869
JESSICA SALZWEDEL WILL DISCUSS

3346
01:58:12,869 --> 01:58:15,638
COMMUNITY ENGAGEMENT IN I4C.

3347
01:58:15,638 --> 01:58:19,976
WE'RE ALSO PROUD WE HAVE

3348
01:58:19,976 --> 01:58:24,414
SCHOLARSSCHOLARSHIP RECIPIENT HD

3349
01:58:24,414 --> 01:58:25,014
WHO HAVE POSTERS.

3350
01:58:25,014 --> 01:58:26,216
I WOULD ENCOURAGE YOU TO SPEND

3351
01:58:26,216 --> 01:58:27,450
TIME AT THOSE POSTERS AND THE

3352
01:58:27,450 --> 01:58:29,352
WORK OF THESE THREE OUTSTANDING

3353
01:58:29,352 --> 01:58:30,754
JUNIOR INVESTIGATORS, AS WELL AS

3354
01:58:30,754 --> 01:58:32,021
MANY OTHERS, ARE GOING TO BE

3355
01:58:32,021 --> 01:58:34,557
HIGHLIGHTED IN THE COMING TALKS.

3356
01:58:34,557 --> 01:58:36,292
AND WITH THAT, I'LL TURN IT OVER

3357
01:58:36,292 --> 01:58:42,866
TO SANDY.

3358
01:58:42,866 --> 01:58:44,167
>> THANKS, DAN.

3359
01:58:44,167 --> 01:58:48,304
SO RF 1 IS THE MECHANISTIC

3360
01:58:48,304 --> 01:58:49,739
FOCUS, I WON'T READ THE

3361
01:58:49,739 --> 01:58:51,374
HYPOTHESIS HERE VERBATIM, BUT

3362
01:58:51,374 --> 01:58:53,209
IT'S LED BY JOHN MELLORS, ALEX

3363
01:58:53,209 --> 01:58:57,747
AND MYSELF, AND WE ARE HONORED

3364
01:58:57,747 --> 01:59:08,191
TO HAVE A PHENOMENAL TEAM.

3365
01:59:08,491 --> 01:59:11,928
SO TO SUMMARIZE, THE NEXT 10

3366
01:59:11,928 --> 01:59:13,963
MINUTES WILL FOCUS ON TWO

3367
01:59:13,963 --> 01:59:15,565
APPROACHES OR TWO STORIES, I

3368
01:59:15,565 --> 01:59:16,199
SHOULD SAY.

3369
01:59:16,199 --> 01:59:17,934
THE FIRST IS TO STUDY THE

3370
01:59:17,934 --> 01:59:20,136
RESERVOIR, THE HIV RESERVOIR IN

3371
01:59:20,136 --> 01:59:21,704
PEOPLE WHO ARE LIVING WITH HIV

3372
01:59:21,704 --> 01:59:24,274
AND ARE WELL SUPPRESSED ON ART.

3373
01:59:24,274 --> 01:59:25,909
AND THE BOTTOM LINE OF WHAT

3374
01:59:25,909 --> 01:59:30,079
WE'RE FINDING IS THAT HOW EARLY

3375
01:59:30,079 --> 01:59:32,582
YOU START ART AFTER INITIAL

3376
01:59:32,582 --> 01:59:35,218
INFECTION DOES AFFECT THE

3377
01:59:35,218 --> 01:59:38,388
RESERVOIR, AND WITH EARLIER --

3378
01:59:38,388 --> 01:59:39,689
STARTING ART EARLIER, REDUCING

3379
01:59:39,689 --> 01:59:41,658
THE SIZE OF THE RESERVOIR, AND

3380
01:59:41,658 --> 01:59:43,326
THIS RESERVOIR, EVEN FOR PEOPLE

3381
01:59:43,326 --> 01:59:46,329
WHO ARE ON ART, VARIES OVER TIME

3382
01:59:46,329 --> 01:59:47,897
IN DIFFERING PATTERNS, WHICH IS

3383
01:59:47,897 --> 01:59:48,898
CONSISTENT WITH THE THEME OF

3384
01:59:48,898 --> 01:59:50,300
WHAT WE'VE BEEN HEARING OVER THE

3385
01:59:50,300 --> 01:59:50,967
LAST DAY AND A HALF.

3386
01:59:50,967 --> 01:59:52,435
AND THE STUDIES WE'VE CONDUCTED

3387
01:59:52,435 --> 01:59:53,803
TO DATE HAVE FOCUSED ON THE

3388
01:59:53,803 --> 01:59:54,938
BLOOD BUT WE'RE VERY EXCITED

3389
01:59:54,938 --> 01:59:56,206
THAT WE'RE NOW TURNING THESE

3390
01:59:56,206 --> 01:59:58,408
ANALYSES TO THE BRAIN TO SEE

3391
01:59:58,408 --> 02:00:00,577
WHETHER THOSE SAME PATTERNS

3392
02:00:00,577 --> 02:00:00,777
HOLD.

3393
02:00:00,777 --> 02:00:01,711
AND THEN THE SECOND PART OF THE

3394
02:00:01,711 --> 02:00:04,214
STORY IS ACTUALLY TO CO TO DO WE

3395
02:00:04,214 --> 02:00:05,615
CALL CORRELATES WORK, AND THAT'S

3396
02:00:05,615 --> 02:00:08,051
REALLY TO SEE IF WE CAN LOOK AT

3397
02:00:08,051 --> 02:00:09,886
PREDICTORS OF THE RESERVOIR OR

3398
02:00:09,886 --> 02:00:11,654
OTHER MARKERS THAT MAY

3399
02:00:11,654 --> 02:00:13,189
CORRESPOND TO THE TIME IT TAKES

3400
02:00:13,189 --> 02:00:14,757
FOR THE VIRUS TO COME BACK IN

3401
02:00:14,757 --> 02:00:17,460
THE BLOOD OR REBOUND AFTER

3402
02:00:17,460 --> 02:00:19,863
STOPPING -- A PARTICIPANT STOP

3403
02:00:19,863 --> 02:00:20,430
ART.

3404
02:00:20,430 --> 02:00:21,731
AND AGAIN WE LEVERAGE BOTH

3405
02:00:21,731 --> 02:00:23,199
ANIMAL AND HUMAN MODELS TO LOOK

3406
02:00:23,199 --> 02:00:25,668
AT THIS.

3407
02:00:25,668 --> 02:00:29,706
SO TO JUMP INTO THE FIRST STORY,

3408
02:00:29,706 --> 02:00:31,007
WHICH IS A COLLABORATION LED BY

3409
02:00:31,007 --> 02:00:34,811
BOB AND JANET SILICANO WITH DAN

3410
02:00:34,811 --> 02:00:38,014
BAROUCH AND LED BY DR. EMILY

3411
02:00:38,014 --> 02:00:39,315
FREY, 10 RHESUS MACAQUES WHO

3412
02:00:39,315 --> 02:00:43,920
WERE INFECTED WITH SIV MACK

3413
02:00:43,920 --> 02:00:45,755
231 WERE LEFT UNTREATED FOR 48

3414
02:00:45,755 --> 02:00:47,223
WEEKS BEFORE STARTING ART.

3415
02:00:47,223 --> 02:00:50,393
AND THAT'S IMPORTANT BECAUSE

3416
02:00:50,393 --> 02:00:52,795
BOTH FOR SCIENTIFIC REASONS AND

3417
02:00:52,795 --> 02:00:54,664
FRANKLY RESOURCE REASONS, MANY

3418
02:00:54,664 --> 02:00:58,268
OF THESE NHP STUDIES START ART

3419
02:00:58,268 --> 02:01:00,970
SOON AFTER INFECTION, BUT THIS

3420
02:01:00,970 --> 02:01:03,273
MODEL ACTUALLY BETTER

3421
02:01:03,273 --> 02:01:04,140
RECAPITULATES THE VAST MAJORITY

3422
02:01:04,140 --> 02:01:05,341
OF PEOPLE LIVING WITH HIV.

3423
02:01:05,341 --> 02:01:06,743
SO AFTER THAT 48 WEEKS, THEN

3424
02:01:06,743 --> 02:01:09,712
THEY WERE STARTED ON ART AND

3425
02:01:09,712 --> 02:01:11,047
MAINTAINING AND FOLLOWED FOR

3426
02:01:11,047 --> 02:01:12,248
FIVE YEARS SO THAT GAVE THE

3427
02:01:12,248 --> 02:01:14,517
INVESTIGATORS THE ABILITY TO

3428
02:01:14,517 --> 02:01:15,952
LOOK AT THE RESERVOIR IN DETAIL,

3429
02:01:15,952 --> 02:01:17,487
BOTH THROUGH QUANTITATIVE

3430
02:01:17,487 --> 02:01:19,222
MEASURES LIKE DIGITAL DROPLET

3431
02:01:19,222 --> 02:01:21,858
PCR AND QUALITATIVELY WITH

3432
02:01:21,858 --> 02:01:23,192
SINGLE GENOME SEQUENCING OVER

3433
02:01:23,192 --> 02:01:27,397
THE EXTENDED ART.

3434
02:01:27,397 --> 02:01:28,765
SO THE QUICK BOTTOM LINE HERE IS

3435
02:01:28,765 --> 02:01:30,366
THAT THE DECAY OF THESE INTACT

3436
02:01:30,366 --> 02:01:35,271
PRO VIRUSES ON ART WAS

3437
02:01:35,271 --> 02:01:37,240
MULTIPHASIC, IN THIS MODEL

3438
02:01:37,240 --> 02:01:38,808
TRIPHASIC SO YOU CAN SEE ACROSS

3439
02:01:38,808 --> 02:01:42,178
DIFFERENT NHPs THERE'S INITIAL

3440
02:01:42,178 --> 02:01:43,379
RAPID DECAY FOLLOWED BY SLOWER

3441
02:01:43,379 --> 02:01:44,781
DECAY AND ULTIMATELY MORE OF A

3442
02:01:44,781 --> 02:01:47,784
PLATEAU TYPE OF DECAY.

3443
02:01:47,784 --> 02:01:50,486
AND WHAT THIS MEANS TO US IS

3444
02:01:50,486 --> 02:01:52,488
THAT THERE IS A LABEL POPULATION

3445
02:01:52,488 --> 02:01:54,457
THAT GOES AWAY QUICKLY, AND THEN

3446
02:01:54,457 --> 02:01:56,125
A POPULATION THAT IS MORE

3447
02:01:56,125 --> 02:01:57,860
RELATED TO THE ANCESTRAL

3448
02:01:57,860 --> 02:01:58,895
VARIANTS OF INITIAL INFECTIONS

3449
02:01:58,895 --> 02:02:00,363
THAT PERSIST.

3450
02:02:00,363 --> 02:02:02,398
FURTHERMORE, THAT AS YOU CAN SEE

3451
02:02:02,398 --> 02:02:04,200
IN THE THIRD BULLET, THE

3452
02:02:04,200 --> 02:02:06,402
EVIDENCE FOR PROLIFERATION OF

3453
02:02:06,402 --> 02:02:08,037
THESE INFECTED CELLS BECOMES

3454
02:02:08,037 --> 02:02:09,105
MORE APPARENT OVER TIME, AND

3455
02:02:09,105 --> 02:02:11,441
WHAT THAT MEANS IS THAT THERE'S

3456
02:02:11,441 --> 02:02:14,243
MORE LIKELY TO BE PROLIFERATION

3457
02:02:14,243 --> 02:02:15,678
OF MORE CLONAL POPULATIONS OR

3458
02:02:15,678 --> 02:02:19,215
WHAT JOHN MIGHT CALL A

3459
02:02:19,215 --> 02:02:20,516
REPLICLONE AS YOU GO FURTHER OUT

3460
02:02:20,516 --> 02:02:21,484
INTO ART.

3461
02:02:21,484 --> 02:02:23,720
THIS SUGGESTS THAT THE RESERVOIR

3462
02:02:23,720 --> 02:02:26,022
IN ART IS BEING RECEDED THROUGH

3463
02:02:26,022 --> 02:02:28,291
THIS PROLIFERATIVE MECHANISM.

3464
02:02:28,291 --> 02:02:29,993
SO MOVING TO THE SECOND PART OF

3465
02:02:29,993 --> 02:02:34,330
THE RESERVOIR STUDY IN HUMANS

3466
02:02:34,330 --> 02:02:44,507
CON JECTED  --LOOKING AT THE SAF

3467
02:02:44,507 --> 02:02:49,512
DECAY IN HUMANS ON

3468
02:02:49,512 --> 02:02:51,714
ACTG5321 WHICH IS AN ACTG COHORT

3469
02:02:51,714 --> 02:02:54,550
OF PEOPLE LARGELY SUBTYPE B

3470
02:02:54,550 --> 02:02:57,387
CHRONICALLY LIVING WITH HIV, AND

3471
02:02:57,387 --> 02:02:59,255
I APOLOGIZE BECAUSE THERE'S TWO

3472
02:02:59,255 --> 02:03:00,490
MORE FIGURES TO THIS PANEL THAT

3473
02:03:00,490 --> 02:03:02,558
DIDN'T COME THROUGH IN THE PDF

3474
02:03:02,558 --> 02:03:03,326
CONVERSION SO YOU'LL HAVE TO

3475
02:03:03,326 --> 02:03:05,495
TAKE MY WORD FOR IT OR FIND JOHN

3476
02:03:05,495 --> 02:03:07,296
OR JOSH AFTERWARDS, BUT

3477
02:03:07,296 --> 02:03:09,365
BASICALLY THAT THERE ARE VARYING

3478
02:03:09,365 --> 02:03:12,535
PATTERNS OF DECAY, AND AGAIN,

3479
02:03:12,535 --> 02:03:13,870
IT'S NICELY COMPLEMENTARY TO THE

3480
02:03:13,870 --> 02:03:15,071
MONKEY WORK I JUST SHOWED,

3481
02:03:15,071 --> 02:03:18,241
SHOWING THAT THERE CAN BE BOTH

3482
02:03:18,241 --> 02:03:19,442
THE SLOPE THAT YOU SEE THERE,

3483
02:03:19,442 --> 02:03:22,612
BUT THEN ALSO A SUBSET OF PEOPLE

3484
02:03:22,612 --> 02:03:23,813
WHO HAVE LATE INCREASES.

3485
02:03:23,813 --> 02:03:26,582
AND YOU'LL SEE THAT IN A

3486
02:03:26,582 --> 02:03:26,983
SUBSEQUENT SLIDE.

3487
02:03:26,983 --> 02:03:28,084
SO YOU DON'T HAVE TO JUST TAKE

3488
02:03:28,084 --> 02:03:30,386
MY WORD FOR IT.

3489
02:03:30,386 --> 02:03:33,022
BUT THE KEY QUESTIONS THAT WERE

3490
02:03:33,022 --> 02:03:36,559
ASKED WITH THIS PART OF THE

3491
02:03:36,559 --> 02:03:41,130
STUDY WAS THAT THE INFECTED CELL

3492
02:03:41,130 --> 02:03:49,338
CLONES, USING TWO DIFFERENT

3493
02:03:49,338 --> 02:03:50,873
MEASURES, PAINSTAKINGLY

3494
02:03:50,873 --> 02:03:51,974
CHARACTERIZING SOME OF THESE

3495
02:03:51,974 --> 02:03:54,711
CLONES BOTH BY IPDA AND THEN

3496
02:03:54,711 --> 02:03:56,479
THROUGH INTEGRATION SITE

3497
02:03:56,479 --> 02:03:57,680
ANALYSES, INCLUDING CUSTOMIZED

3498
02:03:57,680 --> 02:03:59,549
PRIMERS FOR THOSE CLONES THAT

3499
02:03:59,549 --> 02:04:00,616
WERE -- WHERE THE INTEGRATION

3500
02:04:00,616 --> 02:04:03,286
SITES WERE MAPPED CHARACTERIZE

3501
02:04:03,286 --> 02:04:04,721
THE PATTERN OF VARIABILITY OF

3502
02:04:04,721 --> 02:04:06,589
THESE CLONES OVER TIME.

3503
02:04:06,589 --> 02:04:08,124
AND THOSE WHO HAD PERSISTENT

3504
02:04:08,124 --> 02:04:08,891
CLONES.

3505
02:04:08,891 --> 02:04:10,860
AND SO FOCUSING HERE WITH JUST

3506
02:04:10,860 --> 02:04:13,830
ONE EXAMPLE OF TWO INDIVIDUALS

3507
02:04:13,830 --> 02:04:15,898
WHO WERE IN THAT LATE INCREASE

3508
02:04:15,898 --> 02:04:17,967
IN COHORT, WHICH WE ALSO HEARD

3509
02:04:17,967 --> 02:04:19,836
ABOUT A LITTLE BIT YESTERDAY,

3510
02:04:19,836 --> 02:04:22,805
THOSE INDIVIDUALS WERE BOTH

3511
02:04:22,805 --> 02:04:24,774
ANALYZED BY SINGLE COPY ANALYSIS

3512
02:04:24,774 --> 02:04:26,642
AND INTEGRATION SITE ANALYSIS,

3513
02:04:26,642 --> 02:04:28,077
AND THERE ARE MANY MORE

3514
02:04:28,077 --> 02:04:29,278
INDIVIDUALS WHO ARE BEING

3515
02:04:29,278 --> 02:04:30,480
CHARACTERIZED THIS WAY, BUT JUST

3516
02:04:30,480 --> 02:04:31,380
TO GIVE YOU A SNAPSHOT OF THIS

3517
02:04:31,380 --> 02:04:33,015
WORK IN PROGRESS, YOU CAN SEE

3518
02:04:33,015 --> 02:04:35,752
THAT THE FIRST PARTICIPANT,

3519
02:04:35,752 --> 02:04:38,721
THERE ARE TWO CLONES, BUT

3520
02:04:38,721 --> 02:04:39,689
THERE'S NOTHING THAT'S REALLY

3521
02:04:39,689 --> 02:04:40,890
PULLING OUT THAT'S DOMINANT,

3522
02:04:40,890 --> 02:04:42,091
WHEREAS THE SECOND PARTICIPANT,

3523
02:04:42,091 --> 02:04:45,394
THERE ARE MULTIPLE PROBABLE

3524
02:04:45,394 --> 02:04:46,496
CLONES AND IMPORTANTLY THE

3525
02:04:46,496 --> 02:04:47,463
INTEGRATION SITE ANALYSIS IS

3526
02:04:47,463 --> 02:04:48,898
PICKING UP CLONES THAT MIGHT NOT

3527
02:04:48,898 --> 02:04:51,300
HAVE BEEN PICKED UP BY IPDA.

3528
02:04:51,300 --> 02:04:53,202
AND IT JUST EMPHASIZES THE FACT

3529
02:04:53,202 --> 02:04:55,371
THAT WE NEED TO TAKE MULTIPLE

3530
02:04:55,371 --> 02:04:58,207
APPROACHES TO CHARACTERIZING THE

3531
02:04:58,207 --> 02:04:59,475
RESERVOIR RATHER THAN RELYING ON

3532
02:04:59,475 --> 02:05:00,643
ONE WINNER ASSAY.

3533
02:05:00,643 --> 02:05:02,278
SO THAT WORK WILL BE ONGOING,

3534
02:05:02,278 --> 02:05:03,946
AND YOU'LL HEAR MORE ABOUT IT AT

3535
02:05:03,946 --> 02:05:07,216
OUR NEXT UPDATE.

3536
02:05:07,216 --> 02:05:09,085
THIS THEN RELATES BACK TO THE

3537
02:05:09,085 --> 02:05:13,456
COHORTS THAT WE AT MHRP ARE ALSO

3538
02:05:13,456 --> 02:05:14,223
WORKING WITH.

3539
02:05:14,223 --> 02:05:17,393
I SERVE AS PROTOCOL CHAIR FOR

3540
02:05:17,393 --> 02:05:19,362
RV254, WHICH IS AN INCREDIBLE

3541
02:05:19,362 --> 02:05:20,797
COHORT OF PEOPLE IN THAILAND WHO

3542
02:05:20,797 --> 02:05:22,665
HAVE BEEN DIAGNOSED AND STARTED

3543
02:05:22,665 --> 02:05:24,634
ON ART VERY, VERY EARLY DURING

3544
02:05:24,634 --> 02:05:29,005
ACUTE OR EARLY HIV

3545
02:05:29,005 --> 02:05:29,872
IDENTIFICATION, AND THE

3546
02:05:29,872 --> 02:05:31,174
STATISTICS SPEAK FOR THEMSELVES

3547
02:05:31,174 --> 02:05:33,843
BUT THIS IS A LARGE COHORT OF

3548
02:05:33,843 --> 02:05:38,214
PEOPLE WHO HAVE -- WITH OVER 90%

3549
02:05:38,214 --> 02:05:40,082
RETENTION NOW GETTING INTO ITS

3550
02:05:40,082 --> 02:05:42,819
15TH YEAR WHO ARE JUST KIND

3551
02:05:42,819 --> 02:05:45,988
ENOUGH TO AGREE TO MULTIPLE

3552
02:05:45,988 --> 02:05:47,657
PROCEDURES, AND WE ARE NOW,

3553
02:05:47,657 --> 02:05:48,858
BASED ON THE DATA THAT YOU'VE

3554
02:05:48,858 --> 02:05:50,293
BEEN HEARING, EXTENDING THE

3555
02:05:50,293 --> 02:05:51,794
FOLLOW-UP IN THIS COHORT FROM 15

3556
02:05:51,794 --> 02:05:52,929
TO 20 YEARS SO THAT WE CAN

3557
02:05:52,929 --> 02:05:53,796
CONTINUE TO ASK SOME OF THESE

3558
02:05:53,796 --> 02:05:57,099
QUESTIONS.

3559
02:05:57,099 --> 02:05:58,868
 IN THAT COHORT, AGAIN

3560
02:05:58,868 --> 02:06:01,170
AS COLLABORATIVE AND RECIPROCAL

3561
02:06:01,170 --> 02:06:04,640
VALIDATION.

3562
02:06:04,640 --> 02:06:06,275
NOW SWITCHING FROM THE RESERVOIR

3563
02:06:06,275 --> 02:06:07,643
STUDIES TO SOME OF THE ATI

3564
02:06:07,643 --> 02:06:09,278
CORRELATE STUDIES, THIS HAS ALSO

3565
02:06:09,278 --> 02:06:11,447
SERVED AS A BASIS FOR FOUR

3566
02:06:11,447 --> 02:06:12,849
SEPARATE ATI CLINICAL TRIALS TO

3567
02:06:12,849 --> 02:06:14,016
DATE WITH VARYING INTERVENTIONS

3568
02:06:14,016 --> 02:06:15,318
OR NO INTERVENTION IN THE CASE

3569
02:06:15,318 --> 02:06:16,619
OF THE FIRST STUDY.

3570
02:06:16,619 --> 02:06:18,287
ALL OF THESE STUDIES HAVE BEEN

3571
02:06:18,287 --> 02:06:19,155
PUBLISHED AND PRESENTED SO I'M

3572
02:06:19,155 --> 02:06:20,489
NOT GOING TO GO THROUGH THEM

3573
02:06:20,489 --> 02:06:22,892
HERE IN DETAIL, BUT RATHER USE

3574
02:06:22,892 --> 02:06:23,993
THIS SLIDE AS A BASIS TO TALK

3575
02:06:23,993 --> 02:06:26,629
ABOUT WHAT WE'RE DOING TO LOOK

3576
02:06:26,629 --> 02:06:29,031
IN AGGREGATE AT THE MAJORITY OF

3577
02:06:29,031 --> 02:06:30,900
THESE PARTICIPANTS IN ANALYZING

3578
02:06:30,900 --> 02:06:33,536
CORRELATES TO VIRAL REBOUND.

3579
02:06:33,536 --> 02:06:35,037
AND SO WHAT WAS JUST PUBLISHED

3580
02:06:35,037 --> 02:06:40,977
THIS YEAR IN THE LABORATORY AT

3581
02:06:40,977 --> 02:06:44,146
MHRP IS THAT IF YOU LOOKED AT

3582
02:06:44,146 --> 02:06:46,749
EARLY CLINICAL PREDICTORS YEARS

3583
02:06:46,749 --> 02:06:49,218
BEFORE THESE PEOPLE WENT ON ATI

3584
02:06:49,218 --> 02:06:50,319
BUT BEFORE THEY STARTED ART,

3585
02:06:50,319 --> 02:06:51,821
THAT PEOPLE WHO HAD HIGHER

3586
02:06:51,821 --> 02:06:53,923
INITIAL VIREMIA AND WHO TOOK

3587
02:06:53,923 --> 02:06:55,892
LONGER TO SUPPRESS POST ART WERE

3588
02:06:55,892 --> 02:06:58,427
MORE LIKELY TO REBOUND EARLIER,

3589
02:06:58,427 --> 02:07:00,596
WHICH WE BELIEVE IS A SURROGATE

3590
02:07:00,596 --> 02:07:01,964
TO THAT LARGER INITIAL SEEDING

3591
02:07:01,964 --> 02:07:02,698
OF THE RESERVOIR.

3592
02:07:02,698 --> 02:07:04,567
AND SO I SHOW THE PICTURES OF

3593
02:07:04,567 --> 02:07:05,635
THE INVESTIGATORS HERE BECAUSE

3594
02:07:05,635 --> 02:07:07,436
NOT ONLY TO ACKNOWLEDGE THEIR

3595
02:07:07,436 --> 02:07:08,838
WORK BUT ALSO BECAUSE THEY ARE

3596
02:07:08,838 --> 02:07:11,007
ALL HERE AND SO FOR THOSE OF YOU

3597
02:07:11,007 --> 02:07:11,574
ESPECIALLY THOSE IN THE

3598
02:07:11,574 --> 02:07:13,409
COMMUNITY WHO WANT TO LEARN

3599
02:07:13,409 --> 02:07:14,543
MORE, PLEASE I ENCOURAGE YOU TO

3600
02:07:14,543 --> 02:07:17,046
FIND THEM IN THE HALLWAYS IN THE

3601
02:07:17,046 --> 02:07:17,947
BREAKS BECAUSE THEY'LL BE

3602
02:07:17,947 --> 02:07:19,015
EXCITED TO TALK MORE ABOUT THEIR

3603
02:07:19,015 --> 02:07:19,482
WORK.

3604
02:07:19,482 --> 02:07:21,651
BUT BUILDING ON THIS, THEN,

3605
02:07:21,651 --> 02:07:26,155
WE'RE MOVING TO LOOK AT THE

3606
02:07:26,155 --> 02:07:27,590
POTENTIAL IMMUNOLOGIC, VIROLOGIC

3607
02:07:27,590 --> 02:07:28,658
AND OTHER LABORATORY CORRELATES

3608
02:07:28,658 --> 02:07:31,127
OF TIME TO VIRAL REBOUND.

3609
02:07:31,127 --> 02:07:33,629
AND SO IN COLLABORATION WITH

3610
02:07:33,629 --> 02:07:37,700
JOHN AND JOSH, WE UTILIZED THE

3611
02:07:37,700 --> 02:07:41,404
SINGLE COPY ASSAY TO LOOK AT

3612
02:07:41,404 --> 02:07:45,374
PRESENCE OF VIRUS ON PEOPLE BY

3613
02:07:45,374 --> 02:07:46,242
STANDARD CLINICAL MEASUREMENTS

3614
02:07:46,242 --> 02:07:47,576
WELL SUPPRESSED ON ART AND

3615
02:07:47,576 --> 02:07:48,778
FINDING, IF YOU FOLLOW THOSE RED

3616
02:07:48,778 --> 02:07:50,313
BARS ON THE LEFT PANEL, YOU CAN

3617
02:07:50,313 --> 02:07:53,916
SEE THAT PEOPLE WHO STARTED ART

3618
02:07:53,916 --> 02:07:58,721
IF LATER FIEBIG STAGES WERE MORE

3619
02:07:58,721 --> 02:08:00,389
LIKELY TO HAVE PROTECTIVE

3620
02:08:00,389 --> 02:08:02,058
VIREMIA ON A SINGLE COPY ASSAY

3621
02:08:02,058 --> 02:08:04,460
WHILE BEING SUPPRESSED ON ART BY

3622
02:08:04,460 --> 02:08:05,227
STANDARD MEASURES.

3623
02:08:05,227 --> 02:08:06,996
AND FURTHERMORE, THAT THAT

3624
02:08:06,996 --> 02:08:08,965
SINGLE COPY ASSAY PREATI

3625
02:08:08,965 --> 02:08:10,266
CORRELATES TO TIME TO VIRAL

3626
02:08:10,266 --> 02:08:11,233
REBOUND AS YOU CAN SEE ON THE

3627
02:08:11,233 --> 02:08:14,904
LEFT PANEL.

3628
02:08:14,904 --> 02:08:16,005
SO AS I MENTIONED IN THE

3629
02:08:16,005 --> 02:08:17,540
SUMMARY, WE'RE NOW LEVERAGING

3630
02:08:17,540 --> 02:08:21,243
THE NIMH-FUNDED COLLECTION OF

3631
02:08:21,243 --> 02:08:29,251
CSF AND CELLS IN SUPERNATEN WITH

3632
02:08:29,251 --> 02:08:31,787
SERENA AND LYDIE TO HOW THIS

3633
02:08:31,787 --> 02:08:32,855
MIGHT TRANSLATE TO THE

3634
02:08:32,855 --> 02:08:33,723
NEUROLOGIC COMPARTMENT.

3635
02:08:33,723 --> 02:08:36,392
AND THEN THE FINAL SLIDE I HAVE

3636
02:08:36,392 --> 02:08:38,894
IS TO BRING IT BACK, AGAIN, THIS

3637
02:08:38,894 --> 02:08:40,663
CORRELATES WORK IS AGAIN

3638
02:08:40,663 --> 02:08:46,802
COMPLEMENTARY TO THE WORK BEING

3639
02:08:46,802 --> 02:08:55,444
DONE BY MALIKA AID BOUDRIES,

3640
02:08:55,444 --> 02:09:03,119
PERIPHERAL BIOMARKERS OF VIRAL

3641
02:09:03,119 --> 02:09:04,520
REBOUND IN RHESUS MACAQUES, A

3642
02:09:04,520 --> 02:09:06,088
STUDY OF VARIOUS INTERVENTIONS

3643
02:09:06,088 --> 02:09:07,823
IN MACAQUES WHO BOTH HAD

3644
02:09:07,823 --> 02:09:09,158
CONTROLLERS AND REBOUNDERS, AND

3645
02:09:09,158 --> 02:09:11,594
JUST IN A BINARY WAY LOOKING AT

3646
02:09:11,594 --> 02:09:12,828
THOSE TWO SUBSETS AND

3647
02:09:12,828 --> 02:09:14,263
IDENTIFYING GENETIC SIGNATURES

3648
02:09:14,263 --> 02:09:16,165
THAT ARE PREDICTIVE OF REBOUND,

3649
02:09:16,165 --> 02:09:20,736
IN ADDITION TO CELLULAR MARKERS

3650
02:09:20,736 --> 02:09:23,472
POST STOPPING ART THAT THEN

3651
02:09:23,472 --> 02:09:24,540
PREDICTED REBOUND.

3652
02:09:24,540 --> 02:09:26,242
SO ALL OF THESE MEASURES ARE

3653
02:09:26,242 --> 02:09:29,311
TRYING TO HELP US UNDERSTAND THE

3654
02:09:29,311 --> 02:09:31,280
RESERVOIR, AND THE PATHOGENESIS

3655
02:09:31,280 --> 02:09:33,682
THAT CAN HELP US THEN DEVELOP

3656
02:09:33,682 --> 02:09:36,085
BETTER INTERVENTIONS TO ATTACK

3657
02:09:36,085 --> 02:09:39,622
CURE, WHICH TURNS US OVER TO RF

3658
02:09:39,622 --> 02:09:39,755
2.

3659
02:09:39,755 --> 02:09:46,395
[APPLAUSE]

3660
02:09:46,395 --> 02:09:47,630
>> IT'S REALLY A PRIVILEGE
TO BE

3661
02:09:47,630 --> 02:09:51,700
ABLE TO PRESENT SOME INNOVATIVE

3662
02:09:51,700 --> 02:09:54,303
WORK LISTED HERE.

3663
02:09:54,303 --> 02:09:56,205
THE OBJECTIVES HERE ARE TO

3664
02:09:56,205 --> 02:09:58,607
ASSESS NEW TECHNOLOGIES,

3665
02:09:58,607 --> 02:10:01,577
RECOGNIZING THAT THEY HAVE RISK

3666
02:10:01,577 --> 02:10:03,279
BECAUSE THEY'RE UNPROVEN, BUT

3667
02:10:03,279 --> 02:10:04,180
HAVE THE PROMISE OF CONTROLLING

3668
02:10:04,180 --> 02:10:08,684
OR HELPING TO ERADICATE HIV.

3669
02:10:08,684 --> 02:10:10,252
THE SUMMARY IS SIMPLE.

3670
02:10:10,252 --> 02:10:11,020
A MULTIPRONGED APPROACH IS

3671
02:10:11,020 --> 02:10:13,322
LIKELY NEEDED TO CONTROL OR

3672
02:10:13,322 --> 02:10:13,956
ELIMINATE HIV.

3673
02:10:13,956 --> 02:10:16,525
THE QUESTION IS, CAN WE ENGINEER

3674
02:10:16,525 --> 02:10:19,261
T-CELLS, B CELLS, OR ENHANCE NK

3675
02:10:19,261 --> 02:10:21,764
CELLS TO CONTROL OR ELIMINATE

3676
02:10:21,764 --> 02:10:22,331
HIV?

3677
02:10:22,331 --> 02:10:25,634
SOME APPROACHES ARE PROMISING,

3678
02:10:25,634 --> 02:10:27,069
BUT REFINEMENT AND FURTHER PROOF

3679
02:10:27,069 --> 02:10:30,372
OF CON ACCEP CONCEPT IS NEEDED.

3680
02:10:30,372 --> 02:10:31,674
WE'RE AT A CRITICAL JUNCTURE

3681
02:10:31,674 --> 02:10:33,109
WITH THIS WORK WHERE WE'RE DOING

3682
02:10:33,109 --> 02:10:38,147
PROOF OF CONCEPT STUDIES IN NHP

3683
02:10:38,147 --> 02:10:38,814
MODELS.

3684
02:10:38,814 --> 02:10:40,549
SO FIRST JIM RILEY HAS LED A

3685
02:10:40,549 --> 02:10:44,487
GROUP TO ENGINEER T-CELLS BY

3686
02:10:44,487 --> 02:10:48,657
INTRODUCING VECTOR THROUGH

3687
02:10:48,657 --> 02:10:50,392
TRANSDUCTION WITH CD4 BEING THE

3688
02:10:50,392 --> 02:10:53,696
TARGETING MOLECULE, AND JIM

3689
02:10:53,696 --> 02:10:55,231
FOUND IN PRELIMINARY STUDIES

3690
02:10:55,231 --> 02:10:57,766
THAT TWO SIGNALING DOMAINS

3691
02:10:57,766 --> 02:11:03,439
NECESSARY FOR 1BB AND CD28, AND

3692
02:11:03,439 --> 02:11:08,043
ANIMALS UNINFECTED WERE INJECTED

3693
02:11:08,043 --> 02:11:12,014
WITH 200 MILLION ENGINEERED

3694
02:11:12,014 --> 02:11:12,748
CELLS.

3695
02:11:12,748 --> 02:11:14,517
THE RESULT WAS SOMEWHAT

3696
02:11:14,517 --> 02:11:14,850
DISAPPOINTING.

3697
02:11:14,850 --> 02:11:18,821
THERE WAS A VACCINE GIVEN TO TRY

3698
02:11:18,821 --> 02:11:22,658
TO BOOST PROLIFERATION EXPANSION

3699
02:11:22,658 --> 02:11:27,696
OF HIV-SPECIFIC CA CAR-T CELLS.

3700
02:11:27,696 --> 02:11:31,467
THE T-CELLS WERE IB FUSED AND ID

3701
02:11:31,467 --> 02:11:33,435
NOT PERSIST VERY LONG, AFTER

3702
02:11:33,435 --> 02:11:35,171
INFUSION AND WITH VACCINATION

3703
02:11:35,171 --> 02:11:37,039
DID NOT SEE AN INCREASE.

3704
02:11:37,039 --> 02:11:38,607
THE VACCINE WAS BIOACTIVE,

3705
02:11:38,607 --> 02:11:40,442
MEANING THAT IT INDUCED ANTIBODY

3706
02:11:40,442 --> 02:11:45,147
RESPONSES.

3707
02:11:45,147 --> 02:11:46,415
AND THE REASON FOR THIS IS

3708
02:11:46,415 --> 02:11:48,150
PRETTY CLEAR, THAT THE MACAQUE

3709
02:11:48,150 --> 02:11:51,086
GENERATED ANTIBODIES TO THE

3710
02:11:51,086 --> 02:11:55,891
HUMAN CD4 MOLECULE, AND AS YOU

3711
02:11:55,891 --> 02:11:57,459
CAN SEE HERE, THAT DEVELOPED IN

3712
02:11:57,459 --> 02:12:00,763
ASSOCIATION WITH CLEARANCE OF

3713
02:12:00,763 --> 02:12:03,799
THE ENGINEERED CAR-T CELLS

3714
02:12:03,799 --> 02:12:05,267
EXPRESSING HUMAN CD4.

3715
02:12:05,267 --> 02:12:07,002
SO THE NEXT STEP IS TO CLEARLY

3716
02:12:07,002 --> 02:12:10,739
SWITCH TO A RHESUS-BASED

3717
02:12:10,739 --> 02:12:12,074
CD4 CAR-T-CELL.

3718
02:12:12,074 --> 02:12:15,878
NEXT IS SOME REALLY INO INNOVATE

3719
02:12:15,878 --> 02:12:20,950
WORK DONE BY WEI LEI AND PAULA

3720
02:12:20,950 --> 02:12:23,452
CANNON TO EXPRESS BROADLY

3721
02:12:23,452 --> 02:12:25,221
NEUTRALIZING HEAVY CHAIN

3722
02:12:25,221 --> 02:12:25,788
ANTIBODIES.

3723
02:12:25,788 --> 02:12:28,524
HERE ARE THE ANTIBODIES THAT

3724
02:12:28,524 --> 02:12:34,730
WERE CREATED BY WEI LI TO MEET

3725
02:12:34,730 --> 02:12:37,533
THE CRITERIA OF HEAVY CHAIN

3726
02:12:37,533 --> 02:12:39,602
ANTIBODY OR SINGLE CHAIN FV IN

3727
02:12:39,602 --> 02:12:44,073
THE CASE OF PGT121, AND THEN

3728
02:12:44,073 --> 02:12:51,447
HUMANIZE J3 VHH AND CD4-MD1.22,

3729
02:12:51,447 --> 02:12:53,849
WHICH IS SINGLE DOMAIN CD4.

3730
02:12:53,849 --> 02:12:58,254
THEY RETAINED THEIR NEUTRALIZING

3731
02:12:58,254 --> 02:13:01,557
POTENCY, AND PAULA, THROUGH VERY

3732
02:13:01,557 --> 02:13:03,959
CLEVER DESIGN, INTRODUCED THE

3733
02:13:03,959 --> 02:13:09,965
DOMAIN INTO THE IGG 1 LOCUS, AND

3734
02:13:09,965 --> 02:13:15,037
BASICALLY SHOWS THAT YOU CAN GET

3735
02:13:15,037 --> 02:13:15,804
EFFICIENT TRANSDUCTION AND

3736
02:13:15,804 --> 02:13:18,641
EXPRESSION OF ANTIBO DEA THAT IS

3737
02:13:18,641 --> 02:13:21,810
NEUTRALIZING FROM HUMAN B CELLS

3738
02:13:21,810 --> 02:13:23,078
AND HAS NOW DONE THAT IN RHESUS

3739
02:13:23,078 --> 02:13:26,915
B CELLS, SO WE'RE RAPIDLY

3740
02:13:26,915 --> 02:13:29,618
APPROACHING THE TEST OF

3741
02:13:29,618 --> 02:13:32,388
TRANSDUCING CELLS EX VIVO,

3742
02:13:32,388 --> 02:13:34,156
RHESUS B CELLS, AND INFUSING

3743
02:13:34,156 --> 02:13:39,161
THEM INTO MACAQUES, BOOSTING

3744
02:13:39,161 --> 02:13:41,930
WITH TWO FORMS OF VACCINE TO SEE

3745
02:13:41,930 --> 02:13:44,566
IF WE CAN EXPAND B CELLS TO

3746
02:13:44,566 --> 02:13:46,635
PRODUCE THESE NEUTRALIZING HEAVY

3747
02:13:46,635 --> 02:13:50,205
CHAIN DOMAIN ANTIBODIES.

3748
02:13:50,205 --> 02:13:55,210
AND THAT STUDY IS JUST STARTING.

3749
02:13:55,210 --> 02:13:59,948
AND LASTLY, MARYANN CHECKLEY AND

3750
02:13:59,948 --> 02:14:02,284
JOHN CARNE ARE PIONEERING

3751
02:14:02,284 --> 02:14:07,623
EXPANDED NK CELLS USING A CELL

3752
02:14:07,623 --> 02:14:09,658
LINE THAT EXPRESSES

3753
02:14:09,658 --> 02:14:12,828
MEMBRANE-BOUND IL21.

3754
02:14:12,828 --> 02:14:15,564
MARY ANN IS HERE, SHE HAS A

3755
02:14:15,564 --> 02:14:16,699
POSTER, ALL THE OTHER

3756
02:14:16,699 --> 02:14:17,299
INVESTIGATORS I MENTIONED ARE

3757
02:14:17,299 --> 02:14:17,566
HERE.

3758
02:14:17,566 --> 02:14:19,201
I DON'T NEED TO TELL YOU THAT NK

3759
02:14:19,201 --> 02:14:22,438
CELLS COULD HAVE A ROLE IN

3760
02:14:22,438 --> 02:14:25,741
KILLING, RECOGNIZING KILLING

3761
02:14:25,741 --> 02:14:28,677
WITHOUT A ANTIBODY HIV INFECTED

3762
02:14:28,677 --> 02:14:32,848
CELLS BY EXPRESSION OF STRESS

3763
02:14:32,848 --> 02:14:35,150
LIGANDS ON THE INFECTED CELLS,

3764
02:14:35,150 --> 02:14:39,521
AND ALSO THE POTENTIAL FOR MORE

3765
02:14:39,521 --> 02:14:41,457
EFFICIENT KILLING WITH THE USE

3766
02:14:41,457 --> 02:14:45,594
OF A DIRECTED MONOCLONAL.

3767
02:14:45,594 --> 02:14:47,896
AND MARY ANN HAS REALLY DONE A

3768
02:14:47,896 --> 02:14:51,100
BEAUTIFUL JOB EXPANDING MK CELLS

3769
02:14:51,100 --> 02:14:54,169
WITH THIS CO-CULTURE, AND THE

3770
02:14:54,169 --> 02:14:56,472
FOLD INCREASE IS REALLY

3771
02:14:56,472 --> 02:14:57,473
REMARKABLE.

3772
02:14:57,473 --> 02:14:59,241
25,000 FOLD INCREASE IN CELLS,

3773
02:14:59,241 --> 02:15:01,310
AND YOU CAN SEE BY THE PIE CHART

3774
02:15:01,310 --> 02:15:03,379
ON THE FAR RIGHT, THE MAJORITY

3775
02:15:03,379 --> 02:15:09,585
ARE CD56 17 POSITIVE.

3776
02:15:09,585 --> 02:15:14,390
AND THESE CELLS IN THE

3777
02:15:14,390 --> 02:15:16,024
LABORATORY REDUCE VIRUS RELEASE

3778
02:15:16,024 --> 02:15:20,529
FROM INFECTED CELLS, AND REDUCE

3779
02:15:20,529 --> 02:15:22,931
INFECTED CELL NUMBER CARRYING

3780
02:15:22,931 --> 02:15:27,636
INTACT PRO VIRUSES.

3781
02:15:27,636 --> 02:15:32,708
AND REDUCE MRNA IN THOSE CELLS.

3782
02:15:32,708 --> 02:15:34,576
SO THEY'RE ACTIVE EX VIVO, THE

3783
02:15:34,576 --> 02:15:36,678
QUESTION IS, DO THEY HAVE ANY

3784
02:15:36,678 --> 02:15:39,615
EFFECT IN VIVO, AND WE HAVE AN

3785
02:15:39,615 --> 02:15:43,452
EXPERIMENT THAT HAS STARTED WITH

3786
02:15:43,452 --> 02:15:45,421
EXPANSION OF THESE CELLS, AND

3787
02:15:45,421 --> 02:15:48,757
THEY'LL BE INFUSED INTO ACUTELY

3788
02:15:48,757 --> 02:15:54,897
INFECTED MACAQUES VERSUS CONTROL

3789
02:15:54,897 --> 02:15:56,298
WITHOUT EXPANDED NKs AND WE'LL

3790
02:15:56,298 --> 02:15:58,066
SEE IF THEY HAVE EFFECT ON

3791
02:15:58,066 --> 02:15:59,601
INITIAL CONTROL OF VIREMIA.

3792
02:15:59,601 --> 02:16:01,136
WITH THAT, I'M GOING TO PASS IT

3793
02:16:01,136 --> 02:16:05,841
OVER TO DR. BAROUCH FOR RF 3.

3794
02:16:05,841 --> 02:16:14,216
[APPLAUSE]

3795
02:16:14,216 --> 02:16:18,020
>> OH IN RF 3, THEN, THE

3796
02:16:18,020 --> 02:16:19,455
NONTECHNICAL SUMMARY, THE

3797
02:16:19,455 --> 02:16:20,456
QUESTION WE'RE TRYING TO ADDRESS

3798
02:16:20,456 --> 02:16:23,091
IS, CAN WE COMBINE IMMUNE-BASED

3799
02:16:23,091 --> 02:16:25,294
STRATEGIES FOR HIV CURE, AND IS

3800
02:16:25,294 --> 02:16:28,397
IT POSSIBLE TO SHOW THAT A

3801
02:16:28,397 --> 02:16:29,465
COMBINED APPROACH MIGHT BE

3802
02:16:29,465 --> 02:16:30,466
BETTER THAN INDIVIDUAL

3803
02:16:30,466 --> 02:16:31,467
STRATEGIES ALONE.

3804
02:16:31,467 --> 02:16:33,268
IT'S BOTH A CONCEPTUAL QUESTION

3805
02:16:33,268 --> 02:16:35,737
AS WELL AS A PRACTICAL QUESTION

3806
02:16:35,737 --> 02:16:36,939
FOR SPECIFIC INTERVENTIONS.

3807
02:16:36,939 --> 02:16:39,842
SO WHY IS THIS WORK IMPORTANT

3808
02:16:39,842 --> 02:16:41,343
FOR CURE OR CONTROL?

3809
02:16:41,343 --> 02:16:42,778
WE THINK IT'S IMPORTANT BECAUSE

3810
02:16:42,778 --> 02:16:45,080
IF TWO OR MORE PARTIALLY

3811
02:16:45,080 --> 02:16:47,049
EFFECTIVE CURE STRATEGIES CAN BE

3812
02:16:47,049 --> 02:16:48,083
COMBINED, WE MIGHT BE ABLE TO

3813
02:16:48,083 --> 02:16:51,153
HAVE A GREATER CHANCE OF

3814
02:16:51,153 --> 02:16:53,222
DEVELOPMENT OF CLINICALLY

3815
02:16:53,222 --> 02:16:54,323
MEANINGFUL HIV CURE, SO WHY

3816
02:16:54,323 --> 02:16:56,024
SHOULD COMMUNITY BE EXCITED

3817
02:16:56,024 --> 02:16:56,992
ABOUT THE RESULTS AND PROGRESS

3818
02:16:56,992 --> 02:16:57,526
PRESENTED?

3819
02:16:57,526 --> 02:17:01,063
SO WE'LL SHOW DATA THAT IN

3820
02:17:01,063 --> 02:17:02,931
MACAQUES, THE COMBINATION OF

3821
02:17:02,931 --> 02:17:04,800
THERAPEUTIC VACCINES AND BROADLY

3822
02:17:04,800 --> 02:17:05,567
NEUTRALIZING ANTIBODIES RESULTS

3823
02:17:05,567 --> 02:17:07,135
IN MORE ANIMALS ACHIEVING

3824
02:17:07,135 --> 02:17:08,437
DURABLE VIROLOGIC CONTROL THAN

3825
02:17:08,437 --> 02:17:10,405
EITHER APPROACH ALONE FOLLOWING

3826
02:17:10,405 --> 02:17:12,040
ART DISCONTINUATION.

3827
02:17:12,040 --> 02:17:13,408
WE'RE ALSO PERFORMING PILOT

3828
02:17:13,408 --> 02:17:14,943
STUDIES WITH INNOVATIVE

3829
02:17:14,943 --> 02:17:15,911
CELL-BASED CONCEPTS THAT COULD

3830
02:17:15,911 --> 02:17:18,480
BE COMBINED WITH ONE OR OTHER OF

3831
02:17:18,480 --> 02:17:20,883
THESE IMMUNOLOGIC INTERVENTIONS

3832
02:17:20,883 --> 02:17:21,450
SHOULD THEY WORK.

3833
02:17:21,450 --> 02:17:23,051
SO IN FOCUS THREE, IN TERMS OF

3834
02:17:23,051 --> 02:17:24,753
THINKING ABOUT VIRUS

3835
02:17:24,753 --> 02:17:25,621
ERADICATION, OF COURSE IT'S A

3836
02:17:25,621 --> 02:17:30,893
VERY HIGH BAR, BUT OUR CONCEPT

3837
02:17:30,893 --> 02:17:33,328
IS TO ADOPT THE CLINICAL

3838
02:17:33,328 --> 02:17:35,831
STRATEGY FOR LEUKEMIA.

3839
02:17:35,831 --> 02:17:37,199
IN OTHER WORDS, INDUCTION

3840
02:17:37,199 --> 02:17:39,334
THERAPY FOLLOWED BY

3841
02:17:39,334 --> 02:17:40,702
CONSOLIDATION THERAPY, WITH THE

3842
02:17:40,702 --> 02:17:42,337
MODEST GOAL OR MODEST

3843
02:17:42,337 --> 02:17:43,772
RECOGNITION THAT IT IS

3844
02:17:43,772 --> 02:17:46,041
EXCEEDINGLY UNLIKELY THAT ANY

3845
02:17:46,041 --> 02:17:47,976
APPROACH THAT WE KNOW OF SHORT

3846
02:17:47,976 --> 02:17:49,077
OF BONE MARROW TRANSPLANTATION

3847
02:17:49,077 --> 02:17:51,880
WOULD TRULY ERADICATE THE ENTIRE

3848
02:17:51,880 --> 02:17:53,715
VIRAL RESERVOIR.

3849
02:17:53,715 --> 02:17:54,917
BUT WE THINK THAT THERE MIGHT BE

3850
02:17:54,917 --> 02:17:57,519
A WAY OF INDUCTION THERAPY FOR

3851
02:17:57,519 --> 02:18:00,022
THE RAPID ELIMINATION FOR AT

3852
02:18:00,022 --> 02:18:02,624
LEAST THE MAJORITY OF THE VIRAL

3853
02:18:02,624 --> 02:18:05,127
RES VOR WITH STRATEGIES SUCH AS

3854
02:18:05,127 --> 02:18:06,895
COMBINATION OF B NABS WITH

3855
02:18:06,895 --> 02:18:08,130
IMMUNE ACTIVATORS, COMBINATION

3856
02:18:08,130 --> 02:18:10,098
OF ENHANCED NK CELLS WITH OR

3857
02:18:10,098 --> 02:18:13,802
WITHOUT B NABS AND CAR-T CELLS

3858
02:18:13,802 --> 02:18:15,837
THAT WOULD TARGET MOLECULES LIKE

3859
02:18:15,837 --> 02:18:16,138
CCR5.

3860
02:18:16,138 --> 02:18:17,506
BUT THAT WOULD CERTAINLY NEED

3861
02:18:17,506 --> 02:18:19,641
SOME FORM OF ADDITIONAL

3862
02:18:19,641 --> 02:18:20,442
CONSOLIDATION THERAPY WHICH

3863
02:18:20,442 --> 02:18:21,777
ESSENTIALLY WOULD BE

3864
02:18:21,777 --> 02:18:23,545
IMMUNOSURVEILLANCE TO ELIMINATE

3865
02:18:23,545 --> 02:18:25,113
THE RESIDUAL VIRAL RESERVOIR,

3866
02:18:25,113 --> 02:18:27,049
SUCH AS THE USE OF THERAPEUTIC

3867
02:18:27,049 --> 02:18:29,017
VACCINE, ENGINEERED B CELLS OR

3868
02:18:29,017 --> 02:18:30,886
CAR-T CELLS TARGETING ENVELOPE

3869
02:18:30,886 --> 02:18:32,287
AND WE THINK PERHAPS A

3870
02:18:32,287 --> 02:18:33,322
COMBINATION OF THESE APPROACHES

3871
02:18:33,322 --> 02:18:35,424
MIGHT BE ABLE TO ACHIEVE VIRUS

3872
02:18:35,424 --> 02:18:37,092
ERADICATION OR AT LEAST MAKE

3873
02:18:37,092 --> 02:18:37,659
PROGRESS TOWARDS THAT LOFTY

3874
02:18:37,659 --> 02:18:39,394
GOAL.

3875
02:18:39,394 --> 02:18:41,930
SO WE STARTED INVESTIGATING

3876
02:18:41,930 --> 02:18:43,265
THERAPEUTIC VACCINES A NUMBER OF

3877
02:18:43,265 --> 02:18:43,532
YEARS AGO.

3878
02:18:43,532 --> 02:18:44,933
THIS WAS ACTUALLY IN THE CONTEXT

3879
02:18:44,933 --> 02:18:48,036
OF I4C 1.0, AND IN 2016, WE

3880
02:18:48,036 --> 02:18:49,237
PUBLISHED A STUDY IN WHICH WE

3881
02:18:49,237 --> 02:18:50,639
DEMONSTRATED THAT THE

3882
02:18:50,639 --> 02:18:53,075
THERAPEUTIC VACCINE WITH VECTORS

3883
02:18:53,075 --> 02:18:57,379
AT 26MVA TOGETHER WITH A

3884
02:18:57,379 --> 02:18:58,347
TLR7 AGONIST IN COLLABORATION

3885
02:18:58,347 --> 02:19:02,284
WITH GILEAD WAS ABLE TO LEAD TO

3886
02:19:02,284 --> 02:19:04,620
PARTIAL VIROLOGIC CONTROL

3887
02:19:04,620 --> 02:19:05,954
FOLLOWING ART DISCONTINUATION.

3888
02:19:05,954 --> 02:19:07,456
HERE YOU SATISFY ON THE LEFT

3889
02:19:07,456 --> 02:19:13,228
SEE ON THE LEFT ASUBSTANTIAL --E

3890
02:19:13,228 --> 02:19:17,399
MAGNITUDE AND THAT RESULTED IN

3891
02:19:17,399 --> 02:19:18,300
SUBSTANTIAL REDUCTION OF VIRAL

3892
02:19:18,300 --> 02:19:20,202
LOADS IN THE COMBINATION VAC

3893
02:19:20,202 --> 02:19:23,805
SEES PLUS VESATOLIMOD GROUP.

3894
02:19:23,805 --> 02:19:24,940
NOT SHOWN HERE WE ALSO

3895
02:19:24,940 --> 02:19:26,141
DEMONSTRATED A SUBSET OF THE

3896
02:19:26,141 --> 02:19:28,577
ANIMALS, IT WAS 3 OUT OF 12,

3897
02:19:28,577 --> 02:19:32,681
ACTUALLY HAD POST REBOND

3898
02:19:32,681 --> 02:19:34,549
VIROLOGIC CONTROLS TO

3899
02:19:34,549 --> 02:19:35,317
UNDETECTABLE LEVELS.

3900
02:19:35,317 --> 02:19:36,818
THE VACCINE APPEARED TO HAVE THE

3901
02:19:36,818 --> 02:19:38,286
PHENOTYPE OF POST REBOUND

3902
02:19:38,286 --> 02:19:42,991
VIROLOGIC CONTROL.

3903
02:19:42,991 --> 02:19:44,426
THIS WAS THEN TRANSLATED INTO

3904
02:19:44,426 --> 02:19:47,262
HUMANS WITH THE SAME VACCINE IN

3905
02:19:47,262 --> 02:19:50,932
HUMANS LED BY THE MHRP GROUP IN

3906
02:19:50,932 --> 02:19:52,367
THAILAND AND THE VACCINE

3907
02:19:52,367 --> 02:19:56,405
SIMILARLY WAS HIGHLY IMMUNOGENIC

3908
02:19:56,405 --> 02:19:59,374
IN EARLY ART -- OR EARLY

3909
02:19:59,374 --> 02:20:01,209
ART-TREATED HUMANS IN THAILAND

3910
02:20:01,209 --> 02:20:03,945
SHOWN AT THE BOTTOM.

3911
02:20:03,945 --> 02:20:05,380
THEN FOLLOWING A TREATMENT

3912
02:20:05,380 --> 02:20:07,716
INTERRUPTION, THEN THE VACCINE

3913
02:20:07,716 --> 02:20:10,552
LED TO A MODEST DELAY IN VIRAL

3914
02:20:10,552 --> 02:20:12,087
REBOUND THAT WAS A TREND IN THE

3915
02:20:12,087 --> 02:20:15,057
TOTAL COHORT AND WAS SIGNIFICANT

3916
02:20:15,057 --> 02:20:16,958
IF ONE CONTROLLER IN THE

3917
02:20:16,958 --> 02:20:19,695
PLACEBO -- ONE HLA FAVORABLE

3918
02:20:19,695 --> 02:20:22,698
ALLELE INDIVIDUAL IS POST HOC

3919
02:20:22,698 --> 02:20:24,032
EXCLUDED SO AT LEAST A TREND IN

3920
02:20:24,032 --> 02:20:30,338
THE RIGHT DIRECTION.

3921
02:20:30,338 --> 02:20:35,110
WE PUBLISHED A STUDY O ANTIBODIS

3922
02:20:35,110 --> 02:20:38,580
IN THE MACAQUE MODEL.

3923
02:20:38,580 --> 02:20:41,817
PG121 AGAIN WITH THE TLR AGONIST

3924
02:20:41,817 --> 02:20:43,118
RESULTED IN SUBSTANTIAL DELAY OF

3925
02:20:43,118 --> 02:20:44,453
VIRAL REBOUND FOLLOWING ART

3926
02:20:44,453 --> 02:20:44,820
DISCONTINUATION.

3927
02:20:44,820 --> 02:20:47,956
YOU SEE THE CURVE ON THE LEFT

3928
02:20:47,956 --> 02:20:50,625
DEMONSTRATING THAT

3929
02:20:50,625 --> 02:20:51,226
PD2121 PARTICULARLY WHEN GIVEN

3930
02:20:51,226 --> 02:20:53,562
WITH THE IMMUNE STIMULATOR

3931
02:20:53,562 --> 02:20:56,231
RESULTED IN A DELAY OF VIRAL

3932
02:20:56,231 --> 02:20:59,201
REBOUND, AND IN FACT, PREVENTION

3933
02:20:59,201 --> 02:21:02,237
OF REBOUND IN THE SUBSET OF THE

3934
02:21:02,237 --> 02:21:06,241
ANIMALS.

3935
02:21:06,241 --> 02:21:07,509
THESE BNABS HAVE ALSO BEEN

3936
02:21:07,509 --> 02:21:10,345
TRANSLATED TO THE CLINIC.

3937
02:21:10,345 --> 02:21:15,584
OUR GROUP HAVE MOVED THE

3938
02:21:15,584 --> 02:21:16,852
PGT121 TO FIRST IN HUMAN STUDIES

3939
02:21:16,852 --> 02:21:18,920
AS WELL AS OTHER ANTIBODIES, AND

3940
02:21:18,920 --> 02:21:24,059
WE SHOWED IN VIREMIC PERSONS

3941
02:21:24,059 --> 02:21:26,061
LIVING WITH HIV WITH SENSITIVE

3942
02:21:26,061 --> 02:21:28,363
VIRUS THAT WE SAW ABOUT A TWO TO

3943
02:21:28,363 --> 02:21:30,065
2 1/2 LOG DROP IN VIRAL LOADS

3944
02:21:30,065 --> 02:21:32,901
WITH A SINGLE INFUSION OF THIS

3945
02:21:32,901 --> 02:21:34,002
MONOCLONAL ANTIBODY.

3946
02:21:34,002 --> 02:21:35,303
NOT SURPRISINGLY, THIS WAS NOT

3947
02:21:35,303 --> 02:21:36,505
SEEN IN INDIVIDUALS WITH

3948
02:21:36,505 --> 02:21:38,740
RESISTANT VIRUS, AND WE MADE THE

3949
02:21:38,740 --> 02:21:40,275
CURIOUS OBSERVATION THAT PEOPLE

3950
02:21:40,275 --> 02:21:41,610
THAT NATURALLY HAD A VERY LOW

3951
02:21:41,610 --> 02:21:44,146
LEVEL OF VIRUS IN THE RIGHT

3952
02:21:44,146 --> 02:21:47,415
PANEL ACTUALLY HAD IN SOME CASES

3953
02:21:47,415 --> 02:21:50,819
LONG-TERM VIROLOGIC CONTROL

3954
02:21:50,819 --> 02:21:52,854
AFTER BNAB INFUSION THAT VASTLY

3955
02:21:52,854 --> 02:21:54,156
EXCEEDED THE HALF-LIFE OF THE

3956
02:21:54,156 --> 02:21:55,123
ANTIBODY.

3957
02:21:55,123 --> 02:21:58,026
NOW, I SHOULD CLARIFY THAT WE DO

3958
02:21:58,026 --> 02:22:00,662
NOT BELIEVE THIS IS A VACCINAL

3959
02:22:00,662 --> 02:22:02,931
EFFECT BECAUSE THE T-CELL

3960
02:22:02,931 --> 02:22:04,132
RESPONSES, MAGNITUDE, BREADTH,

3961
02:22:04,132 --> 02:22:05,734
FUNCTION, ANY WAY WE LOOK AT IT,

3962
02:22:05,734 --> 02:22:07,035
WERE UNCHANGED BY THE BNAB

3963
02:22:07,035 --> 02:22:07,402
ADMINISTRATION.

3964
02:22:07,402 --> 02:22:09,337
SO THERE IS IN SOME CASES LONG

3965
02:22:09,337 --> 02:22:10,539
TERM VIROLOGIC CONTROL AS A

3966
02:22:10,539 --> 02:22:12,040
RESULT OF BNAB ADMINISTRATION,

3967
02:22:12,040 --> 02:22:14,209
HOWEVER, IN OUR HANDS AND

3968
02:22:14,209 --> 02:22:15,644
MONKEYS AND HUMANS, IT IS NOT

3969
02:22:15,644 --> 02:22:18,980
DUE TO A VACCINAL EFFECT.

3970
02:22:18,980 --> 02:22:23,218
A STUDY THAT HAS RECENTLY BEEN

3971
02:22:23,218 --> 02:22:25,654
PUBLISHED THAT VICTORIA WALKER

3972
02:22:25,654 --> 02:22:27,222
SPERLING HAS A POSTER ON IT I

3973
02:22:27,222 --> 02:22:28,323
WOULD ENCOURAGE YOU TO SEE THAT

3974
02:22:28,323 --> 02:22:30,292
FOR MORE DETAILS IS TO LOOK AT

3975
02:22:30,292 --> 02:22:36,264
COMBINATION THERAPY WITH

3976
02:22:36,264 --> 02:22:39,334
ADD26/MVA VACCINATION IN

3977
02:22:39,334 --> 02:22:40,735
PGT121 IN SHIV INFECTED RHESUS

3978
02:22:40,735 --> 02:22:41,536
MACAQUES.

3979
02:22:41,536 --> 02:22:43,205
IT REALLY IS A CONCEPT OF

3980
02:22:43,205 --> 02:22:44,072
COMBINATION THERAPY AND IS IT

3981
02:22:44,072 --> 02:22:47,742
POSSIBLE TO SEE AN ADDITIVE,

3982
02:22:47,742 --> 02:22:49,177
SYNERGISTIC, OR ANTAGONISTIC

3983
02:22:49,177 --> 02:22:49,477
COMBINATION.

3984
02:22:49,477 --> 02:22:51,580
SO IN THIS STUDY, 51 RHESUS

3985
02:22:51,580 --> 02:22:54,482
MACAQUES WERE CHALLENGED

3986
02:22:54,482 --> 02:22:56,218
INTRARECTALLY AND TREATED

3987
02:22:56,218 --> 02:22:58,086
STARTING ON DAY 9, SO EARLY WITH

3988
02:22:58,086 --> 02:22:59,487
PREFORMULATED ART COMBINATION IN

3989
02:22:59,487 --> 02:23:02,023
COLLABORATION WITH GILEAD, AT

3990
02:23:02,023 --> 02:23:09,164
THE NOV --GROUP ONE INVOLVED THY

3991
02:23:09,164 --> 02:23:10,098
WITH VESATOLIMOD.

3992
02:23:10,098 --> 02:23:11,967
GROUP TWO WAS ONLY THE VACCINE,

3993
02:23:11,967 --> 02:23:12,968
GROUP THREE WAS ONLY THE

3994
02:23:12,968 --> 02:23:14,970
ANTIBODY AND GROUP FOUR WAS A

3995
02:23:14,970 --> 02:23:15,303
SHAM GROUP.

3996
02:23:15,303 --> 02:23:17,806
WE DO BELIEVE A GROUP OF AT

3997
02:23:17,806 --> 02:23:19,474
LEAST 12 MACAQUES ARE NEEDED FOR

3998
02:23:19,474 --> 02:23:20,008
ADD QA POWER.

3999
02:23:20,008 --> 02:23:21,910
YOU CAN SEE THE SCHEME OF THE

4000
02:23:21,910 --> 02:23:23,345
STUDY, BASICALLY IT'S FOUR SHOTS

4001
02:23:23,345 --> 02:23:26,481
OF VACCINATION AND/OR FIVE

4002
02:23:26,481 --> 02:23:28,984
INFUSIONS OF THE ANTIBODY WITH

4003
02:23:28,984 --> 02:23:29,951
VESATOLIMOD INTERSPERSED EVERY

4004
02:23:29,951 --> 02:23:31,152
TWO WEEKS IN THE LATTER PART OF

4005
02:23:31,152 --> 02:23:34,322
THE INTERVENTION SIGH KE. SO

4006
02:23:34,322 --> 02:23:35,891
CLEARLY NOT A CLINICALLY

4007
02:23:35,891 --> 02:23:36,925
FRIENDLY REGIMEN.

4008
02:23:36,925 --> 02:23:38,860
WE WOULD LOVE TO HAVE A ONE-SHOT

4009
02:23:38,860 --> 02:23:39,961
CURE BUT THIS WAS A PROOF OF

4010
02:23:39,961 --> 02:23:44,633
CONCEPT STUDY.

4011
02:23:44,633 --> 02:23:47,903
AFTER SHIV INFECTION, ALL THE

4012
02:23:47,903 --> 02:23:55,377
ANIMALS BECAME HIGH L HIGHLY VIE

4013
02:23:55,377 --> 02:23:56,811
REMEMO, NO EVIDENCE OF BLIPPING

4014
02:23:56,811 --> 02:23:59,014
FOR THE ENTIRE ART SUPPRESSION

4015
02:23:59,014 --> 02:24:02,350
AND INTERVENTION PERIOD.

4016
02:24:02,350 --> 02:24:04,653
WE ALSO SHOW VESATOLIMOD LED TO

4017
02:24:04,653 --> 02:24:07,289
A SIGNIFICANT ACTIVATION OF

4018
02:24:07,289 --> 02:24:09,824
CD4 POSITIVE T-CELLS AFTER EACH

4019
02:24:09,824 --> 02:24:13,028
ADMINISTRATION.

4020
02:24:13,028 --> 02:24:14,796
FOR THE MON CLONL ANTIBODY WE

4021
02:24:14,796 --> 02:24:15,764
SHOWED VERY GOOD PK IN THE

4022
02:24:15,764 --> 02:24:17,332
ANIMALS AFTER EACH OF THE FIVE

4023
02:24:17,332 --> 02:24:20,635
INFUSIONS WITH THE EXPECTED

4024
02:24:20,635 --> 02:24:21,836
JAGGED SAWTOOTH PATTERN AND

4025
02:24:21,836 --> 02:24:22,604
THAT'S NOT SHOWN HERE.

4026
02:24:22,604 --> 02:24:23,972
FOR THE GROUPS THAT DID RECEIVE

4027
02:24:23,972 --> 02:24:26,007
THE VACCINE, WE OBSERVED A

4028
02:24:26,007 --> 02:24:26,908
MASSIVE INCREASE IN THE

4029
02:24:26,908 --> 02:24:30,879
MAGNITUDE AND BREADTH OF C8 AND

4030
02:24:30,879 --> 02:24:33,949
CD4 T-CELL RESPONSES WITH

4031
02:24:33,949 --> 02:24:35,483
PARALLEL ICS DATA IN THE MANUAL

4032
02:24:35,483 --> 02:24:37,218
SCRIPT ESSENTIALLY SHOWING A

4033
02:24:37,218 --> 02:24:39,521
MASSIVE INCREASE IN CELLULAR

4034
02:24:39,521 --> 02:24:47,729
RESPONSES FOLLOWING BOTH THE AD

4035
02:24:47,729 --> 02:24:49,230
PRIMING AS WELL AS BOOSTING

4036
02:24:49,230 --> 02:24:49,698
COMPONENT.

4037
02:24:49,698 --> 02:24:50,832
THIS IS SHOWN IN THE MAGNITUDE

4038
02:24:50,832 --> 02:24:52,167
OF RESPONSES AS WELL AS A MAJOR

4039
02:24:52,167 --> 02:24:53,368
INCREASE IN THE NUMBER OF

4040
02:24:53,368 --> 02:24:54,602
RESPONDING SUBPOOLS WHICH IS OUR

4041
02:24:54,602 --> 02:24:57,572
SURROGATE MEASURE FOR BREADTH.

4042
02:24:57,572 --> 02:25:01,509
FOLLOWING -- SO WE FOLLOWED THE

4043
02:25:01,509 --> 02:25:02,911
ANIMALS FOR FOUR OR FIVE MONTHS

4044
02:25:02,911 --> 02:25:06,381
TO LET THE MONOCLONAL ANTIBODY

4045
02:25:06,381 --> 02:25:08,883
LEVELS DROP BELOW TO

4046
02:25:08,883 --> 02:25:09,651
UNDETECTABLE LEVEL SO IS WE

4047
02:25:09,651 --> 02:25:10,852
DON'T BELIEVE THERE WAS ANY

4048
02:25:10,852 --> 02:25:12,220
RESIDUAL ANTIBODY AT THE TIME OF

4049
02:25:12,220 --> 02:25:12,887
TREATMENT INTERRUPTION.

4050
02:25:12,887 --> 02:25:14,122
AFTER ART DISCONTINUATION THEN

4051
02:25:14,122 --> 02:25:15,523
WE LOOKED AT VIRAL REBOUND.

4052
02:25:15,523 --> 02:25:16,992
ALL THE ANIMALS IN THE SHAM

4053
02:25:16,992 --> 02:25:18,960
CONTROL GROUP REBOUNDED AND HAD

4054
02:25:18,960 --> 02:25:21,029
SET POINT VIREMIA.

4055
02:25:21,029 --> 02:25:22,697
OF IN THE ANIMALS THAT RECEIVED

4056
02:25:22,697 --> 02:25:25,233
THE VACCINE, IN THE BOTTOM LEFT,

4057
02:25:25,233 --> 02:25:26,701
ALL THE ANIMALS REBOUNDED IN A

4058
02:25:26,701 --> 02:25:27,969
VERY SIMILAR TIME COURSE, BUT

4059
02:25:27,969 --> 02:25:30,338
ABOUT A THIRD OF THEM APPEAR TO

4060
02:25:30,338 --> 02:25:32,407
HAVE POST REBOUND VIROLOGIC

4061
02:25:32,407 --> 02:25:35,543
CONTROL VERY SA SIMILAR TO OUR 6

4062
02:25:35,543 --> 02:25:37,612
PAPER AND, OVERALL AS A GROUP,

4063
02:25:37,612 --> 02:25:40,015
HAD LOWER SET POINT VIRAL LOADS.

4064
02:25:40,015 --> 02:25:41,750
IN THE ANIMALS THAT RECEIVED THE

4065
02:25:41,750 --> 02:25:42,617
ANTIBODY SHOWN IN THE UPPER

4066
02:25:42,617 --> 02:25:45,553
RIGHT, THEN THERE IS A DELAY IN

4067
02:25:45,553 --> 02:25:46,955
VIRAL REBOUND AND THERE WAS

4068
02:25:46,955 --> 02:25:47,856
SEVERAL ANIMALS THAT APPEARED

4069
02:25:47,856 --> 02:25:49,991
NOT TO REBOUND AT ALL.

4070
02:25:49,991 --> 02:25:51,192
AND IN THE COMBINATION GROUP

4071
02:25:51,192 --> 02:25:53,128
THAT RECEIVED BOTH THE ACTIVE

4072
02:25:53,128 --> 02:25:54,529
AND PASSIVE IMMUNIZATION IN THE

4073
02:25:54,529 --> 02:25:57,732
BOTTOM RIGHT, THEN WE OBSERVED

4074
02:25:57,732 --> 02:26:00,268
WHAT WE INTERPRETED AS AN

4075
02:26:00,268 --> 02:26:01,069
ADDITIVE EFFECT.

4076
02:26:01,069 --> 02:26:04,339
A LARGER NUMBER OF ANIMALS

4077
02:26:04,339 --> 02:26:06,107
REMAINED AVIE REMEMO AT THE END

4078
02:26:06,107 --> 02:26:06,541
OF THE STUDY PERIOD.

4079
02:26:06,541 --> 02:26:07,609
THIS WAS REALLY A MIXTURE OF

4080
02:26:07,609 --> 02:26:09,878
SOME ANIMALS THAT REBOUNDED AND

4081
02:26:09,878 --> 02:26:11,780
EXHIBITED POST ART VIROLOGIC

4082
02:26:11,780 --> 02:26:13,014
CONTROL, AND OTHER ANIMALS THAT

4083
02:26:13,014 --> 02:26:14,649
EXHIBITED A DELAYED REBOUND OR

4084
02:26:14,649 --> 02:26:16,117
NO REBOUND AT ALL.

4085
02:26:16,117 --> 02:26:17,986
SO IT REALLY APPEARS THAT NOW

4086
02:26:17,986 --> 02:26:20,055
WITH MULTIPLE LARGE SCALE

4087
02:26:20,055 --> 02:26:21,556
NON-HUMAN PRIMATE STUDIES, THE

4088
02:26:21,556 --> 02:26:23,625
VACCINE EFFECT IS REALLY NOT AN

4089
02:26:23,625 --> 02:26:25,293
EFFECT IN DELAYING OR PREVENTING

4090
02:26:25,293 --> 02:26:27,962
REBOUND, BUT IT REALLY APPEARS

4091
02:26:27,962 --> 02:26:30,265
TO RESULT IN POST REBOUND

4092
02:26:30,265 --> 02:26:31,699
VIROLOGIC CONTROL WHEREAS THE

4093
02:26:31,699 --> 02:26:33,368
BROADLY NEUTRALIZING ANTIBODY

4094
02:26:33,368 --> 02:26:34,903
APPEARS TO BE ABLE TO DELAY

4095
02:26:34,903 --> 02:26:38,073
REBOUND AND IN OCCASIONAL CASES,

4096
02:26:38,073 --> 02:26:39,174
PREVENT REBOUND IN CERTAIN

4097
02:26:39,174 --> 02:26:40,308
SETTINGS.

4098
02:26:40,308 --> 02:26:41,543
AND THE COMBINATION OF ACTIVE

4099
02:26:41,543 --> 02:26:42,744
AND PASSIVE IMMUNIZATION

4100
02:26:42,744 --> 02:26:44,479
RESULTED IN A MIXTURE OF THESE

4101
02:26:44,479 --> 02:26:47,282
PHENOTYPES AND THE TOTAL RESULT

4102
02:26:47,282 --> 02:26:57,826
IS THAT SEVEN OUT OF 10 ANIMALS

4103
02:26:58,827 --> 02:26:59,861
WERE AVIREMIC BY THE END OF THE

4104
02:26:59,861 --> 02:27:01,596
STUDY COMPARED WITH 5 OUT OF 12

4105
02:27:01,596 --> 02:27:03,264
AND 4 OUT OF 12 AND ZERO OUT OF

4106
02:27:03,264 --> 02:27:05,934
15 IN THE SHAM CONTROL GROUP.

4107
02:27:05,934 --> 02:27:12,006
SO THE OVERALL VIRUS IS SHOWN IN

4108
02:27:12,006 --> 02:27:16,411
THE LEFT, SHOWING THAT THE AT LT

4109
02:27:16,411 --> 02:27:17,712
ON A POINT ESTIMATE THE

4110
02:27:17,712 --> 02:27:19,614
COMBINATION GROUP HAD LOWER

4111
02:27:19,614 --> 02:27:21,716
MEDIAN VIRAL LOADS COMPARED WITH

4112
02:27:21,716 --> 02:27:23,885
THE INDIVIDUAL INTERVENTIONS AND

4113
02:27:23,885 --> 02:27:25,186
SUBSTANTIALLY LOWER THAN THE

4114
02:27:25,186 --> 02:27:26,020
SHAM CONTROL GROUP.

4115
02:27:26,020 --> 02:27:27,555
IF WE LOOK AT THE KAPLAN-MEIER

4116
02:27:27,555 --> 02:27:29,090
CURVES ON THE RIGHT FOR REBOUND,

4117
02:27:29,090 --> 02:27:30,625
THEN THE TWO GROUPS THAT RECEIVE

4118
02:27:30,625 --> 02:27:32,227
THE BROADLY NEUTRALIZING

4119
02:27:32,227 --> 02:27:33,495
ANTIBODY WERE CLEARLY THE TWO

4120
02:27:33,495 --> 02:27:36,698
GROUPS THAT SHOWED AN EFFECT ON

4121
02:27:36,698 --> 02:27:38,399
THE FRACTION OF ANIMALS THAT

4122
02:27:38,399 --> 02:27:39,601
REBOUNDED AND THE TIME FOR

4123
02:27:39,601 --> 02:27:41,035
REBOUND.

4124
02:27:41,035 --> 02:27:42,770
HOWEVER, IN TERMS OF VIROLOGIC

4125
02:27:42,770 --> 02:27:44,472
CONTROL, THERE WAS A CLEAR

4126
02:27:44,472 --> 02:27:45,240
CORRELATION WITH THE GROUPS THAT

4127
02:27:45,240 --> 02:27:49,277
RECEIVED THE VACCINE, AND THE

4128
02:27:49,277 --> 02:27:55,250
CELL MAGNITUDE AND BREADTH WAS A

4129
02:27:55,250 --> 02:28:00,088
IINVERSE LIQUOR LATED WITH VIRAL

4130
02:28:00,088 --> 02:28:02,157
LOADS AFTER ART DISCONTINUATION.

4131
02:28:02,157 --> 02:28:04,092
WE ARE EVALUATING WHETHER ART

4132
02:28:04,092 --> 02:28:05,727
PLUS BROADLY NEUTRALIZING

4133
02:28:05,727 --> 02:28:08,663
ANTIBODY THERAPY CAN BE USED IN

4134
02:28:08,663 --> 02:28:10,098
EARLY -- FOR EARLY TREATMENT OF

4135
02:28:10,098 --> 02:28:11,833
SHIV INFECTED RHESUS MACAQUES

4136
02:28:11,833 --> 02:28:16,070
AND GIVEN THE PREVIOUS RESULTS

4137
02:28:16,070 --> 02:28:19,107
WITH VESATOLIMOD SHOWING DELAY

4138
02:28:19,107 --> 02:28:20,208
OF -- WE WERE ASKING THE

4139
02:28:20,208 --> 02:28:21,176
QUESTION CAN COMBINATION THERAPY

4140
02:28:21,176 --> 02:28:23,211
AT THE TIME OF ART INITIATION

4141
02:28:23,211 --> 02:28:25,914
REDUCE RESERVOIR SEEDING, SO 36

4142
02:28:25,914 --> 02:28:30,318
MACAQUES WERE INFECTED

4143
02:28:30,318 --> 02:28:34,522
INTRARECTALLY WITH SHIV SF16

4144
02:28:34,522 --> 02:28:35,723
SF162P3 AND AT EARLY SET POINT

4145
02:28:35,723 --> 02:28:40,028
WITH EITHER ART ALONE, ART PLUS

4146
02:28:40,028 --> 02:28:45,233
PGT121, OR ART PLUS PGT121 PLUS

4147
02:28:45,233 --> 02:28:46,434
VESATOLIMOD AND THE STUDY IS

4148
02:28:46,434 --> 02:28:47,302
STILL IN PROGRESS.

4149
02:28:47,302 --> 02:28:51,306
FUTURE PLANS FOR THE I4C

4150
02:28:51,306 --> 02:28:53,408
2.0 OVERALL IS TO IMPROPER OUR

4151
02:28:53,408 --> 02:28:54,709
BASIC UNDERSTANDING OF THE VIRAL

4152
02:28:54,709 --> 02:28:56,811
RESERVOIR AND CORRELATES OF

4153
02:28:56,811 --> 02:28:58,846
REBOUND IN PRIMATES AND HUMANS,

4154
02:28:58,846 --> 02:29:02,784
TOO EVALUATE THERAPEUTICS AND

4155
02:29:02,784 --> 02:29:07,021
VACCINES -- AND WE'RE ALSO DOING

4156
02:29:07,021 --> 02:29:08,656
AS YOU HEARD A SERIES OF PILOT

4157
02:29:08,656 --> 02:29:10,925
STUDIES ON CELL-BASED APPROACHES

4158
02:29:10,925 --> 02:29:11,759
INCLUDING CAR-T CELLS ENGINEERED

4159
02:29:11,759 --> 02:29:13,528
B CELLS AND ENHANCED NK CELLS

4160
02:29:13,528 --> 02:29:15,396
AND BASED ON THE RESULTS OF ALL

4161
02:29:15,396 --> 02:29:16,998
OF THESE ONGOING STUDIES WE PLAN

4162
02:29:16,998 --> 02:29:18,366
TO DESIGN IN THE SECOND HALF OF

4163
02:29:18,366 --> 02:29:20,201
THE GRANT NEXT GENERATION

4164
02:29:20,201 --> 02:29:22,337
COMBINED IMMUNOTHERAPY STUDIES.

4165
02:29:22,337 --> 02:29:23,972
AND WITH THAT, I'LL TURN IT OVER

4166
02:29:23,972 --> 02:29:25,840
TO JESSICA FOR COMMUNITY

4167
02:29:25,840 --> 02:29:26,140
ENGAGEMENT.

4168
02:29:26,140 --> 02:29:32,847
[APPLAUSE]

4169
02:29:32,847 --> 02:29:34,082
>> HELLO AGAIN.

4170
02:29:34,082 --> 02:29:36,384
SO I'M GOING TO TALK ABOUT OUR

4171
02:29:36,384 --> 02:29:37,485
PROGRAM IN I4C.

4172
02:29:37,485 --> 02:29:39,621
SO WE DO HAVE THREE MAIN GOALS

4173
02:29:39,621 --> 02:29:41,723
HERE, AGAIN IT'S TO REALLY BUILD

4174
02:29:41,723 --> 02:29:43,057
THAT NETWORK OF CIVIL SOCIETY

4175
02:29:43,057 --> 02:29:45,560
AND COMMUNITY THAT CAN SPEAK IN

4176
02:29:45,560 --> 02:29:46,127
MEANINGFULLY ENGAGE IN THIS

4177
02:29:46,127 --> 02:29:46,327
WORK.

4178
02:29:46,327 --> 02:29:47,729
WE REALLY WANT TO HAVE DIRECT

4179
02:29:47,729 --> 02:29:49,464
FEEDBACK INTO THE PROGRAM AND AS

4180
02:29:49,464 --> 02:29:50,932
DAN WAS JUST MENTIONING, WE'VE

4181
02:29:50,932 --> 02:29:52,066
BEEN REALLY GEARING UP FOR THAT

4182
02:29:52,066 --> 02:29:53,301
AND I'LL HIGHLIGHT THAT IN THE

4183
02:29:53,301 --> 02:29:53,935
NEXT FEW SLIDES.

4184
02:29:53,935 --> 02:29:56,337
AND THEN WE WERE REALLY FOCUSING

4185
02:29:56,337 --> 02:29:57,705
AGAIN ON THE DIVERSITY OF OUR

4186
02:29:57,705 --> 02:29:58,573
ADVISORY BOARD.

4187
02:29:58,573 --> 02:30:01,276
AND WHAT'S UNIQUE IS I4C IS

4188
02:30:01,276 --> 02:30:01,943
INITY SECOND ITERATION SO WE

4189
02:30:01,943 --> 02:30:03,811
WERE ABLE TO ACTUALLY MAINTAIN

4190
02:30:03,811 --> 02:30:05,013
OUR COMMUNITY ADVISORY BOARD BUT

4191
02:30:05,013 --> 02:30:06,381
SINCE THEN WE'VE ALSO BEEN ABLE

4192
02:30:06,381 --> 02:30:07,615
TO GROW IT.

4193
02:30:07,615 --> 02:30:09,617
SO WE DO HAVE TWO NEW MEMBERS,

4194
02:30:09,617 --> 02:30:11,352
ONE OF WHICH IS IN THE ROOM, KIM

4195
02:30:11,352 --> 02:30:13,354
WILSON, AND THEN OUR OTHER

4196
02:30:13,354 --> 02:30:16,224
LONG-TERM MEMBER MARC WAGNER ARE

4197
02:30:16,224 --> 02:30:17,258
HERE REPRESENTING US.

4198
02:30:17,258 --> 02:30:18,026
ONE OF THE THINGS I WANT TO

4199
02:30:18,026 --> 02:30:19,427
HIGHLIGHT IS, SOMETHING THAT WE

4200
02:30:19,427 --> 02:30:20,528
REALLY VALUE AS FAR AS A METRIC

4201
02:30:20,528 --> 02:30:23,031
OF SUCCESS IS NOT JUST WHEN WE

4202
02:30:23,031 --> 02:30:24,332
ELEVATE AND CHAMPION OUR

4203
02:30:24,332 --> 02:30:26,100
PARTNERS, BUT WHEN THE FIELD

4204
02:30:26,100 --> 02:30:27,568
ELEVATES AND CHAMPIONS OUR

4205
02:30:27,568 --> 02:30:29,304
PARTNERS.

4206
02:30:29,304 --> 02:30:31,005
SO WE'RE REALLY EXCITED TO SEE

4207
02:30:31,005 --> 02:30:32,040
MARC WAGNER ON THE PANEL

4208
02:30:32,040 --> 02:30:34,642
YESTERDAY SPEAKING IN HIS OWN

4209
02:30:34,642 --> 02:30:35,510
EXPERTISE ON THE PRECISION

4210
02:30:35,510 --> 02:30:36,611
MEDICINE AND NEW GRANTS THAT ARE

4211
02:30:36,611 --> 02:30:37,145
COMING OUT.

4212
02:30:37,145 --> 02:30:38,613
SO THAT RECOGNITION BY THE FIELD

4213
02:30:38,613 --> 02:30:39,947
OF OUR PARTNERS AND THEIR

4214
02:30:39,947 --> 02:30:41,149
SUCCESS IS SOMETHING THAT WE

4215
02:30:41,149 --> 02:30:42,917
REALLY VALUE AS A METRIC THAT

4216
02:30:42,917 --> 02:30:44,519
WE'RE TRACKING OVER TIME.

4217
02:30:44,519 --> 02:30:45,920
WE HAVE BEEN ABLE TO BUILD THE

4218
02:30:45,920 --> 02:30:47,855
NUMBER OF LOCAL PARTNERSHIPS.

4219
02:30:47,855 --> 02:30:49,390
ONE IN PARTICULAR I WANTED TO

4220
02:30:49,390 --> 02:30:50,825
HIGHLIGHT WAS FENWAY HEALTH.

4221
02:30:50,825 --> 02:30:52,794
SO WE'VE REALLY BEEN WORKING

4222
02:30:52,794 --> 02:30:54,395
VERY STRATEGICALLY BUILDING THAT

4223
02:30:54,395 --> 02:30:55,496
BASE IN BOSTON, NOT JUST TO

4224
02:30:55,496 --> 02:30:57,465
THINK ABOUT HOW DO WE CONNECT

4225
02:30:57,465 --> 02:30:58,666
CURE IN THE LOCAL COMMUNITY, BUT

4226
02:30:58,666 --> 02:31:00,468
HOW DO WE BRIDGE IT IN THE

4227
02:31:00,468 --> 02:31:02,103
CONTEXT OF BOTH PREVENTION AND

4228
02:31:02,103 --> 02:31:04,806
TREATMENT, AND SO FENWAY HAS

4229
02:31:04,806 --> 02:31:07,008
BECOME A MAJOR PARTNER FOR US IN

4230
02:31:07,008 --> 02:31:08,009
THINKING ABOUT OUR EVENTS BUT

4231
02:31:08,009 --> 02:31:09,410
ALSO MOVING FORWARD HOW DO WE

4232
02:31:09,410 --> 02:31:10,712
BEGIN TO TRANSLATE THE MESSAGES

4233
02:31:10,712 --> 02:31:12,680
AND THE INFORMATION OF I4C OUT

4234
02:31:12,680 --> 02:31:13,781
INTO THE LARGER COMMUNITY.

4235
02:31:13,781 --> 02:31:18,686
AND THEN WE'VE ALSO -- WE DO

4236
02:31:18,686 --> 02:31:23,791
HAVE -- TANIA HENDERSON, OUR

4237
02:31:23,791 --> 02:31:25,426
CURE BOARD MEMBER WITH I4C IS

4238
02:31:25,426 --> 02:31:27,495
HERE AND SHE ACTUALLY DID SOME

4239
02:31:27,495 --> 02:31:29,664
LOCAL WORK IN BUILDING THIS OUT

4240
02:31:29,664 --> 02:31:32,734
IN A ANACOSTIA.

4241
02:31:32,734 --> 02:31:36,170
WE WERE ABLE TO HOLD A LOCAL

4242
02:31:36,170 --> 02:31:37,071
EVENT IN THE SOUTHEAST OF D.C. ,

4243
02:31:37,071 --> 02:31:38,606
IT'S REALLY AN UNDERSERVED

4244
02:31:38,606 --> 02:31:41,008
COMMUNITY, NOT JUST IN ITS

4245
02:31:41,008 --> 02:31:44,245
RESOURCES BUT -- JUST BUILT

4246
02:31:44,245 --> 02:31:45,046
THEIR FIRST CLINIC THERE IN

4247
02:31:45,046 --> 02:31:46,881
DECEMBER IT OPENED BUT THINKING

4248
02:31:46,881 --> 02:31:47,749
ABOUT ACKNOWLEDGMENT WHEN IT

4249
02:31:47,749 --> 02:31:49,684
COMES TO THIS INFORMATION.

4250
02:31:49,684 --> 02:31:51,352
SO WE'VE ALSO BEEN ABLE TO BUILD

4251
02:31:51,352 --> 02:31:52,019
LITERACY.

4252
02:31:52,019 --> 02:31:54,589
THERE'S A NUMBER OF REALLY

4253
02:31:54,589 --> 02:31:55,790
EXCITING TOOLS, JUST TO

4254
02:31:55,790 --> 02:31:57,225
HIGHLIGHT TWO IN PARTICULAR,

4255
02:31:57,225 --> 02:31:58,860
VICTORIA SPERLING WALKER IN

4256
02:31:58,860 --> 02:32:00,094
MARCH GAVE A FANTASTIC

4257
02:32:00,094 --> 02:32:01,562
PRESENTATION ON HOW TO

4258
02:32:01,562 --> 02:32:02,663
UNDERSTAND A SCIENTIFIC

4259
02:32:02,663 --> 02:32:03,765
PRESENTATION.

4260
02:32:03,765 --> 02:32:06,934
WHICH REALLY HAS OPENED UP A NEW

4261
02:32:06,934 --> 02:32:08,870
GATEWAY OF HOW DO WE THINK ABOUT

4262
02:32:08,870 --> 02:32:11,472
INNOVATIVE WAYS TO ENGAGE LAY

4263
02:32:11,472 --> 02:32:13,408
AUDIENCES IN THE SCIENCE.

4264
02:32:13,408 --> 02:32:14,709
AND AS SOMEBODY WHO IS NOT A

4265
02:32:14,709 --> 02:32:16,477
PH.D. OR AN M.D. MYSELF WHO

4266
02:32:16,477 --> 02:32:17,245
DOESN'T UNDERSTAND ALL THE

4267
02:32:17,245 --> 02:32:19,947
THINGS OF A HEAT MAP OR A

4268
02:32:19,947 --> 02:32:21,249
GENETIC DIVERSITY TREE, HAVING

4269
02:32:21,249 --> 02:32:22,583
SOMEBODY WALK THROUGH WHAT ARE

4270
02:32:22,583 --> 02:32:24,452
THE KEY AREAS ON THAT SLIDE THAT

4271
02:32:24,452 --> 02:32:27,355
I NEED TO UNDERSTAND IN ORDER TO

4272
02:32:27,355 --> 02:32:28,556
MEANINGFULLY ENGAGE IN THE

4273
02:32:28,556 --> 02:32:29,757
CONVERSATION HAS BEEN CRITICAL,

4274
02:32:29,757 --> 02:32:31,025
AND VICTORIA REALLY CREATED A

4275
02:32:31,025 --> 02:32:32,994
ROAD MAP THAT HAS BEEN ABLE TO

4276
02:32:32,994 --> 02:32:34,429
HELP US TAKE THOSE TOOLS AND

4277
02:32:34,429 --> 02:32:35,530
MOVE FORWARD.

4278
02:32:35,530 --> 02:32:38,666
WE ALSO HAVE A POCKET GUIDE.

4279
02:32:38,666 --> 02:32:40,635
AGAIN, YOU CAN FIND THESE, WE DO

4280
02:32:40,635 --> 02:32:43,938
HAVE AN INTERACTIVE PORTAL

4281
02:32:43,938 --> 02:32:45,606
CALLED ENGAGE.AVAC.ORG.

4282
02:32:45,606 --> 02:32:47,508
WE HAVE A SITE, IT'S COMPLETELY

4283
02:32:47,508 --> 02:32:48,709
FREE, A LEARNING MANAGEMENT

4284
02:32:48,709 --> 02:32:50,111
SYSTEM THAT HAS A NUMBER OF

4285
02:32:50,111 --> 02:32:50,978
TOOLS, PRESENTATIONS AND

4286
02:32:50,978 --> 02:32:52,647
RECORDED VIDEOS THAT CAN YOU

4287
02:32:52,647 --> 02:32:54,715
ACTUALLY TRACK AND DOWNLOAD AND

4288
02:32:54,715 --> 02:32:55,450
CREATE SOME OF THESE MATERIALS.

4289
02:32:55,450 --> 02:32:56,417
BUT THIS POCKET GUIDE IS MEANT

4290
02:32:56,417 --> 02:32:57,718
TO BE A PICTURE THAT CAN BE

4291
02:32:57,718 --> 02:33:00,321
PULLED UP ON A SMARTPHONE SO

4292
02:33:00,321 --> 02:33:01,556
THAT IF YOU'RE IN A PRESENTATION

4293
02:33:01,556 --> 02:33:02,990
OR A SESSION LIKE TODAY, YOU CAN

4294
02:33:02,990 --> 02:33:04,358
ACTUALLY JUST GO AHEAD AND

4295
02:33:04,358 --> 02:33:05,560
REFRESH YOURSELF ON WHAT THAT

4296
02:33:05,560 --> 02:33:06,761
SCIENCE MEANS.

4297
02:33:06,761 --> 02:33:08,729
SO WE'RE REALLY TRYING TO CREATE

4298
02:33:08,729 --> 02:33:09,630
BOTH INNOVATIVE TOOLS THAT CAN

4299
02:33:09,630 --> 02:33:13,367
BE USED IN A VARIETY OF SETTI 

4300
02:33:13,367 --> 02:33:13,868
SETTINGS.

4301
02:33:13,868 --> 02:33:14,902
I WANTED TO SAY AGAIN, WHEN WE

4302
02:33:14,902 --> 02:33:16,904
THINK ABOUT THE INFLUENCE, IT'S

4303
02:33:16,904 --> 02:33:17,772
REALLY IMPORTANT THAT WE'RE NOT

4304
02:33:17,772 --> 02:33:19,273
JUST THINKING ABOUT LITERACY.

4305
02:33:19,273 --> 02:33:21,042
LITERACY IS ONE COMPONENT OF

4306
02:33:21,042 --> 02:33:22,677
COMMUNITY ENGAGEMENT, BUT THE

4307
02:33:22,677 --> 02:33:26,247
TREUP METRUE METRIC OF SUCCESS W

4308
02:33:26,247 --> 02:33:27,215
ARE WE PUSHING THAT ENVIRONMENT

4309
02:33:27,215 --> 02:33:28,416
TO GO EVEN FURTHER?

4310
02:33:28,416 --> 02:33:30,585
AND SO FOR US, CREATING THAT

4311
02:33:30,585 --> 02:33:31,786
ENABLING ENVIRONMENT HAS BEEN

4312
02:33:31,786 --> 02:33:32,220
KEY.

4313
02:33:32,220 --> 02:33:34,188
AND SO SOME OF THE WAYS IS WE'RE

4314
02:33:34,188 --> 02:33:35,923
THINKING AGAIN ABOUT THE

4315
02:33:35,923 --> 02:33:38,526
INTEGRATION WITH POLICY MAKERS,

4316
02:33:38,526 --> 02:33:40,728
AND SANDY JOINED US ON A PANEL

4317
02:33:40,728 --> 02:33:43,097
NEAR HIV VACCINE AWARENESS DAY

4318
02:33:43,097 --> 02:33:45,399
TO BRIDGE CURE INTO THE

4319
02:33:45,399 --> 02:33:46,667
CONVERSATIONS AROUND PREVENTION

4320
02:33:46,667 --> 02:33:48,336
AND TREATMENT WITH OUR

4321
02:33:48,336 --> 02:33:49,504
LAWMAKERS, AND SO THAT'S REALLY

4322
02:33:49,504 --> 02:33:50,271
IMPORTANT TO AGAIN THINKING

4323
02:33:50,271 --> 02:33:51,606
ABOUT HOW DO WE SUSTAIN FUNDING

4324
02:33:51,606 --> 02:33:53,140
AND HOW DO WE PUT A SPOTLIGHT ON

4325
02:33:53,140 --> 02:33:55,409
THE WORK THAT WE'RE DOING.

4326
02:33:55,409 --> 02:33:57,144
WE'VE ALSO DONE A LOT OF WORK

4327
02:33:57,144 --> 02:33:59,080
INTERVENING WITH CLINICIANS,

4328
02:33:59,080 --> 02:34:01,516
PEOPLE LIVING WITH HIV POST

4329
02:34:01,516 --> 02:34:02,917
INTERVENTION CONTROLLERS,

4330
02:34:02,917 --> 02:34:03,918
SPONSORS AND OTHERS TO NOT JUST

4331
02:34:03,918 --> 02:34:05,887
THINK ABOUT ERADICATION, BUT

4332
02:34:05,887 --> 02:34:07,622
WHAT DOES CONTROL MEAN AND WHAT

4333
02:34:07,622 --> 02:34:09,090
ARE THOSE CONSIDERATIONS.

4334
02:34:09,090 --> 02:34:10,191
AND THIS WORK WAS ACTUALLY LED

4335
02:34:10,191 --> 02:34:16,163
BY, AGAIN, ONE OF OUR CURE

4336
02:34:16,163 --> 02:34:17,031
MEMBERS, WHOSE PICTURE IS UP

4337
02:34:17,031 --> 02:34:17,698
THERE.

4338
02:34:17,698 --> 02:34:19,200
AND WE'VE JUST FOUND THAT THIS

4339
02:34:19,200 --> 02:34:20,868
HAS BEEN A FANTASTIC PROJECT,

4340
02:34:20,868 --> 02:34:23,271
AGAIN TO THINK ABOUT INFLUENCING

4341
02:34:23,271 --> 02:34:24,805
THE CONVERSATION AND THE

4342
02:34:24,805 --> 02:34:27,308
NARRATIVE MOVING FORWARD.

4343
02:34:27,308 --> 02:34:29,076
LAST THING I WANTED TO SAY IS,

4344
02:34:29,076 --> 02:34:31,979
YOU KNOW, WE'RE FOCUSED ON THE

4345
02:34:31,979 --> 02:34:34,382
SCIENCE, AND I FORESEE HAS

4346
02:34:34,382 --> 02:34:36,017
REALLY THOUGHT A LOT ABOUT THE

4347
02:34:36,017 --> 02:34:36,651
BENCH BUT WE'RE ALSO THINKING

4348
02:34:36,651 --> 02:34:40,154
WIABOUT HOW DO WE TRANSLATE THA,

4349
02:34:40,154 --> 02:34:41,556
HOW DO WE BRING THAT OUT NOW.

4350
02:34:41,556 --> 02:34:44,091
YOU HEARD A LOT O ABOUT THE

4351
02:34:44,091 --> 02:34:45,760
VARIOUS COHORTS AND THE WORK

4352
02:34:45,760 --> 02:34:46,460
BEING DONE IN MHRP AND THINKING

4353
02:34:46,460 --> 02:34:49,063
ABOUT THOSE BIO SAMPLES.

4354
02:34:49,063 --> 02:34:50,431
WE'RE THINKING ABOUT HOW DO WE

4355
02:34:50,431 --> 02:34:51,465
PLAN FROM THE TRANSITION FROM

4356
02:34:51,465 --> 02:34:52,800
THE BENCH REALLY INTO THOSE

4357
02:34:52,800 --> 02:34:54,201
LARGER SCALE CLINICAL TRIALS AS

4358
02:34:54,201 --> 02:34:54,969
THEY MOVE FORWARD.

4359
02:34:54,969 --> 02:34:56,037
SO WE'RE REALLY EXCITED THAT

4360
02:34:56,037 --> 02:34:58,873
WE'VE NOT ONLY HAD OUR CAB

4361
02:34:58,873 --> 02:35:03,110
MEMBERS BE AT THE ADVOCACY FOR A

4362
02:35:03,110 --> 02:35:04,312
CURE ACADEMY, BUT WE'VE ALSO

4363
02:35:04,312 --> 02:35:06,547
BEEN ABLE TO CREATE AN ENABLING

4364
02:35:06,547 --> 02:35:07,882
ENVIRONMENT IN OTHER WAYS.

4365
02:35:07,882 --> 02:35:09,317
WE'VE ACTUALLY CREATED A

4366
02:35:09,317 --> 02:35:10,985
JOURNALIST TRAINING THAT FOCUSES

4367
02:35:10,985 --> 02:35:12,987
ON COMMUNICATION THAT WAS A

4368
02:35:12,987 --> 02:35:13,788
YEAR-LONG ENDEAVOR WHERE

4369
02:35:13,788 --> 02:35:16,724
JOURNALISTS MET MONTHLY IN

4370
02:35:16,724 --> 02:35:18,392
ZIMBABWE, WHICH WAS

4371
02:35:18,392 --> 02:35:21,395
STRATEGICALLY CHOSEN FORTY

4372
02:35:21,395 --> 02:35:23,030
CONNECTION TO TWO UPCOMING FIRST

4373
02:35:23,030 --> 02:35:24,899
IN COUNTRY ATI TRIALS THAT ARE

4374
02:35:24,899 --> 02:35:25,333
HAPPENING THERE.

4375
02:35:25,333 --> 02:35:26,734
AND THROUGH THAT YEAR, WE MET

4376
02:35:26,734 --> 02:35:29,270
WITH JOURNALISTS, TRAINED THEM

4377
02:35:29,270 --> 02:35:30,404
ABOUT THE SCIENCE, HOW TO

4378
02:35:30,404 --> 02:35:31,572
COMMUNICATE IT, AND WHAT WERE

4379
02:35:31,572 --> 02:35:33,741
THE KEY MESSAGES, AND YOU CAN

4380
02:35:33,741 --> 02:35:34,809
SEE HERE A SMATTERING OF THE

4381
02:35:34,809 --> 02:35:36,644
PAPERS THAT THEY ALL WROTE,

4382
02:35:36,644 --> 02:35:38,412
STORIES THAT CAME OUT OF THAT

4383
02:35:38,412 --> 02:35:38,946
12-MONTH PROGRAM.

4384
02:35:38,946 --> 02:35:40,381
THAT PROGRAM IS NOW GOING TO BE

4385
02:35:40,381 --> 02:35:43,084
PILOTED OUT INTO OTHER COUNTRIES

4386
02:35:43,084 --> 02:35:43,951
CONDUCTING ATI CLINICAL TRIALS

4387
02:35:43,951 --> 02:35:47,221
AS WELL, SO THINK THINK ABOUT U,

4388
02:35:47,221 --> 02:35:51,359
SOUTH AFRICA AND KENYA, AND

4389
02:35:51,359 --> 02:35:53,227
AGAIN THE MATERIALS THAT WERE

4390
02:35:53,227 --> 02:35:56,397
CREATED BY THIS FELLOW, ANNA

4391
02:35:56,397 --> 02:35:58,232
MITI, REALLY HELPS TO BRING IN

4392
02:35:58,232 --> 02:35:59,667
AND DIVERSIFY, SHE ACTUALLY

4393
02:35:59,667 --> 02:36:01,736
TRANSLATED INTO TWO LOCAL

4394
02:36:01,736 --> 02:36:02,770
DIALECTS THAT ARE BEING USED NOW

4395
02:36:02,770 --> 02:36:06,874
IN THE ACTG5417 TRIAL SITE IN

4396
02:36:06,874 --> 02:36:07,575
SIB BAB WAY.

4397
02:36:07,575 --> 02:36:14,749
ZIMBABWE.

4398
02:36:14,749 --> 02:36:20,755
MANDISA DUKASHE -- AND BROUGHT

4399
02:36:20,755 --> 02:36:22,056
PARTNERS TO REALLY HELP MOVE

4400
02:36:22,056 --> 02:36:23,357
THAT WORK FORWARD.

4401
02:36:23,357 --> 02:36:25,092
THEN UDOM, OUR CAB MEMBER BASED

4402
02:36:25,092 --> 02:36:26,527
IN THAILAND HAS BEEN WORKING

4403
02:36:26,527 --> 02:36:29,463
WITH MHRP TO REALLY CREATE SOME

4404
02:36:29,463 --> 02:36:30,698
CURE-FOCUSED CABs, THINKING

4405
02:36:30,698 --> 02:36:31,532
ABOUT SOME OF THESE NEW

4406
02:36:31,532 --> 02:36:32,400
PROTOCOLS AND STUDIES THAT ARE

4407
02:36:32,400 --> 02:36:33,167
GOING OUT THERE.

4408
02:36:33,167 --> 02:36:36,337
SO REALLY EXCITE FOD ED TO SEE S

4409
02:36:36,337 --> 02:36:37,605
WORK MOVE FORWARD INTO THE NEXT

4410
02:36:37,605 --> 02:36:37,805
PHASE.

4411
02:36:37,805 --> 02:36:39,040
SO WITH THAT, I'M HAPPY TO TAKE

4412
02:36:39,040 --> 02:36:41,242
ANY QUESTIONS, AND REALLY LOOK

4413
02:36:41,242 --> 02:36:42,043
FORWARD TO THE WORK.

4414
02:36:42,043 --> 02:36:49,650
[APPLAUSE]

4415
02:36:49,650 --> 02:36:50,518
>> SO THANK YOU VERY MUCH.

4416
02:36:50,518 --> 02:36:51,719
WE ARE PERFECTLY ON TIME.

4417
02:36:51,719 --> 02:36:52,687
WE HAVE TIME FOR A FEW

4418
02:36:52,687 --> 02:36:53,988
QUESTIONS.

4419
02:36:53,988 --> 02:36:59,026
PLEASE COME TO THE MICROPHONE.

4420
02:36:59,026 --> 02:36:59,660
>> HI.

4421
02:36:59,660 --> 02:37:01,629
MY QUESTION IS FOR DR. VASAN.

4422
02:37:01,629 --> 02:37:02,897
EVERYBODY, THIS IS A GREAT TALK,

4423
02:37:02,897 --> 02:37:03,798
THANK YOU.

4424
02:37:03,798 --> 02:37:09,470
SO I THINK -- YOUR 50% OF THE

4425
02:37:09,470 --> 02:37:11,205
PARTICIPANTS WHO FAILED IPDA,

4426
02:37:11,205 --> 02:37:13,441
THEY WERE DEFECTS IN -- SHOULD I

4427
02:37:13,441 --> 02:37:15,042
KNOW THIS, JOHN?

4428
02:37:15,042 --> 02:37:18,446
>> SO MOST CLONES THAT WE
KNOW

4429
02:37:18,446 --> 02:37:21,215
ARE DEFECTIVE --

4430
02:37:21,215 --> 02:37:23,651
>> IN -- OR PSI OR DO YOU
KNOW?

4431
02:37:23,651 --> 02:37:26,387
>> IT LOOKS LIKE PSI.

4432
02:37:26,387 --> 02:37:28,122
>> OKAY.

4433
02:37:28,122 --> 02:37:30,758
SO DO YOU HAVE ANY -- ARE YOU

4434
02:37:30,758 --> 02:37:32,093
PLANNING TO DO PROVIRAL

4435
02:37:32,093 --> 02:37:33,794
SEQUENCING OR PSI SEQUENCING

4436
02:37:33,794 --> 02:37:35,896
BECAUSE YOU COULD -- IN TITAN

4437
02:37:35,896 --> 02:37:37,965
AND ECLEAR WE DESIGNED PRIMERS

4438
02:37:37,965 --> 02:37:39,500
AND PROBES SPECIFIC TO

4439
02:37:39,500 --> 02:37:41,001
PARTICIPANTS, EACH PARTICIPANT,

4440
02:37:41,001 --> 02:37:42,236
IT'S A HEADACHE BUT IT CAN BE

4441
02:37:42,236 --> 02:37:43,537
DONE IF YOU'RE GOING TO FOLLOW

4442
02:37:43,537 --> 02:37:44,071
THEM LONG TERM.

4443
02:37:44,071 --> 02:37:46,907
>> GOOD QUESTION.

4444
02:37:46,907 --> 02:37:48,776
SO LEIA BRANT IS IN THE

4445
02:37:48,776 --> 02:37:49,076
AUDIENCE.

4446
02:37:49,076 --> 02:37:51,445
WE ARE TAKING INDIVIDUAL PRO

4447
02:37:51,445 --> 02:37:54,415
VIRUSES, SEQUENCING THEM, AND

4448
02:37:54,415 --> 02:37:57,818
SEEING WHETHER THE SEQUENCE HAS

4449
02:37:57,818 --> 02:38:00,788
A RRE OR PSI BINDING REGION.

4450
02:38:00,788 --> 02:38:02,723
AND IF IT DOES, WHETHER IT'S

4451
02:38:02,723 --> 02:38:04,258
LIKELY TO READ OUT POSITIVE IN

4452
02:38:04,258 --> 02:38:07,528
THE IPDA BASED ON THE MATCH.

4453
02:38:07,528 --> 02:38:10,364
WHAT WE'RE FINDING IS THE VAST

4454
02:38:10,364 --> 02:38:13,768
MAJORITY OF CLONES, OF PRO

4455
02:38:13,768 --> 02:38:16,704
VIRUSES ARE DEFECTIVE.

4456
02:38:16,704 --> 02:38:18,239
THE ONES THAT WE'VE IDENTIFIED

4457
02:38:18,239 --> 02:38:23,410
SO FAR THAT ARE CLONAL AND NEAR

4458
02:38:23,410 --> 02:38:28,549
FULL LENGTH, A FEW ARE INTACT,

4459
02:38:28,549 --> 02:38:29,917
ABOUT 50% THAT WOULD BE DETECTED

4460
02:38:29,917 --> 02:38:35,589
BY THE IPDA, AND THE OTHER HALF

4461
02:38:35,589 --> 02:38:37,124
HAVE EITHER DELETION IN PSI

4462
02:38:37,124 --> 02:38:38,826
MOSTLY OR RRE.

4463
02:38:38,826 --> 02:38:40,494
>> OKAY, THANKS.

4464
02:38:40,494 --> 02:38:41,595
>> CHRIS PETERSON.

4465
02:38:41,595 --> 02:38:43,864
>> ALSO FOR JOHN.

4466
02:38:43,864 --> 02:38:46,133
WE'VE ALSO SEEN APT-CAR

4467
02:38:46,133 --> 02:38:48,435
ANTIBODIES OUTSIDE OF THAT HUMAN

4468
02:38:48,435 --> 02:38:50,437
CD4 DOMAIN, AND WE CAN SHOW IN

4469
02:38:50,437 --> 02:38:51,505
VITRO THAT THEY DO RESTRICT

4470
02:38:51,505 --> 02:38:54,341
FUNCTION, BUT IT'S NEVER LINED

4471
02:38:54,341 --> 02:38:56,177
UP IN VIVO, THAT WE'RE LOSING

4472
02:38:56,177 --> 02:38:57,711
CARS WAY BEFORE WE SEE THOSE

4473
02:38:57,711 --> 02:38:58,145
ANTIBODIES.

4474
02:38:58,145 --> 02:39:01,182
SO I'M WONDERING IF YOU HAVE ANY

4475
02:39:01,182 --> 02:39:01,949
CAUSATIVE EVIDENCE THAT THE

4476
02:39:01,949 --> 02:39:02,817
ANTIBODIES OR WHAT IS

4477
02:39:02,817 --> 02:39:05,786
RESTRICTING THE CAR FUNCTION IN

4478
02:39:05,786 --> 02:39:09,690
VIVO.

4479
02:39:09,690 --> 02:39:12,059
>> SO THE ANALYSES WERE
JUST

4480
02:39:12,059 --> 02:39:13,794
INITIAL LOOK, AND DAN DID THOSE

4481
02:39:13,794 --> 02:39:15,563
ANALYSES.

4482
02:39:15,563 --> 02:39:17,598
SO CARs DISAPPEAR, ANTIBODY

4483
02:39:17,598 --> 02:39:17,832
APPEAR.

4484
02:39:17,832 --> 02:39:19,033
IS THAT CAUSAL?

4485
02:39:19,033 --> 02:39:21,669
WE DON'T -- WE DON'T KNOW THAT

4486
02:39:21,669 --> 02:39:22,636
FOR SURE.

4487
02:39:22,636 --> 02:39:23,938
IT'S CORRELATIVE.

4488
02:39:23,938 --> 02:39:26,774
THERE MAY BE OTHER MECHANISMS

4489
02:39:26,774 --> 02:39:29,210
WHEREBY CARs DON'T PERSIST.

4490
02:39:29,210 --> 02:39:33,247
AND JIM, PLEASE FEEL FREE TO GET

4491
02:39:33,247 --> 02:39:34,415
UP AND -- HE'S HAPPY WITH WHAT I

4492
02:39:34,415 --> 02:39:36,083
SAID.

4493
02:39:36,083 --> 02:39:36,350
[LAUGHTER]

4494
02:39:36,350 --> 02:39:40,955
>> I CAN ANSWER A
FOLLOW-UP TO

4495
02:39:40,955 --> 02:39:41,856
THAT QUESTION ALSO.

4496
02:39:41,856 --> 02:39:45,359
WHEN WE INFUSE THE CAR-T CELLS

4497
02:39:45,359 --> 02:39:46,660
INITIALLY, THEN THE TWO

4498
02:39:46,660 --> 02:39:49,864
OBSERVATIONS ARE THAT THE CAR-T

4499
02:39:49,864 --> 02:39:51,899
CELLS DISAPPEARED CONCURRENTLY

4500
02:39:51,899 --> 02:39:54,401
WITH THE ANTICD4 ANTIBODIES

4501
02:39:54,401 --> 02:39:57,972
APPEARING, AND THEN WE ACTUALLY

4502
02:39:57,972 --> 02:39:58,973
DID ANOTHER PHASE OF THE STUDY

4503
02:39:58,973 --> 02:40:01,542
WHERE WE DID A SECOND INFUSION

4504
02:40:01,542 --> 02:40:03,711
OF CAR-T CELLS IN THE SAME

4505
02:40:03,711 --> 02:40:05,145
ANIMALS, AND IN THE SETTING OF

4506
02:40:05,145 --> 02:40:06,347
THE PRESENCE OF THOSE

4507
02:40:06,347 --> 02:40:09,817
ANTIBODIES, THERE WAS NO --

4508
02:40:09,817 --> 02:40:12,519
THERE WAS NOT EVEN AN EARLY

4509
02:40:12,519 --> 02:40:13,687
ACUTE TAKE, SO IT WAS A COMPLETE

4510
02:40:13,687 --> 02:40:15,089
BLOCKADE OF ANY CAR-T CELLS IN

4511
02:40:15,089 --> 02:40:16,457
THE PRESENCE OF THE ANTIBODIES.

4512
02:40:16,457 --> 02:40:19,226
>> PREINFUSION I TOTALLY
AGREE,

4513
02:40:19,226 --> 02:40:20,728
BUT THE FIRST ONE, THAT'S WHAT

4514
02:40:20,728 --> 02:40:21,629
I'M CURIOUS ABOUT.

4515
02:40:21,629 --> 02:40:23,230
>> SO I THINK IT'S QUITE

4516
02:40:23,230 --> 02:40:25,633
CONVINCING EVIDENCE THAT THE

4517
02:40:25,633 --> 02:40:27,835
ANTIHUMAN CD4 ANTIBODIES WERE

4518
02:40:27,835 --> 02:40:30,771
INDUCED BY THE CAR-T CELLS AND

4519
02:40:30,771 --> 02:40:32,673
PREVENTED THE SECOND

4520
02:40:32,673 --> 02:40:38,879
ADMINISTRATION OF THEM.

4521
02:40:38,879 --> 02:40:40,314
>> THANK YOU FOR TALKING
ABOUT

4522
02:40:40,314 --> 02:40:41,949
THE GLOBAL ENGAGEMENT PORTFOLIO

4523
02:40:41,949 --> 02:40:42,683
AND THE WONDERFUL WORK THAT

4524
02:40:42,683 --> 02:40:47,621
YOU'RE DOING IN AFRICA.

4525
02:40:47,621 --> 02:40:48,789
CAN YOU TALK A LITTLE ABOUT THE

4526
02:40:48,789 --> 02:40:49,924
PROCESS FOR INCORPORATING

4527
02:40:49,924 --> 02:40:50,791
COMMUNITY RECOMMENDATIONS INTO

4528
02:40:50,791 --> 02:40:52,860
CLINICAL TRIAL DESIGNS,

4529
02:40:52,860 --> 02:40:55,129
PARTICULARLY THOSE INVOLVING

4530
02:40:55,129 --> 02:40:56,897
ATIs, AND WHAT HAS THAT UPTAKE

4531
02:40:56,897 --> 02:40:59,767
BEEN LIKE?

4532
02:40:59,767 --> 02:41:01,168
>> THANKS, KARINE, FOR THE

4533
02:41:01,168 --> 02:41:01,435
QUESTION.

4534
02:41:01,435 --> 02:41:03,103
YOU KNOW, WHEN WE THINK ABOUT

4535
02:41:03,103 --> 02:41:03,904
THE GLOBAL PRESENCE, THIS

4536
02:41:03,904 --> 02:41:04,638
MEETING WAS IN JUNE.

4537
02:41:04,638 --> 02:41:06,206
SINCE THEN, THE STAKEHOLDERS

4538
02:41:06,206 --> 02:41:09,576
HAVE CONTINUED TO MEET, THIS

4539
02:41:09,576 --> 02:41:10,778
SMALL GROUP OF ADVOCATES HAVE

4540
02:41:10,778 --> 02:41:12,079
CONTINUED TO MEET MONTHLY TO

4541
02:41:12,079 --> 02:41:13,480
KIND OF TALK ABOUT THAT AND ARE

4542
02:41:13,480 --> 02:41:15,015
WORKING WITH THE CLINICAL TRIAL

4543
02:41:15,015 --> 02:41:17,217
PIs TO SEE HOW WE CAN

4544
02:41:17,217 --> 02:41:18,218
INCORPORATE THEIR THOUGHTS AND

4545
02:41:18,218 --> 02:41:20,254
FEEDBACK.

4546
02:41:20,254 --> 02:41:21,689
BECAUSE IT WAS DONE AFTER THE

4547
02:41:21,689 --> 02:41:23,424
PROTOCOL WAS SEALED, WE ARE

4548
02:41:23,424 --> 02:41:25,926
REALLY THINKING ABOUT HOW DO WE

4549
02:41:25,926 --> 02:41:28,262
PUSH FOR EITHER A STATEMENT

4550
02:41:28,262 --> 02:41:29,763
POSITION OR SOMETHING ELSE THAT,

4551
02:41:29,763 --> 02:41:31,098
AGAIN, IS LED BY THE ADVOCATES

4552
02:41:31,098 --> 02:41:33,167
THAT WERE IN THE ROOM ON WHAT

4553
02:41:33,167 --> 02:41:34,268
THEY WANT TO DO, BUT WHAT WE'VE

4554
02:41:34,268 --> 02:41:38,973
BEEN ABLE TO DO TO PUSH THEIR

4555
02:41:38,973 --> 02:41:41,208
FEELINGS IS THEY'VE HELD A LOT

4556
02:41:41,208 --> 02:41:43,444
OF SESSIONS IN CONJUNCTION WITH

4557
02:41:43,444 --> 02:41:45,279
U EQUAL U FORUMS TO TALK ABOUT

4558
02:41:45,279 --> 02:41:47,681
ATIs TO DELIVER THAT FEEDBACK,

4559
02:41:47,681 --> 02:41:49,016
AND WE'RE BEGINNING TO AGAIN

4560
02:41:49,016 --> 02:41:50,584
FEED THAT BACK INTO THE CLINICAL

4561
02:41:50,584 --> 02:41:52,619
TRIALS PROCESS WITH THE ACTG.

4562
02:41:52,619 --> 02:41:54,355
>> I'D LIKE TO ADD TO THAT

4563
02:41:54,355 --> 02:41:56,223
BRIEFLY BY JUST STATING THAT WE

4564
02:41:56,223 --> 02:41:58,492
AT LEAST FOR SOME OF OUR TRIALS

4565
02:41:58,492 --> 02:42:00,894
IN THAILAND, WE'VE BEEN WORKING

4566
02:42:00,894 --> 02:42:04,531
WITH GAIL HENDERSON AND HOLLY

4567
02:42:04,531 --> 02:42:08,569
PIA THROUGH AN R01 THAT WAS

4568
02:42:08,569 --> 02:42:09,970
FUNDED, ACTUALLY SOMEWHAT

4569
02:42:09,970 --> 02:42:11,972
QUANTITATIVE, ABOUT ANALYZING

4570
02:42:11,972 --> 02:42:13,807
PARTICIPANTS' ATTITUDES, FEAR,

4571
02:42:13,807 --> 02:42:16,343
CONCERNS AND WILLINGNESS TO

4572
02:42:16,343 --> 02:42:18,512
PARTICIPATE IN ATI STUDIES,

4573
02:42:18,512 --> 02:42:19,713
PARTNER PROTECTION AND ALSO

4574
02:42:19,713 --> 02:42:22,049
SHORT VERSUS LONG DURATION

4575
02:42:22,049 --> 02:42:22,249
ATIs.

4576
02:42:22,249 --> 02:42:24,318
A LOT OF THAT WORK IS NOW

4577
02:42:24,318 --> 02:42:26,186
PUBLISHED, AND HAS REALLY BEEN

4578
02:42:26,186 --> 02:42:27,788
INSTRUMENTAL IN GUIDING US IN

4579
02:42:27,788 --> 02:42:30,224
ADVANCE FOR THE DESIGN OF OUR

4580
02:42:30,224 --> 02:42:31,859
NEXT UPCOMING TRIAL THAT'S

4581
02:42:31,859 --> 02:42:34,528
OUTSIDE OF THE I4C BUT WE ARE

4582
02:42:34,528 --> 02:42:37,431
LEVERAGING THE I4C MECHANISM TO

4583
02:42:37,431 --> 02:42:39,500
ENGAGE THE CABs AND

4584
02:42:39,500 --> 02:42:43,771
SPECIFICALLY IN THIS CASE OUR --

4585
02:42:43,771 --> 02:42:44,738
CAB MEMBER.

4586
02:42:44,738 --> 02:42:45,773
AS WE TALKED ABOUT IN OUR

4587
02:42:45,773 --> 02:42:46,507
COMMUNITY MEETING YESTERDAY,

4588
02:42:46,507 --> 02:42:47,608
THERE ARE ASPECTS OF COMMUNITY

4589
02:42:47,608 --> 02:42:49,076
FEEDBACK THAT I THINK ARE

4590
02:42:49,076 --> 02:42:50,778
UNIVERSAL, AND THEN OTHERS THAT

4591
02:42:50,778 --> 02:42:52,079
ARE CULTURE-SPECIFIC AND WE NEED

4592
02:42:52,079 --> 02:42:54,748
TO BE SENSITIVE TO BOTH.

4593
02:42:54,748 --> 02:42:57,351
>> CAN YOU STATE YOUR NAME
AND

4594
02:42:57,351 --> 02:42:57,785
AFFILIATION, PLEASE?

4595
02:42:57,785 --> 02:42:58,085
THANK YOU.

4596
02:42:58,085 --> 02:43:01,488
>> THANK YOU SO MUCH.

4597
02:43:01,488 --> 02:43:03,390
JOSEPHINE FROM UGANDA, REPRESENT

4598
02:43:03,390 --> 02:43:04,758
PEOPLE LIVING WITH HIV.

4599
02:43:04,758 --> 02:43:07,628
AND MY QUESTION IS ABOUT THE --

4600
02:43:07,628 --> 02:43:08,829
MOST TIMES WHEN YOU TALK ABOUT

4601
02:43:08,829 --> 02:43:10,264
THEM IN OUR COMMUNITY, WE STILL

4602
02:43:10,264 --> 02:43:12,433
MAKE A STATEMENT OF ATTITUDEMENT

4603
02:43:12,433 --> 02:43:15,035
HAS AN EFFECT ON THE SIZE OF THE

4604
02:43:15,035 --> 02:43:17,137
RESERVOIR, BUT MOST TIMES PEOPLE

4605
02:43:17,137 --> 02:43:21,008
ASK WHAT IS A ILI, IS THERE A

4606
02:43:21,008 --> 02:43:22,042
DEFINITION OF WHAT -- MEANS.

4607
02:43:22,042 --> 02:43:24,244
IS IT LIKE HOURS AFTER YOU'VE

4608
02:43:24,244 --> 02:43:26,413
BEEN INFECTED WITH HIV, IS IT

4609
02:43:26,413 --> 02:43:27,848
LIKE JUST YEARS AFTER YOU'VE

4610
02:43:27,848 --> 02:43:31,251
BEEN INFECTED WITH HIV?

4611
02:43:31,251 --> 02:43:35,389
THANK YOU.

4612
02:43:35,389 --> 02:43:36,190
>> THANKS FOR THAT
QUESTION.

4613
02:43:36,190 --> 02:43:39,026
THERE'S A SYSTEM CALLED FEIBIG

4614
02:43:39,026 --> 02:43:40,227
STAGES THAT'S BASED ON THE

4615
02:43:40,227 --> 02:43:42,296
TIMING OF APPEARANCE OF

4616
02:43:42,296 --> 02:43:44,298
DIFFERENT LABORATORIES

4617
02:43:44,298 --> 02:43:45,499
ANTIBODIES, WESTERN BLOT, VIRAL

4618
02:43:45,499 --> 02:43:47,267
LOAD, AND SO REALLY WE'RE

4619
02:43:47,267 --> 02:43:48,869
TALKING ABOUT A PERIOD OF WEEKS

4620
02:43:48,869 --> 02:43:51,939
TO MONTHS IN TERMS OF ACUTE TO

4621
02:43:51,939 --> 02:43:52,806
EARLY.

4622
02:43:52,806 --> 02:43:55,309
AND THAT'S WHY WE ALSO KNOW THAT

4623
02:43:55,309 --> 02:43:57,611
THAT'S VERY DIFFICULT TO ACHIEVE

4624
02:43:57,611 --> 02:44:00,047
FOR MOST OF THE WORLD.

4625
02:44:00,047 --> 02:44:01,315
IRRESPECTIVE OF WHAT COUNTRY YOU

4626
02:44:01,315 --> 02:44:01,548
LIVE IN.

4627
02:44:01,548 --> 02:44:03,951
SO THAT'S WHY STUDIES LIKE THE

4628
02:44:03,951 --> 02:44:07,554
ONE CONDUCTED BY DR. BAROUCH

4629
02:44:07,554 --> 02:44:09,990
HERE MODELING THE IMPACT OF THE

4630
02:44:09,990 --> 02:44:13,160
RESERVOIR ON PEOPLE WHO HAVE NOT

4631
02:44:13,160 --> 02:44:14,261
STARTED ART FOR YEARS AFTER

4632
02:44:14,261 --> 02:44:15,762
BEING EXPOSED TO HIV ARE EQUALLY

4633
02:44:15,762 --> 02:44:19,366
IMPORTANT.

4634
02:44:19,366 --> 02:44:27,474
>> DEBBIE

4635
02:44:27,474 --> 02:44:30,177
>> INTUITIVELY YOU WOULD
THINK

4636
02:44:30,177 --> 02:44:33,247
IT'S BASED ON INFECTED CELL

4637
02:44:33,247 --> 02:44:37,618
FREQUENCY, THINK VIREMIA.

4638
02:44:37,618 --> 02:44:42,756
I WONDER GIVEN DATE  DATA PRESED

4639
02:44:42,756 --> 02:44:43,857
YESTERDAY, HAVE YOU BEEN ABLE TO

4640
02:44:43,857 --> 02:44:46,760
LOOK AT AUTOLOGOUS

4641
02:44:46,760 --> 02:44:47,461
NEUTRALIZATION ANTIBODY AND TIME

4642
02:44:47,461 --> 02:44:50,297
IN RESET TO VIRAL ROAD TO KIND

4643
02:44:50,297 --> 02:44:52,633
OF TEASE OUT ARE THERE ANY

4644
02:44:52,633 --> 02:44:53,700
IMMUNE POTENTIAL MECHANISMS THAT

4645
02:44:53,700 --> 02:44:56,303
WE NEED TO CONSIDER WITH HIGH

4646
02:44:56,303 --> 02:44:58,605
LOAD VIREMIA, OR EVEN

4647
02:44:58,605 --> 02:45:00,474
SPECIFICALLY THE TIMING OF WHEN

4648
02:45:00,474 --> 02:45:03,443
TO STOP ATI IN TERMS OF A CELL

4649
02:45:03,443 --> 02:45:05,846
INFECTED -- INFECTED CELL

4650
02:45:05,846 --> 02:45:06,146
FREQUENCY?

4651
02:45:06,146 --> 02:45:07,347
>> THAT'S SPOT-ON.

4652
02:45:07,347 --> 02:45:08,382
WE'RE LOOKING AT THAT NOW.

4653
02:45:08,382 --> 02:45:09,917
WE DON'T HAVE THOSE DATA.

4654
02:45:09,917 --> 02:45:11,418
WE'RE ALSO COGNIZANT THAT WE'RE

4655
02:45:11,418 --> 02:45:12,753
LOOKING IN A SUBTYPE AE

4656
02:45:12,753 --> 02:45:14,388
POPULATION WHERE THE VIRUS IS

4657
02:45:14,388 --> 02:45:15,489
RELATIVELY MORE HO KNOWLEDGE

4658
02:45:15,489 --> 02:45:18,559
NUSS, SO I THINK THAT WARRANTS

4659
02:45:18,559 --> 02:45:19,893
REPLICATION ACROSS COHORTS.

4660
02:45:19,893 --> 02:45:23,897
>> JUST TO ADD TO THAT,
THERE'S

4661
02:45:23,897 --> 02:45:28,302
OLD DATA THAT THE SINGLE BEST

4662
02:45:28,302 --> 02:45:29,269
PREDICTOR OF THE LEVEL -- THE

4663
02:45:29,269 --> 02:45:30,704
FREQUENCY AND LEVEL OF

4664
02:45:30,704 --> 02:45:34,274
PERSISTENT VIREMIA ON ART IS THE

4665
02:45:34,274 --> 02:45:35,509
PRE-ART VIRAL LOAD.

4666
02:45:35,509 --> 02:45:38,579
SO IT'S CONSISTENT THAT THE

4667
02:45:38,579 --> 02:45:40,547
NUMBER OF INFECTED CELLS AT THE

4668
02:45:40,547 --> 02:45:42,916
TIME OF STARTING ART AND THE

4669
02:45:42,916 --> 02:45:48,188
NUMBER OF EXPRESSING CELLS

4670
02:45:48,188 --> 02:45:49,623
PREDICTS HOW MANY INFECTED CELLS

4671
02:45:49,623 --> 02:45:53,560
WILL BE PRODUCING SOME VIRIONS

4672
02:45:53,560 --> 02:45:57,064
AFTER LONG-TERM ART.

4673
02:45:57,064 --> 02:46:01,768
AND THIS INITIAL EVIDENCE, AND

4674
02:46:01,768 --> 02:46:05,806
JOHN LOW PRESSUR LEE HAS SIMILA,

4675
02:46:05,806 --> 02:46:07,975
THAT THE LEVEL OF VIREMIA OR ITS

4676
02:46:07,975 --> 02:46:09,109
PRESENCE PREDICTS THE TIME TO

4677
02:46:09,109 --> 02:46:09,643
REBOUND.

4678
02:46:09,643 --> 02:46:11,712
THERE ARE MANY IMMUNOLOGIC

4679
02:46:11,712 --> 02:46:14,881
FACTORS THAT ADD NOISE TO THAT.

4680
02:46:14,881 --> 02:46:17,517
THE CORRELATION IS BEST IN

4681
02:46:17,517 --> 02:46:20,120
INDIVIDUALS WHO ARE TREATED

4682
02:46:20,120 --> 02:46:22,422
EARLY, BEFORE A BROAD

4683
02:46:22,422 --> 02:46:23,724
IMMUNOLOGIC RESPONSE IS

4684
02:46:23,724 --> 02:46:23,991
GENERATED.

4685
02:46:23,991 --> 02:46:26,593
>> SO JUST TO FOLLOW UP ON
THAT,

4686
02:46:26,593 --> 02:46:27,694
JOHN, SOMETHING I NEVER COULD

4687
02:46:27,694 --> 02:46:30,530
QUITE UNDERSTAND IS WHY DOES

4688
02:46:30,530 --> 02:46:31,798
TREATMENT FOR 10 YEARS OR 20

4689
02:46:31,798 --> 02:46:34,468
YEARS NOT CHANGE THE VIRAL LOAD

4690
02:46:34,468 --> 02:46:34,901
SET POINT?

4691
02:46:34,901 --> 02:46:36,970
YOU KNOW, PEAK VIREMIA IS

4692
02:46:36,970 --> 02:46:39,406
USUALLY WHERE YOU STARTED OUT.

4693
02:46:39,406 --> 02:46:42,042
SO IT WOULD SUGGEST -- YOU'RE

4694
02:46:42,042 --> 02:46:44,845
SAYING THERE MIGHT BE SOME FIXED

4695
02:46:44,845 --> 02:46:45,979
BURSAES THAT'S DRIVING THAT

4696
02:46:45,979 --> 02:46:46,513
REBOUND.

4697
02:46:46,513 --> 02:46:48,582
SO FOR EXAMPLE, IN THE

4698
02:46:48,582 --> 02:46:50,884
MISSISSIPPI BABY AT REBOUND,

4699
02:46:50,884 --> 02:46:52,219
RECEIPT BOUND PEAK VIREMIA WAS

4700
02:46:52,219 --> 02:46:53,720
VERY SIMILAR TO THE TIME OF

4701
02:46:53,720 --> 02:46:54,621
DIAGNOSIS.

4702
02:46:54,621 --> 02:46:56,290
AND THAT'S BEEN SHOWN RELIABLY

4703
02:46:56,290 --> 02:46:57,658
IN THE FIELD, THAT WE DON'T

4704
02:46:57,658 --> 02:47:02,062
REALLY ALTER THAT PATTERN OF

4705
02:47:02,062 --> 02:47:03,363
REBOUND WITHOUT

4706
02:47:03,363 --> 02:47:04,097
IMMUNOTHERAPEUTICS OBVIOUSLY.

4707
02:47:04,097 --> 02:47:08,735
>> YEAH, I MEAN, I GUESS
IF --

4708
02:47:08,735 --> 02:47:11,038
ART DOESN'T ALTER THE ABILITY TO

4709
02:47:11,038 --> 02:47:11,805
CONTROL, RIGHT?

4710
02:47:11,805 --> 02:47:16,843
IT CONTROLS VIREMIA AND VIRUS

4711
02:47:16,843 --> 02:47:17,144
PRODUCTION.

4712
02:47:17,144 --> 02:47:19,680
SO WITHOUT AN ADDITIONAL -- IN

4713
02:47:19,680 --> 02:47:22,182
SOME -- IT'S HETEROGENEOUS BUT

4714
02:47:22,182 --> 02:47:23,717
THE AVERAGE IS THAT IT DOESN'T

4715
02:47:23,717 --> 02:47:27,220
AFFECT IMMUNE CONTROL.

4716
02:47:27,220 --> 02:47:29,189
SO THUS THE NEED FOR

4717
02:47:29,189 --> 02:47:30,357
INTERVENTIONS AS YOU SUGGESTED.

4718
02:47:30,357 --> 02:47:32,359
>> AND TO CLARIFY THE
STUDIES

4719
02:47:32,359 --> 02:47:33,560
THAT I PRESENTED REALLY JUST

4720
02:47:33,560 --> 02:47:35,195
LOOKED AT CORRELATES OF TIME TO

4721
02:47:35,195 --> 02:47:36,063
VIRAL REBOUND.

4722
02:47:36,063 --> 02:47:37,698
ALL OF THOSE EARLY ATI STUDIES,

4723
02:47:37,698 --> 02:47:39,633
WE STARTED PEOPLE BACK ON ART AS

4724
02:47:39,633 --> 02:47:42,436
SOON AS THEY HIT THEIR FIRST

4725
02:47:42,436 --> 02:47:46,840
INSTANCE OF 1,000 COPIES PER ML

4726
02:47:46,840 --> 02:47:47,574
IN PERIPHERAL BLOOD.

4727
02:47:47,574 --> 02:47:48,842
SO THAT'S WHERE TYING IN THE

4728
02:47:48,842 --> 02:47:50,010
EARLIER QUESTION, ALL OF THE

4729
02:47:50,010 --> 02:47:51,845
WORK WITH OUR COMMUNITIES TO

4730
02:47:51,845 --> 02:47:53,046
UNDERSTAND THE ACCEPTABILITY OF

4731
02:47:53,046 --> 02:47:54,915
BEING WILLING TO GO LONGER,

4732
02:47:54,915 --> 02:47:57,684
WHICH THEY GENERALLY ARE, WOULD

4733
02:47:57,684 --> 02:47:59,820
HELP US ANSWER THOSE QUESTIONS

4734
02:47:59,820 --> 02:48:00,754
IN FUTURE STUDIES.

4735
02:48:00,754 --> 02:48:01,588
>> OKAY.

4736
02:48:01,588 --> 02:48:02,823
ONE FINAL QUICK QUESTION, CAN

4737
02:48:02,823 --> 02:48:03,790
YOU STATE YOUR NAME, PLEASE?

4738
02:48:03,790 --> 02:48:04,324
>> HI.

4739
02:48:04,324 --> 02:48:05,425
MY NAME IS MADISON.

4740
02:48:05,425 --> 02:48:07,294
I'M A POSTBAC HERE AT THE VRC.

4741
02:48:07,294 --> 02:48:10,464
I HAD A QUESTION FOR DR. BAROUCH

4742
02:48:10,464 --> 02:48:11,665
REGARDING THE MULTIPRONG

4743
02:48:11,665 --> 02:48:14,735
STRATEGY FOR HIV SUPPRESSION IN

4744
02:48:14,735 --> 02:48:15,168
B INFECTED CELLS.

4745
02:48:15,168 --> 02:48:18,338
WOULD THIS BY CHANCE ENHANCE

4746
02:48:18,338 --> 02:48:20,640
POTENTIAL MUTATIONS WITH THE

4747
02:48:20,640 --> 02:48:22,943
INCREASED PRESSURE THE VIRUS IS

4748
02:48:22,943 --> 02:48:24,478
OBSERVING FROM THAT MULTIPRONG

4749
02:48:24,478 --> 02:48:25,145
STRATEGY?

4750
02:48:25,145 --> 02:48:27,447
AND THEN ALSO AS A FOLLOW-UP TO

4751
02:48:27,447 --> 02:48:30,250
THAT, WOULD YOU BE ABLE TO

4752
02:48:30,250 --> 02:48:32,452
UTILIZE YOUR BIOMARKER IN BLOOD

4753
02:48:32,452 --> 02:48:34,421
TO BETTER PROTECT WHEN VIRAL

4754
02:48:34,421 --> 02:48:35,756
REBOUND MIGHT OCCUR WITH THAT AS

4755
02:48:35,756 --> 02:48:36,857
WELL?

4756
02:48:36,857 --> 02:48:40,127
>> THANKS FOR YOUR
QUESTIONS.

4757
02:48:40,127 --> 02:48:41,995
I THINK THAT THERE'S

4758
02:48:41,995 --> 02:48:43,196
CONCEPTUALLY TWO WAYS THAT WE

4759
02:48:43,196 --> 02:48:45,499
AND OTHERS ARE TRYING TO APPLY

4760
02:48:45,499 --> 02:48:46,600
INTERVENTIONS.

4761
02:48:46,600 --> 02:48:49,970
ONE IS DURING A PERIOD OF NO

4762
02:48:49,970 --> 02:48:51,505
VIRUS REPLICATION ON FULL ART

4763
02:48:51,505 --> 02:48:52,506
SUPPRESSION OR AS CLOSE TO THAT

4764
02:48:52,506 --> 02:48:55,008
AS WE CAN GET.

4765
02:48:55,008 --> 02:48:57,077
SUCH AS LONG TERM ART

4766
02:48:57,077 --> 02:48:59,279
SUPPRESSION IN MACAQUES OR

4767
02:48:59,279 --> 02:49:01,448
HUMANS, AND THEN PROVIDING

4768
02:49:01,448 --> 02:49:03,950
ANTIBODIES, VACCINES OR OTHER

4769
02:49:03,950 --> 02:49:04,751
INTERVENTIONS.

4770
02:49:04,751 --> 02:49:05,719
IN THAT SETTING, I THINK THAT

4771
02:49:05,719 --> 02:49:07,487
THE CHANCE OF MUTATIONS IS

4772
02:49:07,487 --> 02:49:08,789
RELATIVELY LOW.

4773
02:49:08,789 --> 02:49:10,323
BECAUSE THERE IS NO ONGOING

4774
02:49:10,323 --> 02:49:13,593
VIRUS REPLICATION.

4775
02:49:13,593 --> 02:49:14,494
THE SECOND WAY THAT PEOPLE ARE

4776
02:49:14,494 --> 02:49:17,998
LOOKING AT INTERVENTIONS IS TO

4777
02:49:17,998 --> 02:49:21,168
APPLY THEM EITHER AT THE TIME OF

4778
02:49:21,168 --> 02:49:22,035
ART INTERRUPTION OR SHORTLY

4779
02:49:22,035 --> 02:49:23,570
BEFORE OR SHORTLY AFTER.

4780
02:49:23,570 --> 02:49:28,308
IF THERE IS VIRAL REBOUND IN THE

4781
02:49:28,308 --> 02:49:30,277
CONTEXT OF LEVELS OF BROADLY

4782
02:49:30,277 --> 02:49:31,578
NEUTRALIZING ANTIBODIES OR OTHER

4783
02:49:31,578 --> 02:49:33,647
IMMUNE INTERVENTIONS, THEN I DO

4784
02:49:33,647 --> 02:49:40,987
THINK THAT THERE IS A CHANCE, IN

4785
02:49:40,987 --> 02:49:43,190
SOME CASES LIKELIHOOD TO DEVELOP

4786
02:49:43,190 --> 02:49:44,191
RESISTANCE.

4787
02:49:44,191 --> 02:49:44,958
SO I THINK THE ANSWER TO YOUR

4788
02:49:44,958 --> 02:49:46,259
QUESTION IS PROBABLY DEPENDENT

4789
02:49:46,259 --> 02:49:47,260
ON WHEN INTERVENTIONS ARE

4790
02:49:47,260 --> 02:49:47,928
APPLIED.

4791
02:49:47,928 --> 02:49:49,262
IF THEY'RE APPLIED IN THE

4792
02:49:49,262 --> 02:49:51,097
SETTING OF ONGOING VIRUS

4793
02:49:51,097 --> 02:49:52,199
REPLICATION, THEN SURE, THERE

4794
02:49:52,199 --> 02:49:53,934
COULD BE DEVELOPMENT OF

4795
02:49:53,934 --> 02:49:54,234
RESISTANCE.

4796
02:49:54,234 --> 02:49:55,368
IF THEY'RE APPLIED DURING A

4797
02:49:55,368 --> 02:49:57,671
PERIOD OF NO VIRUS REPLICATION,

4798
02:49:57,671 --> 02:50:00,173
THEN AT LEAST THEORETICALLY WE

4799
02:50:00,173 --> 02:50:01,508
WOULD NOT EXPECT A LOT OF

4800
02:50:01,508 --> 02:50:02,075
RESISTANCE.

4801
02:50:02,075 --> 02:50:05,645
AND SORRY, I FORGOT YOUR SECOND

4802
02:50:05,645 --> 02:50:05,912
QUESTION.

4803
02:50:05,912 --> 02:50:07,214
>>  FOLLOWING UP ON WHEN
YOU

4804
02:50:07,214 --> 02:50:10,150
COULD BETTER PREDICT REBOUND

4805
02:50:10,150 --> 02:50:14,554
USING THAT MULTIPRONGED APPROACH

4806
02:50:14,554 --> 02:50:16,723
UTILIZING YOUR BLOOD BIOMARKER

4807
02:50:16,723 --> 02:50:18,558
FOR THAT.

4808
02:50:18,558 --> 02:50:20,694
>> SO THOSE THAT WE
RECENTLY

4809
02:50:20,694 --> 02:50:21,928
PUBLISHED ARE FOR A VERY NARROW

4810
02:50:21,928 --> 02:50:26,933
INDICATION, WHICH WAS EXTREMELY

4811
02:50:26,933 --> 02:50:29,936
EARLY ART INITIATION IN MACAQUES

4812
02:50:29,936 --> 02:50:31,671
PREVIREMIA, SO ESSENTIALLY DAY

4813
02:50:31,671 --> 02:50:32,873
ONE, DAY TWO, DAY THREE.

4814
02:50:32,873 --> 02:50:35,141
SO IT'S A VERY UNIQUE SITUATION,

4815
02:50:35,141 --> 02:50:37,043
AND I THINK, THEREFORE, THE

4816
02:50:37,043 --> 02:50:39,779
GENERALIZABILITY OF THOSE

4817
02:50:39,779 --> 02:50:41,515
BIOMARKERS, WHICH ARE

4818
02:50:41,515 --> 02:50:42,315
ESSENTIALLY BIOMARKERS OF

4819
02:50:42,315 --> 02:50:44,284
INFECTION, BECAUSE WE'RE PRETTY

4820
02:50:44,284 --> 02:50:46,453
CERTAIN THAT HALF THE ANIMALS

4821
02:50:46,453 --> 02:50:47,854
THAT DIDN'T REBOUND, THEY

4822
02:50:47,854 --> 02:50:48,455
WEREN'T CURED, THEY WERE

4823
02:50:48,455 --> 02:50:50,090
ACTUALLY NEVER INFECTED.

4824
02:50:50,090 --> 02:50:52,526
SO THERE'S SORT OF BIOMARKERS OF

4825
02:50:52,526 --> 02:50:53,493
OCCULT INFECTION, WHEN HALF THE

4826
02:50:53,493 --> 02:50:54,728
ANIMALS ARE INFECTED AND HALF

4827
02:50:54,728 --> 02:50:57,330
ARE NOT, AND YOU DON'T KNOW

4828
02:50:57,330 --> 02:50:58,532
WHICH IS WHICH.

4829
02:50:58,532 --> 02:50:59,599
SO WHETHER THEY'RE APPLICABLE TO

4830
02:50:59,599 --> 02:51:01,835
A SETTING OF EVERYONE BEING

4831
02:51:01,835 --> 02:51:04,571
INFECTED AND LOOKING FOR A

4832
02:51:04,571 --> 02:51:05,071
THERAPEUTIC EFFECT OF AN

4833
02:51:05,071 --> 02:51:06,740
INTERVENTION, I WOULDN'T MAKE

4834
02:51:06,740 --> 02:51:08,608
THAT JUMP.

4835
02:51:08,608 --> 02:51:10,377
WE ARE ACTUALLY LOOKING THROUGH

4836
02:51:10,377 --> 02:51:12,045
THIS PROGRAM AND OTHERS AT

4837
02:51:12,045 --> 02:51:13,013
BIOMARKERS IN A MORE GENERAL

4838
02:51:13,013 --> 02:51:13,446
SENSE.

4839
02:51:13,446 --> 02:51:17,050
SO I GUESS I WOULD SAY THAT THE

4840
02:51:17,050 --> 02:51:20,987
PUBLISHED DATA IS FOR A VERY,

4841
02:51:20,987 --> 02:51:23,690
VERY SPECIFIC INDICATION, AND WE

4842
02:51:23,690 --> 02:51:25,492
HAVE NOT PROVEN AND WOULD HE

4843
02:51:25,492 --> 02:51:27,327
PROBABLY WOULDN'T EVEN

4844
02:51:27,327 --> 02:51:28,028
ANTICIPATE THAT TO BE

4845
02:51:28,028 --> 02:51:29,129
GENERALIZABLE FOR INTERVENTIONAL

4846
02:51:29,129 --> 02:51:29,729
TYPE APPROACHES.

4847
02:51:29,729 --> 02:51:30,063
>> THANK YOU.

4848
02:51:30,063 --> 02:51:33,066
>> OKAY, THANK YOU VERY
MUCH.

4849
02:51:33,066 --> 02:51:38,872
, I4C.

4850
02:51:38,872 --> 02:51:40,073
I'M HANDING IT OVER TO MY

4851
02:51:40,073 --> 02:51:41,141
COLLEAGUE TO MAKE SOME

4852
02:51:41,141 --> 02:51:41,641
ANNOUNCEMENTS.

4853
02:51:41,641 --> 02:51:42,943
>> THANKS A LOT.

4854
02:51:42,943 --> 02:51:45,045
I THINK WE JUST GO FOR THE

4855
02:51:45,045 --> 02:51:45,445
POSTER SESSION.

4856
02:51:45,445 --> 02:51:47,113
I JUST WANT TO REMIND YOU THERE

4857
02:51:47,113 --> 02:51:49,182
ARE SOME POSTERS IN THE BALCONY,

4858
02:51:49,182 --> 02:51:53,520
IF PEOPLE -- ADDITIONAL POSTERS,

4859
02:51:53,520 --> 02:51:54,354
AND THEN WE COME BACK AFTER

4860
02:51:54,354 --> 02:51:56,089
LUNCH AT 1:40 P.M., SO I WOULD

4861
02:51:56,089 --> 02:51:58,725
REQUEST YOU TO PLEASE COME A FEW

4862
02:51:58,725 --> 02:51:59,726
MINUTES EARLIER SO WE CAN GET

4863
02:51:59,726 --> 02:52:00,393
STARTED ON TIME.

4864
02:52:00,393 --> 02:52:09,169
THANK YOU.

4865
02:52:43,145 --> 02:52:43,912
 A LITTLE BIT OF A LEARNING

4866
02:52:43,912 --> 02:52:46,315
CURVE, BUT I THINK WE'VE REALLY

4867
02:52:46,315 --> 02:52:47,416
HIT OUR STRIDE AND YOU'LL SEE

4868
02:52:47,416 --> 02:52:49,384
SOME OF THE GREAT WORK THAT OUR

4869
02:52:49,384 --> 02:52:52,788
TEAM MEMBERS ARE DOING.

4870
02:52:52,788 --> 02:52:54,957
SO I'M RUNNING THIS

4871
02:52:54,957 --> 02:52:59,761
COLLABORATORY IN COLLABORATION

4872
02:52:59,761 --> 02:53:03,632
WI,JUST A SHOUT OUT TO JEFF TAIR

4873
02:53:03,632 --> 02:53:06,101
TWO COULDN'T BE HERE BECAUSE OF

4874
02:53:06,101 --> 02:53:07,202
COVID, APPARENTLY HE GOT IT

4875
02:53:07,202 --> 02:53:08,971
STANDING IN LINE FOR HIS BOOSTER

4876
02:53:08,971 --> 02:53:15,844
SHOT, SO THERE YOU GO.

4877
02:53:15,844 --> 02:53:17,379
SO WE'RE GOING TO -- REALLY,

4878
02:53:17,379 --> 02:53:19,014
JEFF HAS BEEN DOING AN AMAZING

4879
02:53:19,014 --> 02:53:20,215
JOB AND WE'VE BEEN LEARNING A

4880
02:53:20,215 --> 02:53:22,184
LOT FROM HUM IN THE COMMUNITY

4881
02:53:22,184 --> 02:53:23,285
ENGAGEMENT SIDE.

4882
02:53:23,285 --> 02:53:24,953
OUR SCIENTIFIC ADVISORY BOARD

4883
02:53:24,953 --> 02:53:27,122
JUST HATS OFF TO THEM FOR GIVING

4884
02:53:27,122 --> 02:53:29,458
US AMAZING FEEDBACK, AND I

4885
02:53:29,458 --> 02:53:30,726
COULDN'T HOPE FOR A BETTER TEAM

4886
02:53:30,726 --> 02:53:33,695
OF SCIENTISTS TO WORK WITH TO

4887
02:53:33,695 --> 02:53:38,066
LEAD THIS EFFORT.

4888
02:53:38,066 --> 02:53:42,871
SO AS MENTIONED, OUR NAME IS RID

4889
02:53:42,871 --> 02:53:45,273
HIV, WHICH STANDS FOR REVERSING

4890
02:53:45,273 --> 02:53:49,578
IMMUNE DYSFUNCTION TO ACHIEVE A

4891
02:53:49,578 --> 02:53:49,778
CURE.

4892
02:53:49,778 --> 02:53:52,080
SO THE UNDERLYING PREMISE REALLY

4893
02:53:52,080 --> 02:53:54,149
IS THAT WHEN YOU HAVE AN ACUTE

4894
02:53:54,149 --> 02:53:57,986
INFECTION, THE INSULT ONTO THE

4895
02:53:57,986 --> 02:53:58,954
IMMUNE SYSTEM PRECLUDES THE

4896
02:53:58,954 --> 02:54:03,659
ABILITY OF THE IMMUNE SYSTEM TO

4897
02:54:03,659 --> 02:54:07,062
CONTROL VIREMIA DURING A CHRONIC

4898
02:54:07,062 --> 02:54:08,463
PHASE SO WE'RE TRYING TO

4899
02:54:08,463 --> 02:54:12,200
UNDERSTAND WHAT THOSE ARE AND

4900
02:54:12,200 --> 02:54:13,402
DEVELOP APPROACHES TO REVERSE

4901
02:54:13,402 --> 02:54:13,935
THEM.

4902
02:54:13,935 --> 02:54:17,873
AND WE'RE SPLITTING INTO 3RFs

4903
02:54:17,873 --> 02:54:18,774
AS MOST ARE.

4904
02:54:18,774 --> 02:54:21,076
THE FIRST RF IS REALLY OUR

4905
02:54:21,076 --> 02:54:25,213
EXPLORATORY RF.

4906
02:54:25,213 --> 02:54:27,182
A LITTLE ABOUT THE ROLE OF THE

4907
02:54:27,182 --> 02:54:29,918
HOST MICROBIOME ON INNATE

4908
02:54:29,918 --> 02:54:31,286
IMMUNITY AND THE ADAPTIVE

4909
02:54:31,286 --> 02:54:33,288
INTERFACE AND REALLY A NICE

4910
02:54:33,288 --> 02:54:36,925
STORY ON BILE ACIDS AND THEIR

4911
02:54:36,925 --> 02:54:39,428
IMPACT ON INNATE DYSFUNCTION AND

4912
02:54:39,428 --> 02:54:40,529
HIV PERSISTENCE.

4913
02:54:40,529 --> 02:54:41,830
THEY'RE ALSO USING A NUMBER OF

4914
02:54:41,830 --> 02:54:45,767
REALLY LEADING EDGE OMICS

4915
02:54:45,767 --> 02:54:48,370
EFFORTS, MULTI-SCALE OMICS TO

4916
02:54:48,370 --> 02:54:51,573
CHARACTERIZE THE COHORT THAT

4917
02:54:51,573 --> 02:54:53,842
JAVIER AND OTHERS HAVE

4918
02:54:53,842 --> 02:54:54,943
ESTABLISHED IN PEOPLE LIVING

4919
02:54:54,943 --> 02:54:56,712
WITH HIV WITH VERY HIGH AND VERY

4920
02:54:56,712 --> 02:54:59,981
LOW VIRAL RESERVOIRS TO SEE IF

4921
02:54:59,981 --> 02:55:03,285
THERE ARE REALLY IMMUNE LOGICAL

4922
02:55:03,285 --> 02:55:05,487
CORRELATES IN THE LOW RESERVOIR

4923
02:55:05,487 --> 02:55:06,988
INDIVIDUALS THAT WE CAN EXPLOIT

4924
02:55:06,988 --> 02:55:09,391
TO UNDERSTAND BOTH RESERVOIR

4925
02:55:09,391 --> 02:55:13,562
SEEDING AND CONTROL OF VIREMIA.

4926
02:55:13,562 --> 02:55:17,599
RF2 IS REALLY FOCUSING ON THE

4927
02:55:17,599 --> 02:55:22,003
RESTORATION TO HELP PRIME

4928
02:55:22,003 --> 02:55:26,374
CD8 CELLS TO CLEAR HIV INFECTED

4929
02:55:26,374 --> 02:55:28,944
CELLS DURING OR AFTER ATI, AND

4930
02:55:28,944 --> 02:55:30,378
SO A LOT OF THESE OMICS

4931
02:55:30,378 --> 02:55:33,882
APPROACHES THAT YOU'LL HEAR

4932
02:55:33,882 --> 02:55:36,718
ABOUT IS ALSO BEING USED TO DO

4933
02:55:36,718 --> 02:55:39,855
MULTI-SCALE ANALYSIS LOOKING AT

4934
02:55:39,855 --> 02:55:41,022
DIFFERENT KINETICS OF VIRAL

4935
02:55:41,022 --> 02:55:42,324
REBOUND AFTER ATI, AND THEN

4936
02:55:42,324 --> 02:55:43,859
YOU'LL HEAR ABOUT A COUPLE

4937
02:55:43,859 --> 02:55:44,626
PHARMACOLOGICAL APPROACHES

4938
02:55:44,626 --> 02:55:47,262
INCLUDING AN OFF THE SHELF TSCM

4939
02:55:47,262 --> 02:55:49,131
PRODUCT THAT'S BEEN KNOCKED OUT

4940
02:55:49,131 --> 02:55:54,269
FOR CCR5 TO PROVIDE CD4 HELP AND

4941
02:55:54,269 --> 02:55:55,570
TGF BETA INHIBITOR WHICH WE'VE

4942
02:55:55,570 --> 02:56:00,075
BEEN WORKING ON WITH MERCK TO

4943
02:56:00,075 --> 02:56:04,212
MOVE INTO NHP STUDIES EITHER

4944
02:56:04,212 --> 02:56:06,615
ALONE OR IN CONJUNCTION WITH

4945
02:56:06,615 --> 02:56:08,717
PD-1 ANTIBODIES, WHICH EXTENDS

4946
02:56:08,717 --> 02:56:10,452
THE WORK THAT RAFIQ AND HIS

4947
02:56:10,452 --> 02:56:11,419
GROUP HAVE BEEN DOING IN THAT

4948
02:56:11,419 --> 02:56:15,056
AREA.

4949
02:56:15,056 --> 02:56:17,659
RF3 FOCUSES MORE ON THE

4950
02:56:17,659 --> 02:56:19,761
CLASSICAL LATENCY REACTIVATION

4951
02:56:19,761 --> 02:56:23,131
AND KILL STRATEGIES, SO MY GROUP

4952
02:56:23,131 --> 02:56:25,767
ALONG WITH LARS IS WORKING ON

4953
02:56:25,767 --> 02:56:26,735
IMPROVING BUILDING NEXT

4954
02:56:26,735 --> 02:56:28,370
GENERATION SMACK MIMETICS, SO

4955
02:56:28,370 --> 02:56:30,772
INSTEAD OF TRYING TO TAKE CANCER

4956
02:56:30,772 --> 02:56:33,408
DRUGS AND SHOVE THEM INTO AN HIV

4957
02:56:33,408 --> 02:56:35,043
CURE REGIMEN, WE'RE DOING THE

4958
02:56:35,043 --> 02:56:36,678
CHEMISTRY FROM THE BEGINNING TO

4959
02:56:36,678 --> 02:56:40,415
DEVELOP A BESPOKE LATENCY

4960
02:56:40,415 --> 02:56:42,384
REVERSAL AGENT FOR HIV AS WELL

4961
02:56:42,384 --> 02:56:44,686
AS TRYING TO DEVELOP NOVEL

4962
02:56:44,686 --> 02:56:47,422
CLASSES OF LATENCY REVERSALS

4963
02:56:47,422 --> 02:56:49,491
USING HIGH THROUGHPUT SCREENING

4964
02:56:49,491 --> 02:56:50,926
AND PRIMARY PATIENT DERIVED

4965
02:56:50,926 --> 02:56:51,993
CELLS.

4966
02:56:51,993 --> 02:56:55,330
KILL STRATEGIES, YOU'LL HEAR,

4967
02:56:55,330 --> 02:56:57,699
CRISPR NK RECRUITMENT AND

4968
02:56:57,699 --> 02:56:59,868
SELL-BASED BNABs, AND THINK

4969
02:56:59,868 --> 02:57:01,002
ONE OF THE MORE ECK SIGHT THINGS

4970
02:57:01,002 --> 02:57:06,141
WE'RE DOING IS WORKING TO USE

4971
02:57:06,141 --> 02:57:07,008
MATH MODELING TO INTEGRATE ALL

4972
02:57:07,008 --> 02:57:09,110
OF THIS DATA AND TRY TO HAVE

4973
02:57:09,110 --> 02:57:14,583
SOME PREDICTIVE CAPACITY TO TELF

4974
02:57:14,583 --> 02:57:17,219
IMMUNE MODULATORS, LRAs AND

4975
02:57:17,219 --> 02:57:21,823
KILL STRATEGIES MIGHT BE MOST

4976
02:57:21,823 --> 02:57:24,860
EFFICIENT IN REDUCING THE

4977
02:57:24,860 --> 02:57:26,428
RESERVOIR AND ESTABLISHING

4978
02:57:26,428 --> 02:57:32,834
CONTROL OF VIREMIA.

4979
02:57:32,834 --> 02:57:34,369
SEW THE WAY WE DESIGNED OUR

4980
02:57:34,369 --> 02:57:36,438
GRANT, WE HAVE TWO TRANCHES OF

4981
02:57:36,438 --> 02:57:37,672
NHP STUDIES.

4982
02:57:37,672 --> 02:57:38,707
THE FIRST ONE WE'RE KIND OF

4983
02:57:38,707 --> 02:57:40,175
COMING UP TO AT THE END OF YEAR

4984
02:57:40,175 --> 02:57:44,112
TWO, AND SO WE'RE PROPOSING

4985
02:57:44,112 --> 02:57:46,181
RIGHT NOW THREE DIFFERENT

4986
02:57:46,181 --> 02:57:52,187
INTERVENTIONS SO ONE IS THE CCR.

4987
02:57:52,187 --> 02:57:53,855
YOU'LL HEAR FROM RAFIQ.

4988
02:57:53,855 --> 02:57:55,790
THE SECOND IS WITH TGF

4989
02:57:55,790 --> 02:57:57,592
INHIBITORS PLUS OR MINUS PD-1

4990
02:57:57,592 --> 02:58:01,830
AND THE THIRD IS USING NOVEL

4991
02:58:01,830 --> 02:58:03,265
SMACK MIMETICS THAT WE'VE

4992
02:58:03,265 --> 02:58:05,467
DEVELOPED IN THE GROUP TO LOOK

4993
02:58:05,467 --> 02:58:12,540
FOR LATENCY REVERSAL.

4994
02:58:12,540 --> 02:58:14,509
THIS IS MEANT TO BE A VERY IT

4995
02:58:14,509 --> 02:58:16,144
RIFF PROCESS WHERE ALL OF OUR

4996
02:58:16,144 --> 02:58:18,546
DATA WE'RE GENERATING GETS FED

4997
02:58:18,546 --> 02:58:21,683
INTO THESE INSILICO MODELS AND

4998
02:58:21,683 --> 02:58:24,152
THEN WILL BE USED TO REALLY

4999
02:58:24,152 --> 02:58:25,887
DRIVE WHAT THE EXPERIMENTS AND

5000
02:58:25,887 --> 02:58:28,523
THE INTERVENTIONS WE'RE GOING TO

5001
02:58:28,523 --> 02:58:31,526
FOCUS ON IN THE THREE PRIME END

5002
02:58:31,526 --> 02:58:32,027
OF THE GRANT.

5003
02:58:32,027 --> 02:58:33,528
SO WITH THAT, I'M GOING TO HAND

5004
02:58:33,528 --> 02:58:37,265
THINGS OVER TO HEAR ABOUT THE

5005
02:58:37,265 --> 02:58:46,241
WORK GOING ON IN RF 1.

5006
02:58:46,241 --> 02:58:49,611
>> I WILL FOCUS ON THE RF

5007
02:58:49,611 --> 02:58:54,316
1 UPDATES FOR OUR MDC.

5008
02:58:54,316 --> 02:58:59,587
THIS IS LED BY RAFICK AND THE

5009
02:58:59,587 --> 02:59:03,091
BACKBONE IS REALLY THE STATEMENT

5010
02:59:03,091 --> 02:59:04,159
THAT YOU ARE WHAT YOU EAT, AND

5011
02:59:04,159 --> 02:59:07,595
WHAT YOU EAT DRIVES YOUR IMMUNE

5012
02:59:07,595 --> 02:59:08,863
DYSFUNCTION IN HIV PERSISTENCE.

5013
02:59:08,863 --> 02:59:09,965
TO ADDRESS THAT POINT, WE HAVE

5014
02:59:09,965 --> 02:59:13,601
BEEN WORKING WITH GROUPS ACROSS

5015
02:59:13,601 --> 02:59:16,071
EUROPE AND THE U.S.

5016
02:59:16,071 --> 02:59:20,475
WE HAVE JAVIER AND MARIA IN

5017
02:59:20,475 --> 02:59:30,986
BARCELONA, ALL OF US AT EMORY.

5018
02:59:31,586 --> 02:59:35,023
THEN WE ARE WORKING WITH MERCK

5019
02:59:35,023 --> 02:59:44,199
AND AS SUMIT MENTIONED, IN

5020
02:59:44,199 --> 02:59:45,934
LOS ALAMOS.

5021
02:59:45,934 --> 02:59:49,471
NOW, THE SUMMARY SLIDE WHICH IS

5022
02:59:49,471 --> 02:59:50,872
THE NEXT SLIDE IS SORT OF

5023
02:59:50,872 --> 02:59:51,639
CHARACTERIZED WITHIN THIS

5024
02:59:51,639 --> 02:59:52,273
CARTOON HERE.

5025
02:59:52,273 --> 02:59:53,808
THE KEY QUESTION THAT WE WANT TO

5026
02:59:53,808 --> 02:59:56,878
ANSWER IS HOW DO THE METABOLITES

5027
02:59:56,878 --> 03:00:03,118
IMPACT THE HOST IMMUNE SYSTEM.

5028
03:00:03,118 --> 03:00:05,186
THEY CAN BE DIET RELATED, THEY

5029
03:00:05,186 --> 03:00:10,425
CAN BE METABOLIZED BY THE

5030
03:00:10,425 --> 03:00:13,828
MICROBIOME -- IN THE INNATE AND

5031
03:00:13,828 --> 03:00:15,163
ADAPTIVE IMMUNE SYSTEM THAT GET

5032
03:00:15,163 --> 03:00:18,033
ALTERED BY THIS MICROBIAL

5033
03:00:18,033 --> 03:00:20,935
METABALOME AXE AND LOOK AT HOW

5034
03:00:20,935 --> 03:00:26,508
THE CYTOKINE RESPONSES THAT

5035
03:00:26,508 --> 03:00:27,942
RESULT, PERSISTENCE OF THE HIV

5036
03:00:27,942 --> 03:00:28,710
REST VOYEUR.

5037
03:00:28,710 --> 03:00:30,578
THAT'S SUMMARIZED IN THIS SLIDE

5038
03:00:30,578 --> 03:00:31,212
HERE.

5039
03:00:31,212 --> 03:00:33,748
THE MAIN QUESTION -- ON THE

5040
03:00:33,748 --> 03:00:35,283
IMMUNE SYSTEM AND THE RESERVOIR,

5041
03:00:35,283 --> 03:00:39,087
AND WHAT WE HAVE DONE SO FAR IS

5042
03:00:39,087 --> 03:00:44,559
ACCRUED SAMPLES WITHIN THE

5043
03:00:44,559 --> 03:00:45,860
TREATMENT INTERRUPTION AND WE

5044
03:00:45,860 --> 03:00:48,129
HAVE LOOKED AT WHAT SORT OF

5045
03:00:48,129 --> 03:00:49,531
IMMUNE RESPONSES DISTINGUISH

5046
03:00:49,531 --> 03:00:51,933
THOSE PEOPLE AT HIGH RESERVOIR

5047
03:00:51,933 --> 03:00:53,101
VERSUS LOW RESERVOIR, AND WE

5048
03:00:53,101 --> 03:00:54,769
HAVE REALLY IDENTIFIED TWO

5049
03:00:54,769 --> 03:00:56,738
FAMILIES OF METABOLITE, THE

5050
03:00:56,738 --> 03:00:59,240
SHORT CHAIN FATTY ACIDS AND THE

5051
03:00:59,240 --> 03:01:01,109
BILE ACIDS AS DRIVERS OF IMMUNE

5052
03:01:01,109 --> 03:01:02,243
DYSFUNCTION AND PERSISTENCE OF

5053
03:01:02,243 --> 03:01:04,846
THE RESERVOIR, AND THIS IS

5054
03:01:04,846 --> 03:01:07,115
IMPORTANT BECAUSE WE WANT TO BE

5055
03:01:07,115 --> 03:01:08,883
ABLE TO MAKE THERAPEUTICS THAT

5056
03:01:08,883 --> 03:01:12,187
WOULD NOT ONLY CURB THE HIV

5057
03:01:12,187 --> 03:01:15,223
RESERVOIR BUT ALSO REJUVENATE

5058
03:01:15,223 --> 03:01:17,959
THE METABOLIC RESPONSE AND LEAD

5059
03:01:17,959 --> 03:01:20,795
TO OVERALL HEALTH IMPROVEMENT.

5060
03:01:20,795 --> 03:01:22,864
NOW AS I WAS SAYING, THE COHORTS

5061
03:01:22,864 --> 03:01:25,733
THAT WE HAVE RECRUITED, THEY

5062
03:01:25,733 --> 03:01:30,638
COME FROM EMORY IN ATLANTA AND

5063
03:01:30,638 --> 03:01:32,173
IN BOSTON, BUT WE ALSO HAVE

5064
03:01:32,173 --> 03:01:36,111
COHORT IN BARCELONA AND GENT

5065
03:01:36,111 --> 03:01:39,948
WITH JAVIER'S GROUP.

5066
03:01:39,948 --> 03:01:43,218
THESE COHORTS ARE EITHER

5067
03:01:43,218 --> 03:01:45,086
RETROSPECTIVE -- OR TREATED

5068
03:01:45,086 --> 03:01:48,590
COHORTS THAT THE DRAWI DURATIONT

5069
03:01:48,590 --> 03:01:50,558
CAN BE AS LONG AS 20 YEARS OR AS

5070
03:01:50,558 --> 03:01:54,496
SHORT AS ACUTE -- WE HAVE A

5071
03:01:54,496 --> 03:01:56,998
COUPLE OF COHORTS WHERE WE HAVE

5072
03:01:56,998 --> 03:01:58,399
ANALYTICAL TREATMENT

5073
03:01:58,399 --> 03:01:59,400
INTERRUPTION WHERE THE

5074
03:01:59,400 --> 03:02:00,268
PARTICIPANTS HAVE BEEN PULLED

5075
03:02:00,268 --> 03:02:04,205
OFF OF ART AND WE GET A CHANCE

5076
03:02:04,205 --> 03:02:06,441
TO LOOK AT THE DURATION TO BILE

5077
03:02:06,441 --> 03:02:09,144
REBOUND AND THE MAGNITUDE OF THE

5078
03:02:09,144 --> 03:02:13,181
VIREMIA UPON ANTIRETROVIRAL

5079
03:02:13,181 --> 03:02:13,748
TREATMENT INTERRUPTION.

5080
03:02:13,748 --> 03:02:15,350
ONE OF THESE COHORT WE WANTED TO

5081
03:02:15,350 --> 03:02:19,954
QUICKLY GO OVER IS CALLED THE

5082
03:02:19,954 --> 03:02:23,358
VOVIRET COHORT IN BARCELONA,

5083
03:02:23,358 --> 03:02:26,928
THIS IS A COHORT OF INDIVIDUALS

5084
03:02:26,928 --> 03:02:28,530
THAT HAVE BEEN ART-SUPPRESSED

5085
03:02:28,530 --> 03:02:30,899
FOR THREE OR MORE YEARS AND THE

5086
03:02:30,899 --> 03:02:32,100
RESERVOIR HAS BEEN QUANTIFIED IN

5087
03:02:32,100 --> 03:02:34,836
THESE PARTICIPANTS.

5088
03:02:34,836 --> 03:02:37,138
YOU CAN SEE ON THE Y AXIS, THE

5089
03:02:37,138 --> 03:02:38,773
RANGE OF THE RESERVOIR ON THE

5090
03:02:38,773 --> 03:02:43,044
LOG SCALE IS ABOUT 3 1/2 LOG

5091
03:02:43,044 --> 03:02:44,045
SCALE.

5092
03:02:44,045 --> 03:02:45,914
SO WITHIN THIS COHORT, THERE ARE

5093
03:02:45,914 --> 03:02:47,782
INDIVIDUALS THAT HAVE VERY HIGH

5094
03:02:47,782 --> 03:02:49,517
VIRAL RESERVOIR, AND THOSE THAT

5095
03:02:49,517 --> 03:02:52,453
HAVE VERY LOW VIRAL RESERVOIR,

5096
03:02:52,453 --> 03:02:53,221
AND ONE OF THE THINGS THAT WE

5097
03:02:53,221 --> 03:02:56,191
ARE DOING IS ATTEMPTING TO

5098
03:02:56,191 --> 03:02:59,561
CHARACTERIZE THE CLINICAL,

5099
03:02:59,561 --> 03:03:01,329
METABOLIC, IMMUNOLOGICAL AND

5100
03:03:01,329 --> 03:03:02,297
METABOLIC OUTCOMES THAT

5101
03:03:02,297 --> 03:03:03,498
DISTINGUISH THIS LOW RESERVOIR

5102
03:03:03,498 --> 03:03:05,266
GROUP FROM THE OTHER

5103
03:03:05,266 --> 03:03:05,567
INDIVIDUALS.

5104
03:03:05,567 --> 03:03:07,335
AND IN AN ATTEMPT TO DO THAT, WE

5105
03:03:07,335 --> 03:03:09,204
HAVE IDENTIFIED A SET OF

5106
03:03:09,204 --> 03:03:11,940
CLINICAL VARIABLES, 18 CLINICAL

5107
03:03:11,940 --> 03:03:13,808
SET FEATURE THAT DISTINGUISHES

5108
03:03:13,808 --> 03:03:16,644
THIS GROUP FROM THE OTHER

5109
03:03:16,644 --> 03:03:17,078
GROUPS.

5110
03:03:17,078 --> 03:03:19,914
NOW THAT'S JUST THE CLINICAL

5111
03:03:19,914 --> 03:03:21,349
OVERVIEW.

5112
03:03:21,349 --> 03:03:23,851
IN ADDITION TO THAT, WE ARE

5113
03:03:23,851 --> 03:03:25,320
DOING ALL OF THESE DIFFERENT

5114
03:03:25,320 --> 03:03:26,788
ASSAYS, BOTH ON THE IMMUNOLOGY

5115
03:03:26,788 --> 03:03:27,889
SIDE AND THE VIROLOGY SIDE.

5116
03:03:27,889 --> 03:03:29,657
IF YOU LOOK AT THE IMMUNOLOGY

5117
03:03:29,657 --> 03:03:31,960
SIDE, WE HAVE ASSAYS THAT ARE

5118
03:03:31,960 --> 03:03:33,461
FAIRLY HIGH THROUGHPUT.

5119
03:03:33,461 --> 03:03:35,563
YOU CAN -- WE RAN ABOUT A COUPLE

5120
03:03:35,563 --> 03:03:37,465
WEEKS AGO A THOUSAND SAMPLES FOR

5121
03:03:37,465 --> 03:03:38,600
PLASMA CYTOKINES.

5122
03:03:38,600 --> 03:03:40,702
THESE ASSAYS DOWN HERE, THEY

5123
03:03:40,702 --> 03:03:42,770
CHARACTERIZE THE SYSTEMIC MILIEU

5124
03:03:42,770 --> 03:03:45,173
AND THEN AS YOU GO UPWARDS AND

5125
03:03:45,173 --> 03:03:47,041
DO FLOW CYTOMETRY AND RNA

5126
03:03:47,041 --> 03:03:48,343
SEQUENCING AND SINGLE CELL

5127
03:03:48,343 --> 03:03:52,046
ASSAYS, YOU GET MORE GRANULARITY

5128
03:03:52,046 --> 03:03:56,217
WITHIN THE CELL LEVEL PATHWAYS.

5129
03:03:56,217 --> 03:03:58,019
ON THE BIOLOGICAL SIDE, THE SAME

5130
03:03:58,019 --> 03:04:00,488
AS IMENT EU NOLG, YOU START OFF

5131
03:04:00,488 --> 03:04:03,992
WITH BROAD VIRAL -- AS TOTAL --

5132
03:04:03,992 --> 03:04:05,393
LEVELS OR VIREMIA LEVELS AND

5133
03:04:05,393 --> 03:04:07,495
THEN YOU MOVE DOWN TO SINGLE

5134
03:04:07,495 --> 03:04:11,266
CELL ASSAYS THAT GIVE YOU

5135
03:04:11,266 --> 03:04:14,836
GRANULARITY INTO THE VIROLOGICAL

5136
03:04:14,836 --> 03:04:15,403
OUTCOMES.

5137
03:04:15,403 --> 03:04:17,205
OUR GOAL IS TO CAPTURE THE

5138
03:04:17,205 --> 03:04:17,905
INTEGRATION, TRANSCRIPTION,

5139
03:04:17,905 --> 03:04:18,906
TRANSLATION AND REPLICATION OF

5140
03:04:18,906 --> 03:04:22,043
THE VIRUS ALONG WITH THE HOST

5141
03:04:22,043 --> 03:04:23,878
METABALOME, THE IMMUNE RESPONSE

5142
03:04:23,878 --> 03:04:26,514
AND THE EPIGENETIC AND

5143
03:04:26,514 --> 03:04:27,982
TRANSCRIPTOME OUTPUT.

5144
03:04:27,982 --> 03:04:32,186
AND WE HAVE BEEN ABLE TO PUSH

5145
03:04:32,186 --> 03:04:33,621
THIS AGENDA FORWARD AT LEAST FOR

5146
03:04:33,621 --> 03:04:38,459
A COUPLE OF OUR COHORTS AND THIS

5147
03:04:38,459 --> 03:04:40,862
SLIDE CHARACTERIZES THE DRIVERS

5148
03:04:40,862 --> 03:04:43,231
OF THE HIGHEST RESERVOIR AT EACH

5149
03:04:43,231 --> 03:04:46,334
ONE OF OUR OMIC LEVELS, SO

5150
03:04:46,334 --> 03:04:48,603
MICROBIOME WISE WE SEE THAT

5151
03:04:48,603 --> 03:04:50,805
LACTOBACILLI DRIVE THE HIGHEST

5152
03:04:50,805 --> 03:04:56,711
REST VOYEUR, DOWNRESERVOIR, THED

5153
03:04:56,711 --> 03:04:59,147
ASSOCIATED SIGNALING IN

5154
03:04:59,147 --> 03:05:00,648
DYSFUNCTIONAL CD4 T-CELLS AS THE

5155
03:05:00,648 --> 03:05:03,151
DRIVER OF OUR HIGHEST RESERVOIR.

5156
03:05:03,151 --> 03:05:05,753
WE HAVE THE EX VIVO CORRELATE TO

5157
03:05:05,753 --> 03:05:08,189
FINISH OFF THE STORIES, WE HAVE

5158
03:05:08,189 --> 03:05:10,258
GONE INTO IN VITRO VALIDATION

5159
03:05:10,258 --> 03:05:10,591
ASSAYS.

5160
03:05:10,591 --> 03:05:12,026
THIS IS AN EXAMPLE OF THE WORK

5161
03:05:12,026 --> 03:05:14,529
THAT WE HAVE BEEN DOING ON THE

5162
03:05:14,529 --> 03:05:16,497
MICROBIOME, GIVEN THAT

5163
03:05:16,497 --> 03:05:18,132
LACTOBACILLI SPECIES CAME UP AS

5164
03:05:18,132 --> 03:05:21,202
A DRIVER OF HIGH RESERVOIR

5165
03:05:21,202 --> 03:05:22,537
HARBORING CELLS IN OUR ASSAYS,

5166
03:05:22,537 --> 03:05:24,839
WE DID DO IN VITRO ASSAYS IN

5167
03:05:24,839 --> 03:05:27,008
COLLABORATION WITH MERCK TO

5168
03:05:27,008 --> 03:05:28,543
UNDERSTAND WHAT LACTOBACILLI

5169
03:05:28,543 --> 03:05:30,178
PROMOTE THE SHORT CHAIN FATTY

5170
03:05:30,178 --> 03:05:33,781
ACIDS THAT DRIVE T-CELL

5171
03:05:33,781 --> 03:05:34,949
DYSFUNCTION AND RESERVOIR

5172
03:05:34,949 --> 03:05:36,084
PERSISTENCE AND WE'VE IDENTIFIED

5173
03:05:36,084 --> 03:05:38,286
THIS GROUP OF LACTOBACILLI,

5174
03:05:38,286 --> 03:05:41,022
THESE ARE RELATIVELY LOW

5175
03:05:41,022 --> 03:05:42,957
ABUNDANCE SPECIES THAT SEEM TO

5176
03:05:42,957 --> 03:05:48,930
PROMOTE THE ACCUMULATION OF

5177
03:05:48,930 --> 03:05:52,500
ALPHA KETOBUTYRATE.

5178
03:05:52,500 --> 03:05:53,901
IN ADDITION TO THE MICROBIOME,

5179
03:05:53,901 --> 03:05:57,438
THE BILE ACID WORK IS

5180
03:05:57,438 --> 03:05:57,872
DEMONSTRATED HERE.

5181
03:05:57,872 --> 03:06:00,842
WE HAVE BEEN LOOKING AT THE

5182
03:06:00,842 --> 03:06:08,916
METABOLITES IN AN UNBIASED WAY,

5183
03:06:08,916 --> 03:06:10,885
TO UNDERSTAND THE BIOLOGY OF

5184
03:06:10,885 --> 03:06:13,087
BILE ACIDS IN RESERVOIR

5185
03:06:13,087 --> 03:06:14,622
PERSISTENCE, WE CONDUCTED AN IN

5186
03:06:14,622 --> 03:06:15,923
VITRO ASSAY WHERE WE DID A

5187
03:06:15,923 --> 03:06:19,560
SCREEN OF 29 DIFFERENT BILE

5188
03:06:19,560 --> 03:06:21,496
ACIDS THAT SPAN PRIMARY AND

5189
03:06:21,496 --> 03:06:22,930
SECONDARY TYPES OF BILE ACIDS

5190
03:06:22,930 --> 03:06:27,402
THAT HAD EITHER NO CONJUGATION,

5191
03:06:27,402 --> 03:06:28,302
GLYCINE TAURINE CONJUGATION AND

5192
03:06:28,302 --> 03:06:31,139
ANY KIND OF SECONDARY

5193
03:06:31,139 --> 03:06:32,006
MODIFICATIONS, AND IN A GIST

5194
03:06:32,006 --> 03:06:33,875
WHAT WE SAW WAS THAT WHENEVER

5195
03:06:33,875 --> 03:06:35,710
YOU INCUBATE YOUR T-CELL WITH A

5196
03:06:35,710 --> 03:06:37,812
PRIMARY BILE ACID, YOU

5197
03:06:37,812 --> 03:06:40,648
UPREGULATE TGF BETA, BUT IF A

5198
03:06:40,648 --> 03:06:41,749
MICROBIOTA AND ASSOCIATED

5199
03:06:41,749 --> 03:06:43,718
CONVERSION TO SECONDARY BILE

5200
03:06:43,718 --> 03:06:45,453
ACID WAS AN OPTION, YOU GET AN

5201
03:06:45,453 --> 03:06:47,655
INCREASE IN INTERFERON BETA.

5202
03:06:47,655 --> 03:06:51,359
AND OVERALL THAT SUGGESTS TO US

5203
03:06:51,359 --> 03:06:53,227
THAT THE CD4 T-CELLS THAT ARE

5204
03:06:53,227 --> 03:06:55,196
GOING TO GET INFECTED AND ALLOW

5205
03:06:55,196 --> 03:06:58,699
THE HIV TO PERSIST WILL RESPOND

5206
03:06:58,699 --> 03:07:01,736
DIFFERENTLY IF YOU HAVE

5207
03:07:01,736 --> 03:07:02,970
MICROBIOME ASSOCIATED MILIEU

5208
03:07:02,970 --> 03:07:04,806
THAT IS IN THE PRESENCE OF

5209
03:07:04,806 --> 03:07:07,008
PRIMARY BILE ACIDS VERSUS

5210
03:07:07,008 --> 03:07:07,775
SECONDARY BILE ACIDS.

5211
03:07:07,775 --> 03:07:09,544
ON THE ONE HAND, THE PRIMARY

5212
03:07:09,544 --> 03:07:11,078
BILE ACIDS WILL PROMOTE HIGH

5213
03:07:11,078 --> 03:07:14,115
LEVELS OF TGF BETA AND ALLOW FOR

5214
03:07:14,115 --> 03:07:16,083
RESERVOIR PERSISTENCE, WHEREAS

5215
03:07:16,083 --> 03:07:18,386
THE SECONDARY PROMOTE TYPE I

5216
03:07:18,386 --> 03:07:20,655
INTERFERONS WHICH PREVENT

5217
03:07:20,655 --> 03:07:21,989
RESERVOIR SEEDING AND PREVENT

5218
03:07:21,989 --> 03:07:22,323
INFECTION.

5219
03:07:22,323 --> 03:07:24,859
SO THOSE ARE A FEW HIGHLIGHTS,

5220
03:07:24,859 --> 03:07:28,863
BUT GLOBALLY, WE HAVE BEEN ABLE

5221
03:07:28,863 --> 03:07:32,266
TO ESTABLISH THAT ALL OF THESE

5222
03:07:32,266 --> 03:07:34,669
FEATURES HERE, PRIMARY BILE

5223
03:07:34,669 --> 03:07:37,638
ACID, SHORT CHAIN FATTY ACID,

5224
03:07:37,638 --> 03:07:39,474
INCREASE IN T REGS AND

5225
03:07:39,474 --> 03:07:41,342
DYSFUNCTIONAL TCMs, SO TCMs

5226
03:07:41,342 --> 03:07:45,279
ARE DRIVERS OF HIGH RESERVOIR IN

5227
03:07:45,279 --> 03:07:47,248
OUR ANTIRETROVIRAL THERAPY

5228
03:07:47,248 --> 03:07:49,750
TREATED COHORTS, BUT IF YOU HAVE

5229
03:07:49,750 --> 03:07:52,820
INDIVIDUAL THS THAT ARE ABLE TO

5230
03:07:52,820 --> 03:07:55,890
MAINTAIN A MILIEU WITH INCREASED

5231
03:07:55,890 --> 03:07:57,758
INTERFERON -- TYPE 1 INTERFERON

5232
03:07:57,758 --> 03:08:01,796
OR IL-4, YOU SEE A REDUCTION IN

5233
03:08:01,796 --> 03:08:03,531
THE RESERVOIR, YOU OBSERVE THOSE

5234
03:08:03,531 --> 03:08:04,298
INDIVIDUALS HAVE LOWER

5235
03:08:04,298 --> 03:08:05,199
RESERVOIR.

5236
03:08:05,199 --> 03:08:06,934
AND WITH THAT, I'M GOING TO TURN

5237
03:08:06,934 --> 03:08:09,871
IT OVER TO RAFICK BUT BEFORE I

5238
03:08:09,871 --> 03:08:11,072
TO THAT, I JUST WANT TO

5239
03:08:11,072 --> 03:08:12,740
ACKNOWLEDGE THAT THIS WORK IS

5240
03:08:12,740 --> 03:08:14,809
BEING DONE ACROSS MULTIPLE

5241
03:08:14,809 --> 03:08:16,777
CONTINENTS.

5242
03:08:16,777 --> 03:08:21,482
WE HAVE THE TEAM IN GENDT AND

5243
03:08:21,482 --> 03:08:22,783
JAVIER'S TEAM IN BARCELONA AND

5244
03:08:22,783 --> 03:08:25,219
HAVE BEEN WORKING WITH OUR GROUP

5245
03:08:25,219 --> 03:08:28,856
AT EMORY LED BY RAFICK AND THE

5246
03:08:28,856 --> 03:08:31,859
PRIMATE CENTER AND VINCE

5247
03:08:31,859 --> 03:08:33,194
MARCONI'S GROUP AT UNIVERSITY

5248
03:08:33,194 --> 03:08:34,462
HOSPITALS AND VETERANS AFFAIRS

5249
03:08:34,462 --> 03:08:37,231
HOSPITAL AT EMORY, AND THEN

5250
03:08:37,231 --> 03:08:40,735
MERCK AND LAZAN ARE ALSO

5251
03:08:40,735 --> 03:08:41,002
INVOLVED.

5252
03:08:41,002 --> 03:08:41,402
THANK YOU.

5253
03:08:41,402 --> 03:08:46,340
[APPLAUSE]

5254
03:08:46,340 --> 03:08:49,911
>> GOOD AFTERNOON,
EVERYONE.

5255
03:08:49,911 --> 03:08:51,546
BILE ACIDS ARE KNOWN TO PUT

5256
03:08:51,546 --> 03:08:52,847
PEOPLE TO SLEEP SO I WON'T TALK

5257
03:08:52,847 --> 03:08:54,715
TOO MUCH ABOUT BILE ACIDS, BUT

5258
03:08:54,715 --> 03:08:59,120
SO I THINK IT'S A GREAT THING TO

5259
03:08:59,120 --> 03:09:01,489
BE HERE AND PRESENT TO YOU WHAT

5260
03:09:01,489 --> 03:09:04,892
WE'VE BEEN DOING IN RF 2, LED BY

5261
03:09:04,892 --> 03:09:06,861
JAVIER AND VINCE MARCONI.

5262
03:09:06,861 --> 03:09:08,896
I'M TALKING ON BEHALF OF THEM

5263
03:09:08,896 --> 03:09:10,164
AND ON BEHALF OF THE WHOLE

5264
03:09:10,164 --> 03:09:13,668
GROUP.

5265
03:09:13,668 --> 03:09:14,969
SOMETHING WE'VE BEEN

5266
03:09:14,969 --> 03:09:15,736
BRAINSTORMING A LOT ABOUT FOR

5267
03:09:15,736 --> 03:09:17,038
MANY, MANY YEARS AND REALLY WE

5268
03:09:17,038 --> 03:09:18,139
WANT TO BE A LITTLE BIT

5269
03:09:18,139 --> 03:09:19,340
DIFFERENT OR MORE DIFFERENT THAN

5270
03:09:19,340 --> 03:09:21,075
WHAT EVERYBODY ELSE IS DOING,

5271
03:09:21,075 --> 03:09:23,711
AND REALLY TRY TO FOCUS ON WHAT

5272
03:09:23,711 --> 03:09:25,813
ARE THE MECHANISMS, THE MOST --

5273
03:09:25,813 --> 03:09:27,982
THAT CAN REGULATE COMMUNITY

5274
03:09:27,982 --> 03:09:31,218
CONSTITUTION AND ALSO -- SO IF

5275
03:09:31,218 --> 03:09:32,987
YOU LOOK AT THE WIDE SCOPE OF

5276
03:09:32,987 --> 03:09:35,189
BIOLOGY AND IMMUNOTHERAPY YOU

5277
03:09:35,189 --> 03:09:38,926
UNDERSTAND IN CANCER, THE

5278
03:09:38,926 --> 03:09:40,127
MICROBES AND METABOLITES ARE THE

5279
03:09:40,127 --> 03:09:42,296
ONES THAT REALLY REGULATE THE

5280
03:09:42,296 --> 03:09:48,869
RESPONSE IN ANTIPD-1, WHETHER

5281
03:09:48,869 --> 03:09:50,171
IBD OR CANCER, AGAIN THE FOCUS

5282
03:09:50,171 --> 03:09:52,173
ON HOW YOU CAN MODULATE THE

5283
03:09:52,173 --> 03:09:55,443
MICROBIOME, THE METABALOME,

5284
03:09:55,443 --> 03:09:56,744
OTHER IMMUNOTHERAPIES, THIS IS

5285
03:09:56,744 --> 03:09:57,511
WHERE THE CRUX IS.

5286
03:09:57,511 --> 03:10:01,015
AND IN FACT, YOU GO BACK --

5287
03:10:01,015 --> 03:10:02,650
PUBLISHED FOR MANY YEARS AGAIN

5288
03:10:02,650 --> 03:10:05,152
YOU UNDERSTAND THAT EVEN

5289
03:10:05,152 --> 03:10:07,355
PREVACCINATION, OR PREANY IMMUNE

5290
03:10:07,355 --> 03:10:08,889
INTERVENTION, THE STATE OF THE

5291
03:10:08,889 --> 03:10:10,958
HOST PREINTERVENTION, IS

5292
03:10:10,958 --> 03:10:12,059
CRITICAL TO WHETHER YOU'RE GOING

5293
03:10:12,059 --> 03:10:14,028
TO RESPOND TO IMMUNOTHERAPY.

5294
03:10:14,028 --> 03:10:15,429
THAT STATE IS REALLY DICTATED

5295
03:10:15,429 --> 03:10:18,399
AGAIN BY THE MICROBES AND THE

5296
03:10:18,399 --> 03:10:18,699
METABOLITES.

5297
03:10:18,699 --> 03:10:22,336
SO WITH THAT IN MIND, I THINK WE

5298
03:10:22,336 --> 03:10:26,040
WENT WITH -- WE HAD VERY MUCH

5299
03:10:26,040 --> 03:10:30,411
FORTUNE OF -- THAT ASHISH LISTED

5300
03:10:30,411 --> 03:10:34,281
BUT ON TOP WE ALSO HAD COHORTS

5301
03:10:34,281 --> 03:10:36,550
OF INDIVIDUALS THAT HAD

5302
03:10:36,550 --> 03:10:37,151
UNDERGONE SEVERAL DIFFERENT

5303
03:10:37,151 --> 03:10:38,853
TYPES OF IMMUNOTHERAPIES AND OUR

5304
03:10:38,853 --> 03:10:40,254
GOAL WAS TO TRY TO FIGURE OUT

5305
03:10:40,254 --> 03:10:41,422
WHETHER THERE WAS A COMMON

5306
03:10:41,422 --> 03:10:43,424
MECHANISM THAT ARE GOING TO

5307
03:10:43,424 --> 03:10:46,293
PREDICT WHO WAS GOING TO RESP 

5308
03:10:46,293 --> 03:10:47,495
RESPOND, AND RESPONSES THEY'RE

5309
03:10:47,495 --> 03:10:52,400
LOOKING FOR IS WHETHER IT WAS

5310
03:10:52,400 --> 03:10:57,004
GOING TO LEAD TO DECAY OR ABLE

5311
03:10:57,004 --> 03:10:58,205
TO CONTROL -- THAT'S ESSENTIALLY

5312
03:10:58,205 --> 03:10:59,407
WHAT I'M GOING TO TALK TO YOU

5313
03:10:59,407 --> 03:11:04,912
ABOUT IN THE NEXT FEW MINUTES.

5314
03:11:04,912 --> 03:11:12,019
THE KEY QUESTIONS -- PERSISTENT

5315
03:11:12,019 --> 03:11:15,022
OR IN FACT THE REVERSE, IMPACT

5316
03:11:15,022 --> 03:11:18,693
ON ROOT HE SPONS TO

5317
03:11:18,693 --> 03:11:20,961
INTERVENTION, HOLISTIC APPROACH

5318
03:11:20,961 --> 03:11:24,265
IN ORDER TO DEFINE UNBIASED

5319
03:11:24,265 --> 03:11:25,232
WAYS -- NOVEL TARGETS THAT GIVES

5320
03:11:25,232 --> 03:11:26,901
US CLUES ON WHAT NOVEL TARGETS

5321
03:11:26,901 --> 03:11:34,975
CAN PURSUE -- I THINK IN TERMS

5322
03:11:34,975 --> 03:11:37,845
OF WHAT WE HAVE ACCOMPLISHED, I

5323
03:11:37,845 --> 03:11:39,914
THINK REALLY WHAT WE ARE REALLY

5324
03:11:39,914 --> 03:11:42,516
FOCUSED ON IS REALLY DEFINED

5325
03:11:42,516 --> 03:11:43,517
PATHWAY, THAT EXAMPLE I'M GOING

5326
03:11:43,517 --> 03:11:45,619
TO GIVE YOU IS THAT WE HAVE

5327
03:11:45,619 --> 03:11:47,054
GENERIC SIGNATURES THAT CAN

5328
03:11:47,054 --> 03:11:48,656
PREDICT A RESPONSE TO AT LEAST

5329
03:11:48,656 --> 03:11:50,391
THREE DIFFERENT TYPES OF

5330
03:11:50,391 --> 03:11:51,158
IMMUNOTHERAPIES.

5331
03:11:51,158 --> 03:11:52,493
THAT'S WHAT I REALLY WOULD LIKE

5332
03:11:52,493 --> 03:11:56,530
TO BUILD UPON TOGETHER, IN ORDER

5333
03:11:56,530 --> 03:12:01,569
TO BE ABLE TO EVEN ENHANCE -- I

5334
03:12:01,569 --> 03:12:03,537
WANT TO GO INTO HUMAN AS MUCH AS

5335
03:12:03,537 --> 03:12:04,405
POSSIBLE, I KNOW IT'S NOT PART

5336
03:12:04,405 --> 03:12:07,041
OF THIS, BUT MY GOAL IS REALLY

5337
03:12:07,041 --> 03:12:13,147
TO GO IN HUMAN.

5338
03:12:13,147 --> 03:12:16,751
THE TITLE OF OUR CONSORTIUM IS

5339
03:12:16,751 --> 03:12:18,285
IMMUNE CONSTITUTION,

5340
03:12:18,285 --> 03:12:20,488
IMMUNOTHERAPIES AND THAT'S

5341
03:12:20,488 --> 03:12:22,556
WHAT -- ABOUT AND IT'S IMPORTANT

5342
03:12:22,556 --> 03:12:24,625
BECAUSE YES THERE ARE LRAs,

5343
03:12:24,625 --> 03:12:26,594
THEY HAVE NOT SHOWN MUCH

5344
03:12:26,594 --> 03:12:26,827
SUCCESS.

5345
03:12:26,827 --> 03:12:29,230
I THINK I'LL SHOW YOU DATA THAT

5346
03:12:29,230 --> 03:12:30,564
AT LEAST SOME IMMUNOTHERAPIES

5347
03:12:30,564 --> 03:12:36,103
HAVE HAD SOME SUCCESS IN CURBING

5348
03:12:36,103 --> 03:12:37,338
THE RESERVOIR AND CONTROLLING

5349
03:12:37,338 --> 03:12:39,840
VIRAL LOAD.

5350
03:12:39,840 --> 03:12:43,344
SO TODAY I'M GOING TO SHOW YOU

5351
03:12:43,344 --> 03:12:48,482
THE STUDY THAT SUSAN AND MIRKO

5352
03:12:48,482 --> 03:12:50,017
HAVE SHOWN, GO BACK TO BILE

5353
03:12:50,017 --> 03:12:53,387
ACIDS AND SHOW HOW BILE ACIDS

5354
03:12:53,387 --> 03:12:55,489
MECHANISM IS ONE THAT TRIGGERS

5355
03:12:55,489 --> 03:12:57,958
THE RESPONSE TO DIFFERENT -- SO

5356
03:12:57,958 --> 03:13:01,162
YOU'VE SEEN THAT SLIDE EARLIER.

5357
03:13:01,162 --> 03:13:04,799
THIS IS I THINK A GROUNDBREAKING

5358
03:13:04,799 --> 03:13:06,967
STUDY THAT SUSAN LED TOGETHER

5359
03:13:06,967 --> 03:13:10,237
WITH THE GROUP WHERE WE TREATED

5360
03:13:10,237 --> 03:13:13,407
MONKEYS WITH ANTIPD-1 AND IL-10,

5361
03:13:13,407 --> 03:13:17,678
IT COMES FROM VERY HARD -- SO A

5362
03:13:17,678 --> 03:13:20,080
CONCEPT INITIALLY DONE BY

5363
03:13:20,080 --> 03:13:24,618
MICHAEL -- WHERE THE -- REGULATE

5364
03:13:24,618 --> 03:13:26,086
MANY DIFFERENT INNATE TYPE

5365
03:13:26,086 --> 03:13:28,622
MECHANISM THAT ARE ABLE TO

5366
03:13:28,622 --> 03:13:30,157
INTERACT, HELP PRIME THE IMMUNE

5367
03:13:30,157 --> 03:13:33,427
RESPONSE AND GET TO CONTROL

5368
03:13:33,427 --> 03:13:40,334
OF -- UP TO -- WEEKS AFTER

5369
03:13:40,334 --> 03:13:41,535
STOPPING ART THEY WERE ABLE TO

5370
03:13:41,535 --> 03:13:44,138
CONTROL VIRAL LOAD.

5371
03:13:44,138 --> 03:13:48,409
 -- LEVELS AS COMPARED TO THE

5372
03:13:48,409 --> 03:13:49,276
ANTIIL-10 -- SO AGAIN IN THE

5373
03:13:49,276 --> 03:13:51,145
TRUE SPEESHT OF WHAT WE DO IN MY

5374
03:13:51,145 --> 03:13:55,950
GROUP, WE LOOKED AT WHAT ARE THE

5375
03:13:55,950 --> 03:13:58,686
PATHWAYS THAT -- PREDICT THE

5376
03:13:58,686 --> 03:14:00,654
CONTROL OF -- EVERYTHING WE DO

5377
03:14:00,654 --> 03:14:04,592
NOW IS PRE-ATI.

5378
03:14:04,592 --> 03:14:07,094
AMONG THE FIRST ONE, TOP ONE WAS

5379
03:14:07,094 --> 03:14:10,831
BILE ACIDS AND INTERFERON.

5380
03:14:10,831 --> 03:14:14,435
SO INTERFERON, THAT SHOWED THAT

5381
03:14:14,435 --> 03:14:17,705
WHEN YOU INFUSE INTERFERON, YOU

5382
03:14:17,705 --> 03:14:23,978
CAN CURB THE INFECTION BUT

5383
03:14:23,978 --> 03:14:25,713
ALSO -- REBOUND BUT WHY BILE

5384
03:14:25,713 --> 03:14:28,115
ACIDS?

5385
03:14:28,115 --> 03:14:29,316
BECAUSE BRIEFLY MENTIONED TO

5386
03:14:29,316 --> 03:14:31,385
YOU, BILE ACIDS ARE MODULATED BY

5387
03:14:31,385 --> 03:14:35,422
THE MICROBIOME SO AGAIN

5388
03:14:35,422 --> 03:14:37,057
INTERPLAY, THEY'RE THE ONES THAT

5389
03:14:37,057 --> 03:14:41,996
ARE ABLE TO TRIGGER --

5390
03:14:41,996 --> 03:14:42,963
INTERFERON.

5391
03:14:42,963 --> 03:14:45,699
IF IT'S IN A STATE OF -- BEFORE

5392
03:14:45,699 --> 03:14:47,034
VIRAL LOAD COMES BACK, WHEN YOU

5393
03:14:47,034 --> 03:14:49,436
STOP TREATMENT OF COURSE YOU

5394
03:14:49,436 --> 03:14:52,273
HAVE AN IMMUNE SYSTEM THAT'S

5395
03:14:52,273 --> 03:14:55,009
POISED AND ENHANCE IMMUNE

5396
03:14:55,009 --> 03:14:56,977
RESPONSE BECAUSE INTERFERON IS A

5397
03:14:56,977 --> 03:14:58,612
MAJOR ADJUVANT BUT ALSO IT

5398
03:14:58,612 --> 03:14:59,713
PROTECTS OLDER CELLS FROM

5399
03:14:59,713 --> 03:15:03,217
GETTING REINFECTED, SO I THINK

5400
03:15:03,217 --> 03:15:06,120
TO MAKE THE LAW OF LOGIC, THE

5401
03:15:06,120 --> 03:15:07,821
TWO ARE VERY MUCH INTERRELATED,

5402
03:15:07,821 --> 03:15:10,658
TO LEAD TO -- VIRAL REBOUND POST

5403
03:15:10,658 --> 03:15:10,858
ATI.

5404
03:15:10,858 --> 03:15:15,229
IN FACT WE IDENTIFY SEVERAL

5405
03:15:15,229 --> 03:15:17,431
INDIVIDUAL BILE ACIDS THAT ARE

5406
03:15:17,431 --> 03:15:19,300
NEGATIVELY CORRELATED TO

5407
03:15:19,300 --> 03:15:21,168
VIREMIA, PREATI AGAIN, SO THE

5408
03:15:21,168 --> 03:15:24,004
MORE THOSE BILE ACIDS, THELESS

5409
03:15:24,004 --> 03:15:26,073
IMMUNE, THE LESS VIRAL REBOUND

5410
03:15:26,073 --> 03:15:28,475
YOU'RE GOING TO GET.

5411
03:15:28,475 --> 03:15:30,778
SO THAT CAN BE A WHOLE TALK BUT

5412
03:15:30,778 --> 03:15:32,179
I JUST WANT TO GIVE THE GIST OF

5413
03:15:32,179 --> 03:15:34,481
IT WHICH AGAIN RELATES TO WORK

5414
03:15:34,481 --> 03:15:36,250
THAT WAS PUBLISHED ABOUT A YEAR

5415
03:15:36,250 --> 03:15:38,319
AGO WHERE IN FACT THAT THOSE

5416
03:15:38,319 --> 03:15:41,622
BILE ACIDS DO REALLY TO PRIME,

5417
03:15:41,622 --> 03:15:44,458
TO PUT THE INTERFERON LOCUS IN

5418
03:15:44,458 --> 03:15:44,992
A -- STATE.

5419
03:15:44,992 --> 03:15:49,363
SO WE DID SINGLE CELL SEQ AND

5420
03:15:49,363 --> 03:15:51,665
I'M SHOWING YOU HERE THE POISE

5421
03:15:51,665 --> 03:15:53,100
STATE OF FOUR GENES WHICH ARE IN

5422
03:15:53,100 --> 03:15:54,835
FACT THE GENES THAT REGULATE

5423
03:15:54,835 --> 03:15:58,539
INTERFERON RESPONSE, THE IRFs,

5424
03:15:58,539 --> 03:16:00,207
IRF7, MASTER REGULATOR OF IMMUNE

5425
03:16:00,207 --> 03:16:04,144
RESPONSES AND YOU SEE THAT THOSE

5426
03:16:04,144 --> 03:16:05,546
ARE ALL IN A POISE STATE AND

5427
03:16:05,546 --> 03:16:07,948
WHAT YOU SEE IN CIRCLES ARE THE

5428
03:16:07,948 --> 03:16:11,485
CD4 T-CELLS, SO YO THEY'RE ALREY

5429
03:16:11,485 --> 03:16:13,387
PROTECTED FROM GETTING INFECTED

5430
03:16:13,387 --> 03:16:15,556
BECAUSE ALL THE INTERFERON --

5431
03:16:15,556 --> 03:16:17,291
ALREADY AND THE ANTIVIRAL

5432
03:16:17,291 --> 03:16:18,826
INTERFERONS ARE BEING

5433
03:16:18,826 --> 03:16:19,159
UPREGULATED.

5434
03:16:19,159 --> 03:16:22,196
WHAT I DON'T SHOW YOU ALSO --

5435
03:16:22,196 --> 03:16:28,569
INNATE HUMAN CELLS -- TO FOLLOW

5436
03:16:28,569 --> 03:16:33,807
UP ON, WE SHOWED IN MACAQUES

5437
03:16:33,807 --> 03:16:37,077
WE'RE NOT ABLE TO CONTROL

5438
03:16:37,077 --> 03:16:41,448
VIREMIA, SHOWED YOU THE MAJOR

5439
03:16:41,448 --> 03:16:43,117
REGULATOR -- HUMAN DYSFUNCTION,

5440
03:16:43,117 --> 03:16:45,185
THAT IN MONKEYS WERE NOT ABLE TO

5441
03:16:45,185 --> 03:16:48,122
PROTECT THAT LOCUS IS OPEN.

5442
03:16:48,122 --> 03:16:50,958
SO IN MONKEYS WHICH ARE

5443
03:16:50,958 --> 03:16:52,292
PROTECTED IT'S OPEN, IN MONKEYS

5444
03:16:52,292 --> 03:16:54,695
THAT ARE NOT PROTECTED -- SO IT

5445
03:16:54,695 --> 03:16:55,796
GIVES YOU A VERY STRONG

5446
03:16:55,796 --> 03:16:58,198
MOLECULAR BASIS FOR THE EFFECT

5447
03:16:58,198 --> 03:16:59,266
THAT YOU ARE SEEING.

5448
03:16:59,266 --> 03:17:01,702
SO AT LEAST IN SUMMARY, WHAT THE

5449
03:17:01,702 --> 03:17:04,304
STUDY ALREADY SHOWS US IS THAT

5450
03:17:04,304 --> 03:17:06,073
IN FACT YOU HAVE A VERY STRONG

5451
03:17:06,073 --> 03:17:09,109
ROBUST INNATE RESPONSE EARLY ON

5452
03:17:09,109 --> 03:17:11,211
WHICH IS DOWNSTREAM OF BILE

5453
03:17:11,211 --> 03:17:13,480
ACIDS AND THOSE INTEGRATE

5454
03:17:13,480 --> 03:17:15,049
TOGETHER, ABLE TO PRIME THE

5455
03:17:15,049 --> 03:17:18,185
IMMUNE RESPONSE BUT ALSO TO

5456
03:17:18,185 --> 03:17:22,156
PROTECT -- SO THE NEXT STEP,

5457
03:17:22,156 --> 03:17:26,427
WHAT WE DID IS TO EXTEND OUR

5458
03:17:26,427 --> 03:17:27,561
PLANNINGS TO THREE ADVANCE

5459
03:17:27,561 --> 03:17:27,795
STUDIES.

5460
03:17:27,795 --> 03:17:33,067
ONE WHERE WE INFUSED INTO YOUR

5461
03:17:33,067 --> 03:17:34,601
HOST, IN ONE SUBJECT THAT WE

5462
03:17:34,601 --> 03:17:41,075
WERE ABLE TO SHOW OVER THREE

5463
03:17:41,075 --> 03:17:42,609
YEARS BUT ALSO IN SUBJECTS WE

5464
03:17:42,609 --> 03:17:45,446
WERE ABLE TO STOP ATI UPON

5465
03:17:45,446 --> 03:17:48,048
INFUSION, THE SUBJECTS WERE ABLE

5466
03:17:48,048 --> 03:17:49,383
TO CONTROL VIRAL LOAD FOR UP TO

5467
03:17:49,383 --> 03:17:50,584
SEVEN YEARS, ONE OF THEM AT

5468
03:17:50,584 --> 03:17:51,118
LEAST.

5469
03:17:51,118 --> 03:17:55,856
TWO OTHER STUDIES, ANTIPD-1 IN

5470
03:17:55,856 --> 03:17:57,224
PERSONS LIVING WITH HIV, ALSO

5471
03:17:57,224 --> 03:17:58,358
CANCER WE WERE ABLE TO SHOW

5472
03:17:58,358 --> 03:18:02,062
AGAIN THE STUDIES WITH SHARON

5473
03:18:02,062 --> 03:18:03,831
LEWIN AND STEVE ALSO HAVE --

5474
03:18:03,831 --> 03:18:12,473
WERE PART OF, THAT UPON THE

5475
03:18:12,473 --> 03:18:13,340
INFUSION, WE HAD CLEAR

5476
03:18:13,340 --> 03:18:14,741
SIGNATURE.

5477
03:18:14,741 --> 03:18:16,844
ONE DAY -- THAT PREDICT THE

5478
03:18:16,844 --> 03:18:18,045
OUTCOME TWO YEARS LATER, AND

5479
03:18:18,045 --> 03:18:20,314
AGAIN THE STUDY -- WHICH I JUST

5480
03:18:20,314 --> 03:18:21,548
SHOWED YOU, NOW WHEN YOU MERGE

5481
03:18:21,548 --> 03:18:23,217
ALL THESE DATA AND YOU TRY TO

5482
03:18:23,217 --> 03:18:25,419
FIGURE OUT WHETHER SIGNATURE

5483
03:18:25,419 --> 03:18:28,322
THAT IS COMING TO ALL THOSE

5484
03:18:28,322 --> 03:18:29,723
PRE-ATI OR IMMEDIATELY POST

5485
03:18:29,723 --> 03:18:31,158
INFUSION, AGAIN WHAT REALLY PANS

5486
03:18:31,158 --> 03:18:33,994
OUT IS INTERFERON -- THAT ARE

5487
03:18:33,994 --> 03:18:36,630
BEING CIRCLED OR SQUARED, ALL

5488
03:18:36,630 --> 03:18:39,566
THESE ARE -- SO THE MOTHER THAT

5489
03:18:39,566 --> 03:18:43,837
YOU HAVE IS WHATEVER IMMUNE

5490
03:18:43,837 --> 03:18:46,573
INTERVENTION, IS IT -- WHERE THE

5491
03:18:46,573 --> 03:18:47,541
INTERFERON LOCUS IS OPEN, YOU'RE

5492
03:18:47,541 --> 03:18:50,844
GOING TO HAVE PRIME CD4 T-CELLS

5493
03:18:50,844 --> 03:18:53,046
TO IN FACT PROVIDE HELP TO

5494
03:18:53,046 --> 03:18:54,114
CD8 T-CELLS, SO IF THERE'S NO

5495
03:18:54,114 --> 03:18:56,950
HELP, YOU WON'T GET PERSISTENT

5496
03:18:56,950 --> 03:18:58,285
CD8s AND YOU WILL GET

5497
03:18:58,285 --> 03:18:59,820
EXHAUSTION, BUT AT THE SAME

5498
03:18:59,820 --> 03:19:01,221
TIME, YOU'RE PROTECTING T-CELLS

5499
03:19:01,221 --> 03:19:02,656
OR OTHER CELLS FROM GETTING

5500
03:19:02,656 --> 03:19:02,923
INFECTED.

5501
03:19:02,923 --> 03:19:04,625
SO THIS IS REALLY A CONCEPT THAT

5502
03:19:04,625 --> 03:19:10,731
NOW WE WANT TO GO INTO NO NON-HN

5503
03:19:10,731 --> 03:19:12,866
PRIMATE, BUT ALSO IN HUMAN,

5504
03:19:12,866 --> 03:19:13,901
CLINICAL TRIALS, I'LL BE ABLE TO

5505
03:19:13,901 --> 03:19:15,435
PRESENT TO YOU IN THE NEXT

5506
03:19:15,435 --> 03:19:19,473
ITERATION OF THIS PROGRAM.

5507
03:19:19,473 --> 03:19:21,241
SO OF COURSE I JUST COLLECT THE

5508
03:19:21,241 --> 03:19:24,745
DATA AND THINK ABOUT THEM, AND I

5509
03:19:24,745 --> 03:19:25,879
HAVE AN AMAZING GROUP OF PEOPLE

5510
03:19:25,879 --> 03:19:28,582
THAT WORK WITH ME.

5511
03:19:28,582 --> 03:19:30,083
REALLY LEADERS IN THE FIELD.

5512
03:19:30,083 --> 03:19:31,852
AND WILL TAKE MY LEGACY FORWARD

5513
03:19:31,852 --> 03:19:34,354
AND THEN, OF COURSE, ALL THE

5514
03:19:34,354 --> 03:19:37,758
COHORT, MY COLLEAGUES, JAVIER,

5515
03:19:37,758 --> 03:19:41,695
NINOS AND THEIR COLLEAGUES, AND

5516
03:19:41,695 --> 03:19:41,929
SUMITA.

5517
03:19:41,929 --> 03:19:42,229
THANK YOU.

5518
03:19:42,229 --> 03:19:47,167
[APPLAUSE]

5519
03:19:47,167 --> 03:19:48,702
>> OKAY, SO I'M GOING TO
GIVE

5520
03:19:48,702 --> 03:19:52,072
YOU A HIGH LEVEL TOUR THROUGH RF

5521
03:19:52,072 --> 03:19:53,707
3, COMBINING VARIOUS STRATEGIES

5522
03:19:53,707 --> 03:19:56,109
THROUGH RESERVOIR ELIMINATION.

5523
03:19:56,109 --> 03:19:57,878
WE HAVE REACTIVATION OF LATENT

5524
03:19:57,878 --> 03:20:00,514
GENOMES, WE HAVE A CRISPR-BASED

5525
03:20:00,514 --> 03:20:01,481
TECHNOLOGY TO DISRUPT YEE NOMES

5526
03:20:01,481 --> 03:20:07,821
AND WE -- BASEDON ADCC AND NSM .

5527
03:20:07,821 --> 03:20:09,456
AND HERE IS SHOWN THE DIVERSE

5528
03:20:09,456 --> 03:20:11,992
TEAM OF PEOPLE WHO ARE INVOLVED

5529
03:20:11,992 --> 03:20:13,093
IN THIS.

5530
03:20:13,093 --> 03:20:15,495
THIS IS LED BY MYSELF AND SUMIT.

5531
03:20:15,495 --> 03:20:16,930
SO A SUMMARY, CAN WE COMBINE

5532
03:20:16,930 --> 03:20:18,098
THESE VARIOUS TREATMENTS TO

5533
03:20:18,098 --> 03:20:19,533
REDUCE THE RESERVOIR?

5534
03:20:19,533 --> 03:20:22,936
WHAT WE'VE ACCOMPLISHED SO FAR,

5535
03:20:22,936 --> 03:20:24,238
WE'VE GOT NEW VERSIONS OF

5536
03:20:24,238 --> 03:20:26,873
LATENCY REVERSING DRUGS TO

5537
03:20:26,873 --> 03:20:29,076
ELIMINATE LATENT HIV, WE'VE GOT

5538
03:20:29,076 --> 03:20:31,044
PROGRESS, USING NATURAL KILLER

5539
03:20:31,044 --> 03:20:32,879
CELLS, B CELLS AND ANTIBODIES.

5540
03:20:32,879 --> 03:20:34,848
AND WE DEVELOPED GENE EDITING

5541
03:20:34,848 --> 03:20:36,717
TOOLS TO DIRECTLY ATTACK LATENT

5542
03:20:36,717 --> 03:20:37,284
HIV GENOMES.

5543
03:20:37,284 --> 03:20:38,585
OF COURSE THIS IS IMPORTANT AND

5544
03:20:38,585 --> 03:20:40,754
RELATES TO OUR AGENDA BECAUSE WE

5545
03:20:40,754 --> 03:20:41,855
BELIEVE WE'RE GOING TO NEED TO

5546
03:20:41,855 --> 03:20:43,624
REDUCE THE RESERVOIR TO ALLOW

5547
03:20:43,624 --> 03:20:46,026
THE IMMUNE THERAPIES THAT YOU'VE

5548
03:20:46,026 --> 03:20:48,428
HEARD ABOUT FOR THEM TO HAVE A

5549
03:20:48,428 --> 03:20:50,397
CHANCE TO WORK.

5550
03:20:50,397 --> 03:20:52,599
SO FIRST OF ALL THE WORK THAT'S

5551
03:20:52,599 --> 03:20:54,334
BEING DONE ON RESERVOIR

5552
03:20:54,334 --> 03:20:56,737
REACTIVATION MOSTLY DRIVEN BY

5553
03:20:56,737 --> 03:20:57,938
LARS AND SUMIT.

5554
03:20:57,938 --> 03:21:01,875
SO THE IDEA HERE IS THAT WE

5555
03:21:01,875 --> 03:21:03,510
RECOGNIZE LRAs ARE LIKELY TO

5556
03:21:03,510 --> 03:21:06,346
NEED REPEAT DOSING SO

5557
03:21:06,346 --> 03:21:08,215
OPTIMIZATION OF THEIR CHEMISTRY,

5558
03:21:08,215 --> 03:21:09,750
REDUCED TOXICITY AND DOSING

5559
03:21:09,750 --> 03:21:10,517
REGIMENS IS GOING TO BE

5560
03:21:10,517 --> 03:21:11,952
IMPORTANT.

5561
03:21:11,952 --> 03:21:13,353
SO THE TEAM HAVE DEVELOPED A

5562
03:21:13,353 --> 03:21:16,757
WHOLE SERIES OF NEW NOVEL SMACK

5563
03:21:16,757 --> 03:21:18,292
MIMETICS WHICH THE

5564
03:21:18,292 --> 03:21:19,293
CHARACTERISTICS ARE SHOWN IN THE

5565
03:21:19,293 --> 03:21:20,060
GRAPH ON THE LEFT.

5566
03:21:20,060 --> 03:21:22,796
THEY'RE ALL ABLE TO REACTIVATE

5567
03:21:22,796 --> 03:21:26,099
LATENT HIV IN JLAT CELLS.

5568
03:21:26,099 --> 03:21:27,401
IN ADDITION THEY HAVE A RANGE OF

5569
03:21:27,401 --> 03:21:31,438
DIFFERENT PK AND PD PROPERTIES,

5570
03:21:31,438 --> 03:21:33,206
SO ON THE RIGHT-HAND SIDE YOU'LL

5571
03:21:33,206 --> 03:21:37,577
SEE TWO DIFFERENT DRUGS,

5572
03:21:37,577 --> 03:21:41,715
CIAPAVIR AND SBP-6513 AND THEY

5573
03:21:41,715 --> 03:21:42,683
SHOW DIFFERENT CHARACTERISTICS

5574
03:21:42,683 --> 03:21:43,450
IN TIME OF ACTION.

5575
03:21:43,450 --> 03:21:44,217
AT THE SAME TIME WE'RE

5576
03:21:44,217 --> 03:21:45,319
INTERESTED IN IDENTIFYING

5577
03:21:45,319 --> 03:21:45,986
COMBINATIONINGS OF OTHER DRUGS

5578
03:21:45,986 --> 03:21:47,954
WE CAN COMBINE WITH THESE SMACK

5579
03:21:47,954 --> 03:21:48,555
MIMETICS.

5580
03:21:48,555 --> 03:21:54,261
SO HERE I'M SHOWING YOU A STUDY

5581
03:21:54,261 --> 03:22:01,368
WHERE CIAPAVIR IS BEING COMBINED

5582
03:22:01,368 --> 03:22:03,236
WITH TWO DIFFERENT SPEC

5583
03:22:03,236 --> 03:22:03,670
INHIBITORS.

5584
03:22:03,670 --> 03:22:05,439
THIS GIVES YOU DRUGS THAT ARE

5585
03:22:05,439 --> 03:22:06,640
FAR LESS TOXIC.

5586
03:22:06,640 --> 03:22:08,809
YOU'LL SEE ALL OF THEM SYNERGIZE

5587
03:22:08,809 --> 03:22:10,110
NICELY WITH CIAPAVIR.

5588
03:22:10,110 --> 03:22:13,280
AND THEN IN ADDITION, WE'RE ALSO

5589
03:22:13,280 --> 03:22:15,148
LOOKING FOR COMPLETELY NEW

5590
03:22:15,148 --> 03:22:16,016
LATENCY REACTIVATION DRUGS AND

5591
03:22:16,016 --> 03:22:18,118
WE'RE DOING THAT BY SCREENING

5592
03:22:18,118 --> 03:22:20,754
THE REFRAME LIBRARY WHICH IS

5593
03:22:20,754 --> 03:22:22,255
12,000 COMPOUNDS THAT ARE

5594
03:22:22,255 --> 03:22:24,991
FDA-APPROVED OR SORT OF NEAR

5595
03:22:24,991 --> 03:22:27,627
FDA-APPROVED, SOME FROM SORT OF

5596
03:22:27,627 --> 03:22:28,195
PRE-INDs.

5597
03:22:28,195 --> 03:22:28,829
IMPORTANTLY THEY'RE BEING

5598
03:22:28,829 --> 03:22:31,798
SCREENED NOT IN A CELL LINE

5599
03:22:31,798 --> 03:22:33,433
MODEL, BUT IN CD4 CELLS FROM

5600
03:22:33,433 --> 03:22:35,502
PEOPLE LIVING WITH HIV ON ART.

5601
03:22:35,502 --> 03:22:38,472
AND YOU'LL SEE ON THE GRAPH AT

5602
03:22:38,472 --> 03:22:40,107
THE BOTTOM THAT SHOWS SOME

5603
03:22:40,107 --> 03:22:41,108
INITIAL CHARACTERIZATION AND

5604
03:22:41,108 --> 03:22:41,942
SOME OF THE HITS THAT HAVE COME

5605
03:22:41,942 --> 03:22:42,642
OUT OF THIS.

5606
03:22:42,642 --> 03:22:46,012
SO WE'RE OPTIMISTIC THAT WE'LL

5607
03:22:46,012 --> 03:22:48,982
IDENTIFY BETTER, SAFER, POSSIBLY

5608
03:22:48,982 --> 03:22:50,717
COMBINATIONS OF LRAs THAT HAVE

5609
03:22:50,717 --> 03:22:51,918
BETTER PROPERTIES THAT FIT WITH

5610
03:22:51,918 --> 03:22:55,989
THE PROFILE FOR PEOPLE LIVING

5611
03:22:55,989 --> 03:22:59,025
WITH HIV.

5612
03:22:59,025 --> 03:23:00,327
MOVING ON TO SOME OF THE

5613
03:23:00,327 --> 03:23:02,095
APPROACHES WE'RE TAKING TO

5614
03:23:02,095 --> 03:23:03,163
ENHANCE IMMUNE CLEARANCE, I'M

5615
03:23:03,163 --> 03:23:05,165
GOING TO TELL YOU TWO STORIES,

5616
03:23:05,165 --> 03:23:06,767
HOW WE'RE RECRUITING MAs THIS,

5617
03:23:06,767 --> 03:23:10,971
IS WORK FROM JEFF MILLARD'S TEAM

5618
03:23:10,971 --> 03:23:14,574
AND MY WORK ON ENGINEERING B

5619
03:23:14,574 --> 03:23:15,776
CELLS.

5620
03:23:15,776 --> 03:23:21,448
SORE TRIKES RECOGNIZE BOTH --

5621
03:23:21,448 --> 03:23:23,984
THEY ALSO RECOGNIZE THE CD16

5622
03:23:23,984 --> 03:23:26,253
RECEPTOR ON NK CELLS.

5623
03:23:26,253 --> 03:23:28,121
THEREBY THEY DIRECT NK CELLS TO

5624
03:23:28,121 --> 03:23:30,857
AN INFECTED OR REACTIVATED CELL.

5625
03:23:30,857 --> 03:23:34,494
IN ADDITION, THEY ALSO HAVE

5626
03:23:34,494 --> 03:23:37,631
IL5-15 THAT SERVES TWO PURPOSES.

5627
03:23:37,631 --> 03:23:40,300
IT ACTIVATES THE NK CELLS AND

5628
03:23:40,300 --> 03:23:42,702
ALSO POTENTIALLY REACTIVATES

5629
03:23:42,702 --> 03:23:45,205
LATENT GENOMES.

5630
03:23:45,205 --> 03:23:46,173
JUST ONE PIECE OF DATA SHOWING

5631
03:23:46,173 --> 03:23:48,575
YOU THAT WE HAVE MADE TRIKES

5632
03:23:48,575 --> 03:23:53,079
THAT RECOGNIZE BOTH HIV AND SIV

5633
03:23:53,079 --> 03:23:54,948
AND CAN RECOGNIZE BOTH THE HUMAN

5634
03:23:54,948 --> 03:23:56,917
AND MACAQUE FORMS OF CD-16.

5635
03:23:56,917 --> 03:23:58,552
IN THE DATA I'M SHOWING YOU

5636
03:23:58,552 --> 03:24:00,187
HERE, THE LITTLE ARROWS POINT TO

5637
03:24:00,187 --> 03:24:01,621
THE ENHANCED KILLING THAT WE

5638
03:24:01,621 --> 03:24:03,356
ACHIEVE WHEN WE COMBINE NK CELLS

5639
03:24:03,356 --> 03:24:08,829
WITH TRIKES IN EITHER

5640
03:24:08,829 --> 03:24:11,798
REACTIVATED HIV OR SIV INFECTED

5641
03:24:11,798 --> 03:24:14,301
CELLS.

5642
03:24:14,301 --> 03:24:15,602
MY GROUP IS WORKING ON AND YOU

5643
03:24:15,602 --> 03:24:18,138
ALSO HAD A LITTLE BIT OF THIS

5644
03:24:18,138 --> 03:24:19,439
EARLIER FROM JOHN MILLARD SO WE

5645
03:24:19,439 --> 03:24:20,841
ARE TAKING B CELLS AND ENG

5646
03:24:20,841 --> 03:24:23,043
FEARING THEM TO MAKE COMPLETELY

5647
03:24:23,043 --> 03:24:23,910
CUSTOMIZED MOLECULES.

5648
03:24:23,910 --> 03:24:27,614
AND THE IDEA HERE IS THAT WE

5649
03:24:27,614 --> 03:24:29,716
COULD THEN PUT THEM INTO AN

5650
03:24:29,716 --> 03:24:31,251
ANIMAL OR A HUMAN AND THEN

5651
03:24:31,251 --> 03:24:34,421
VACCINATE WITH GP120 BECAUSE

5652
03:24:34,421 --> 03:24:36,590
UNLIKE EXPRESSING AN ANTIBODY

5653
03:24:36,590 --> 03:24:38,024
FROM, SAY, MUSCLE, AND IF YOU

5654
03:24:38,024 --> 03:24:40,760
EXPRESS THE ANTIBODY FROM THE

5655
03:24:40,760 --> 03:24:44,297
AUTHENTIC ANTIBODY LOCUS,

5656
03:24:44,297 --> 03:24:45,465
IMMUNOGLOBULIN LOCUS IN B CELLS,

5657
03:24:45,465 --> 03:24:46,800
YOU HAVE THE POTENTIAL FOR THAT

5658
03:24:46,800 --> 03:24:47,968
ANTIBODY TO RESPOND TOITY

5659
03:24:47,968 --> 03:24:52,038
VACCINTO ITSVACCINE AND PROVIDEM

5660
03:24:52,038 --> 03:24:53,673
SECRETION OF THE ANTIBODY.

5661
03:24:53,673 --> 03:24:57,410
BECAUSE WE'RE USING AN SIVMAC

5662
03:24:57,410 --> 03:25:00,213
239 MODEL, WE HAD TO DEVELOP

5663
03:25:00,213 --> 03:25:01,381
CANDIDATE ANTIBODIES THAT WOULD

5664
03:25:01,381 --> 03:25:02,215
WORK IN THIS SYSTEM.

5665
03:25:02,215 --> 03:25:06,453
SO USING THE SERIES OF BNABs

5666
03:25:06,453 --> 03:25:08,555
RECENTLY IDENTIFIED BY MARIO, WE

5667
03:25:08,555 --> 03:25:11,391
DERIVED OUR OWN VERSION OF

5668
03:25:11,391 --> 03:25:12,459
ITS103 THAT'S SHOWN ON THE LEFT,

5669
03:25:12,459 --> 03:25:16,096
AND WE ALSO PLAYED AROUND WITH

5670
03:25:16,096 --> 03:25:17,731
ECD4IG AND DID A SORT OF MIX AND

5671
03:25:17,731 --> 03:25:19,065
MATCH AND FOUND THE BEST VERSION

5672
03:25:19,065 --> 03:25:22,102
OF THE MOLECULE THAT WORKED

5673
03:25:22,102 --> 03:25:23,537
AGAINST SIVMAC 239.

5674
03:25:23,537 --> 03:25:24,738
BUT THEN IMPORTANTLY WE WERE

5675
03:25:24,738 --> 03:25:25,605
ALSO ABLE TO COMBINE THIS

5676
03:25:25,605 --> 03:25:27,307
THROUGH OUR EDITING TECHNOLOGY

5677
03:25:27,307 --> 03:25:30,544
WITH CHANGES IN THE FC PORTION

5678
03:25:30,544 --> 03:25:31,378
OF THE ANTIBODY.

5679
03:25:31,378 --> 03:25:32,846
SO WE'VE INCORPORATED SOME

5680
03:25:32,846 --> 03:25:35,682
MUTATIONS THAT ARE KNOWN TO

5681
03:25:35,682 --> 03:25:38,618
ENHANCE ADC SEQ KILLING BY NK

5682
03:25:38,618 --> 03:25:39,719
CELLS AND THE GRAPH SHOWS YOU

5683
03:25:39,719 --> 03:25:41,454
DOWN AT THE BOTTOM IN RED, THIS

5684
03:25:41,454 --> 03:25:43,323
IS OUR SORT OF OPTIMIZED

5685
03:25:43,323 --> 03:25:44,424
ANTIBODY THAT ALSO CONTAINS

5686
03:25:44,424 --> 03:25:48,461
THESE MUTATIONS.

5687
03:25:48,461 --> 03:25:50,397
THE FINAL COMPONENT OF RF 3 IS

5688
03:25:50,397 --> 03:25:52,065
USING BASE EDITORS WHICH ARE A

5689
03:25:52,065 --> 03:25:53,934
POTENTIALLY SAFER FORM OF

5690
03:25:53,934 --> 03:25:55,902
CRISPR/CAS 9 TO TARGET THE HIV

5691
03:25:55,902 --> 03:25:59,272
GENOME, AND THIS IS WORK DONE

5692
03:25:59,272 --> 03:26:00,173
WITH ROSS WILSON.

5693
03:26:00,173 --> 03:26:02,042
SO WE'VE IDENTIFIED A COUPLE OF

5694
03:26:02,042 --> 03:26:04,978
SEQUENCES, WE REALLY LIKE THE

5695
03:26:04,978 --> 03:26:06,613
TATTER BOX AND THE LTRs IN

5696
03:26:06,613 --> 03:26:12,185
BOTH HIV AND SIEVE A SIV AS A SO

5697
03:26:12,185 --> 03:26:16,923
TARGET.

5698
03:26:16,923 --> 03:26:18,525
OUR APPROACH, TRYING TWO

5699
03:26:18,525 --> 03:26:19,859
DIFFERENT WAYS OF THINKING ABOUT

5700
03:26:19,859 --> 03:26:23,229
DELIVERING THESE BASE EDITORS IN

5701
03:26:23,229 --> 03:26:23,563
VIVO.

5702
03:26:23,563 --> 03:26:24,864
ONE APPROACH IS TO PACKAGE THEM

5703
03:26:24,864 --> 03:26:27,334
INTO A RETROVIRAL PARTICLE OR A

5704
03:26:27,334 --> 03:26:27,767
VLP.

5705
03:26:27,767 --> 03:26:29,836
AND THE SECOND APPROACH IS TO

5706
03:26:29,836 --> 03:26:32,806
MAKE THEM AS A KIND OF

5707
03:26:32,806 --> 03:26:33,573
RECOMBINANT COMBINATION PROTEIN

5708
03:26:33,573 --> 03:26:34,874
AND YOU'LL SEE HERE I'M SHOWING

5709
03:26:34,874 --> 03:26:36,409
YOU THE LEVEL OF EDITING WE CAN

5710
03:26:36,409 --> 03:26:38,912
GET WHEN WE ADD EITHER THE

5711
03:26:38,912 --> 03:26:42,649
VLPs TO DELIVER THE BASE

5712
03:26:42,649 --> 03:26:44,150
EDITORS OR THE RECOMBINANT

5713
03:26:44,150 --> 03:26:44,384
PROTEIN.

5714
03:26:44,384 --> 03:26:46,620
WITH THE RECOMBINANT PROTEIN, WE

5715
03:26:46,620 --> 03:26:48,455
ALSO SIGNIFICANTLY INCREASE ED

5716
03:26:48,455 --> 03:26:49,756
ILTING WHEN WE ADD A CELL

5717
03:26:49,756 --> 03:26:51,524
PENETRATING PEPTIDE.

5718
03:26:51,524 --> 03:26:52,192
THEN OF COURSE MOST IMPORTANT

5719
03:26:52,192 --> 03:26:53,493
THE DIFFICULT AND CHALLENGING

5720
03:26:53,493 --> 03:26:55,128
THING IS HOW THE HECK DO WE

5721
03:26:55,128 --> 03:26:57,197
TARGET A CD4 T-CELL IN VIVO.

5722
03:26:57,197 --> 03:26:58,632
SO TO THAT END, WE'RE TRYING TWO

5723
03:26:58,632 --> 03:27:00,166
DIFFERENT APPROACHES WITH THESE

5724
03:27:00,166 --> 03:27:01,334
TWO DIFFERENT DELIVERY SYSTEMS,

5725
03:27:01,334 --> 03:27:02,769
AND FOR EXAMPLE, I'M SHOWING

5726
03:27:02,769 --> 03:27:05,305
HERE THAT WE ARE ABLE TO

5727
03:27:05,305 --> 03:27:07,140
EXQUISITELY TARGET RESTING

5728
03:27:07,140 --> 03:27:09,776
CD4 T-CELLS WITH OUR RETROVIRAL

5729
03:27:09,776 --> 03:27:10,810
PARTICLES, AND WE HAVE WORK IN

5730
03:27:10,810 --> 03:27:14,280
PROGRESS MAKING THE COMBINATION

5731
03:27:14,280 --> 03:27:15,815
TO TARGET T-CELLS BY ADDING A

5732
03:27:15,815 --> 03:27:18,318
LIGAND TO THOSE.

5733
03:27:18,318 --> 03:27:19,519
WITH THAT, I WILL FINISH.

5734
03:27:19,519 --> 03:27:20,520
THESE ARE THE NAMES OF THE

5735
03:27:20,520 --> 03:27:22,555
PEOPLE INVOLVED IN THE FOUR

5736
03:27:22,555 --> 03:27:23,657
DIFFERENT PROJECTS AND I'M HAPPY

5737
03:27:23,657 --> 03:27:25,992
TO PASS ON TO OUR COMMUNITY

5738
03:27:25,992 --> 03:27:26,526
ENGAGEMENT REPRESENTATIVE.

5739
03:27:26,526 --> 03:27:29,996
[APPLAUSE]

5740
03:27:29,996 --> 03:27:32,332
PRAWSH

5741
03:27:32,332 --> 03:27:34,267
>> GOOD AFTERNOON,
EVERYONE.

5742
03:27:34,267 --> 03:27:36,236
I'M JEFF TAYLOR.

5743
03:27:36,236 --> 03:27:37,570
YOU MAY NOT RECOGNIZE ME BECAUSE

5744
03:27:37,570 --> 03:27:40,774
I SHAVED MY BEARD.

5745
03:27:40,774 --> 03:27:41,875
AS YOU'VE HEARD, JEFF IS NOT

5746
03:27:41,875 --> 03:27:44,310
WITH US UNFORTUNATELY TODAY, BUT

5747
03:27:44,310 --> 03:27:47,313
I AM ANDY CATES, ONE OF THE

5748
03:27:47,313 --> 03:27:49,749
CO-CHAIRS OF THE RID HIV

5749
03:27:49,749 --> 03:27:50,250
COLLABORATORY, COMMUNITY

5750
03:27:50,250 --> 03:27:53,887
ADVISORY BOARD, AND HELLO.

5751
03:27:53,887 --> 03:27:58,491
THERE'S A WIND UP HERE.

5752
03:27:58,491 --> 03:28:00,994
SO RID HIV, WE'RE KIND OF A FUN

5753
03:28:00,994 --> 03:28:01,561
CAB.

5754
03:28:01,561 --> 03:28:04,364
WE HAVE DONE SOME PRETTY NEAT

5755
03:28:04,364 --> 03:28:04,731
THINGS TOO.

5756
03:28:04,731 --> 03:28:10,070
SO THE MDC CAB LANGUAGE

5757
03:28:10,070 --> 03:28:12,706
GUIDELINES, WE HAD PRESENTED AT

5758
03:28:12,706 --> 03:28:14,240
IAS LANGUAGE AS YOU'LL HEAR IS

5759
03:28:14,240 --> 03:28:17,310
SOMETHING THAT WE'VE CONTINUALLY

5760
03:28:17,310 --> 03:28:18,378
BEEN HARPING ABOUT FOR MANY,

5761
03:28:18,378 --> 03:28:26,486
MANY YEARS, AND ALSO BRIDGETTE

5762
03:28:26,486 --> 03:28:30,090
PICOU PRESENTED AT USCHA ON A

5763
03:28:30,090 --> 03:28:33,693
HALF DAY CURE SESSION WITH DARE,

5764
03:28:33,693 --> 03:28:35,128
CRISPR FOR CURE AND THE REUNION

5765
03:28:35,128 --> 03:28:35,428
PROJECT.

5766
03:28:35,428 --> 03:28:37,330
THEN WE DID A LONG TERM SURVIVOR

5767
03:28:37,330 --> 03:28:38,298
WEBINAR SERIES, WHICH I THINK

5768
03:28:38,298 --> 03:28:39,833
YOU'VE HEARD A LOT ABOUT.

5769
03:28:39,833 --> 03:28:42,335
THERE'S BEEN SEVERAL

5770
03:28:42,335 --> 03:28:43,103
COLLABORATORIES THAT HAVE

5771
03:28:43,103 --> 03:28:47,173
PRESENTED THAT.

5772
03:28:47,173 --> 03:28:48,475
BACK TO LANGUAGE, BEFORE I

5773
03:28:48,475 --> 03:28:52,645
REALLY DIG INTO THIS, I WONDER

5774
03:28:52,645 --> 03:28:54,380
IF YOU'D KIND OF INDULGE ME FOR

5775
03:28:54,380 --> 03:28:55,915
A SECOND, MAYBE LOOK AROUND THE

5776
03:28:55,915 --> 03:28:57,884
ROOM AT WHO'S IN HERE, JUST KIND

5777
03:28:57,884 --> 03:28:59,185
OF LOOK AROUND THE ROOM AND

5778
03:28:59,185 --> 03:29:00,086
IMAGINE YOU'RE THE ONLY PERSON

5779
03:29:00,086 --> 03:29:02,589
IN HERE THAT IS NOT AN INFECTED

5780
03:29:02,589 --> 03:29:08,161
SUBJECT.

5781
03:29:08,161 --> 03:29:09,462
THEN FLIP THAT AND THINK ABOUT

5782
03:29:09,462 --> 03:29:10,463
EVERYBODY ELSE IN THIS ROOM

5783
03:29:10,463 --> 03:29:12,098
BEING AN INFECTED SUBJECT, AND

5784
03:29:12,098 --> 03:29:13,967
YOU'RE THE ONLY ONE THAT'S NOT

5785
03:29:13,967 --> 03:29:16,035
INFECTED.

5786
03:29:16,035 --> 03:29:17,804
DID THAT, LIKE, REGISTER?

5787
03:29:17,804 --> 03:29:20,740
I MEAN, I'M HOPING IT KIND OF

5788
03:29:20,740 --> 03:29:22,709
GAVE PEOPLE A VISCERAL REACTION.

5789
03:29:22,709 --> 03:29:24,377
I DIDN'T INTEND TO, LIKE, BRING

5790
03:29:24,377 --> 03:29:27,447
THINGS THIS DIRECTION, BUT ONE

5791
03:29:27,447 --> 03:29:31,050
OF THE CAB MEMBERS SHOWED ME

5792
03:29:31,050 --> 03:29:34,220
THIS FLYER THAT'S OUTSIDE.

5793
03:29:34,220 --> 03:29:35,622
AND THE INCLUSION CRITERIA FOR

5794
03:29:35,622 --> 03:29:37,590
THIS RESEARCH STUDY IS THE VERY

5795
03:29:37,590 --> 03:29:40,994
FIRST BULLET, HIV-1 INFECTED

5796
03:29:40,994 --> 03:29:43,029
THIS IS FROM THE NIH, AND THE

5797
03:29:43,029 --> 03:29:44,497
NIH IS THE ONE THAT'S BEEN

5798
03:29:44,497 --> 03:29:46,699
TELLING US NOT TO USE THIS

5799
03:29:46,699 --> 03:29:47,467
LANGUAGE.

5800
03:29:47,467 --> 03:29:49,669
SO ANYWAY, FOOD FOR THOUGHT.

5801
03:29:49,669 --> 03:29:52,071
MOVING ON.

5802
03:29:52,071 --> 03:29:53,940
SO WE DID UPDATE THE COMMUNITY

5803
03:29:53,940 --> 03:29:57,343
PREFERRED LANGUAGE, AND THAT'S,

5804
03:29:57,343 --> 03:29:58,978
AS YOU KNOW, A GOAL OF MAKING

5805
03:29:58,978 --> 03:30:01,848
PEOPLE FEEL, WELL, HUMAN.

5806
03:30:01,848 --> 03:30:06,986
AND NOT INFECTED OR SUBJECTED.

5807
03:30:06,986 --> 03:30:08,288
I WILL LEAVE IT AT THAT BECAUSE

5808
03:30:08,288 --> 03:30:11,157
I THINK MY POINT IS MADE.

5809
03:30:11,157 --> 03:30:13,660
SORRY TO BE A DRAG AFTER LUNCH.

5810
03:30:13,660 --> 03:30:17,597
THIS IS THE WEBINAR SERIES THAT

5811
03:30:17,597 --> 03:30:18,731
I'M SURE EVERYBODY HAS SEEN

5812
03:30:18,731 --> 03:30:20,233
ENOUGH TIMES THAT YOU'VE

5813
03:30:20,233 --> 03:30:21,568
MEMORIZED THE DATES AND YOU'RE

5814
03:30:21,568 --> 03:30:22,969
GOING TO JOIN US IN THE NEXT

5815
03:30:22,969 --> 03:30:23,536
ONES.

5816
03:30:23,536 --> 03:30:25,071
THE NEXT ONE IS OCTOBER 24TH,

5817
03:30:25,071 --> 03:30:26,272
AND THAT'S THE PARTICIPANT

5818
03:30:26,272 --> 03:30:27,273
EXPERIENCES IN RESEARCH, WHERE

5819
03:30:27,273 --> 03:30:29,776
WE'RE GOING TO HAVE PAUL

5820
03:30:29,776 --> 03:30:32,412
EDMONDS, MATT SHARPE AND TOM

5821
03:30:32,412 --> 03:30:33,847
VILLA ALONG WITH GAIL GRAHAM

5822
03:30:33,847 --> 03:30:34,948
TALKING ABOUT THEIR EXPERIENCES

5823
03:30:34,948 --> 03:30:37,350
IN RESEARCH.

5824
03:30:37,350 --> 03:30:40,420
I KNOW TIME IS KIND OF SHORT FOR

5825
03:30:40,420 --> 03:30:43,022
US, SO IN MY LAST SLIDE, I WILL

5826
03:30:43,022 --> 03:30:47,427
GO OVER OUR FUTURE COMMUNITY

5827
03:30:47,427 --> 03:30:48,294
ENGAGEMENT ACTIVITIES THAT WE'VE

5828
03:30:48,294 --> 03:30:48,828
GOT PLANNED.

5829
03:30:48,828 --> 03:30:50,029
SO MANY OF YOU HOPEFULLY ALL OF

5830
03:30:50,029 --> 03:30:53,233
YOU HAVE HEARD OF THE LAST GIFT

5831
03:30:53,233 --> 03:30:56,069
STUDY, WHICH IS SOMETHING THAT

5832
03:30:56,069 --> 03:30:57,604
HAS GENERATED AN AWFUL LOT OF

5833
03:30:57,604 --> 03:30:58,271
GREAT DATA.

5834
03:30:58,271 --> 03:31:02,208
ALL COMING FROM AMAZINGLY AL

5835
03:31:02,208 --> 03:31:06,679
TRUE IS ALTRUISTIC PARTICIPANTST

5836
03:31:06,679 --> 03:31:07,180
JOINED THIS STUDY.

5837
03:31:07,180 --> 03:31:09,549
IT'S CONTINUING TO GO ON AND ON

5838
03:31:09,549 --> 03:31:10,149
NOVEMBER 6TH, WE'RE GOING TO

5839
03:31:10,149 --> 03:31:11,317
HAVE A COMMUNITY CONSULTATION

5840
03:31:11,317 --> 03:31:12,151
EVENT WHERE THE COMMUNITY, WHO

5841
03:31:12,151 --> 03:31:13,519
IS A LARGE, LARGE PART OF THIS

5842
03:31:13,519 --> 03:31:16,356
STUDY, WE HELPED FORM THE STUDY,

5843
03:31:16,356 --> 03:31:17,991
WE WERE CONSULTED EVERY SINGLE

5844
03:31:17,991 --> 03:31:19,425
STEP OF THE WAY AND NOW WE'RE

5845
03:31:19,425 --> 03:31:24,230
BEING CONSULTED AGAIN.

5846
03:31:24,230 --> 03:31:26,099
SO IT IS DEFINITELY ONE OF THOSE

5847
03:31:26,099 --> 03:31:29,602
THINGS THAT IS FOR US, WITH US.

5848
03:31:29,602 --> 03:31:31,471
THEN ON WORLD AIDS DAY, WE'VE

5849
03:31:31,471 --> 03:31:34,207
GOT THE TIMOTHY RAY BROWN

5850
03:31:34,207 --> 03:31:35,108
COMMUNITY CURE SYMPOSIUM.

5851
03:31:35,108 --> 03:31:36,442
THIS WILL BE THE SECOND ONE THAT

5852
03:31:36,442 --> 03:31:38,745
WE'VE DONE.

5853
03:31:38,745 --> 03:31:41,581
DR. CANNON AND CHANDA WILL BE

5854
03:31:41,581 --> 03:31:43,650
HERE, OR THERE IN PALM SPRINGS.

5855
03:31:43,650 --> 03:31:46,386
WE'LL ALSO HAVE JOHN ZAIA FROM

5856
03:31:46,386 --> 03:31:47,954
THE CITY OF HOPE AND OUR OWN

5857
03:31:47,954 --> 03:31:49,923
PAUL EDMONDS, THE CITY OF HOPE

5858
03:31:49,923 --> 03:31:50,356
PATIENT.

5859
03:31:50,356 --> 03:31:55,495
THEN WE HAVE A CONTINUING VIRAL

5860
03:31:55,495 --> 03:31:58,131
RESERVOIR WEBINAR SERIES ALSO

5861
03:31:58,131 --> 03:31:59,432
DONE WITH DARE AND CRISPR AND

5862
03:31:59,432 --> 03:32:02,635
CURE TREATMENT -- CURE AND THE

5863
03:32:02,635 --> 03:32:04,604
TREATMENT ACTION GROUP.

5864
03:32:04,604 --> 03:32:07,240
THESE ARE REALLY WELL, WELL

5865
03:32:07,240 --> 03:32:10,843
ATTENDED WEBINARS.

5866
03:32:10,843 --> 03:32:12,478
YOU'VE HEARD SOME OF THE NUMBERS

5867
03:32:12,478 --> 03:32:13,379
BEFORE BUT THERE'S PEOPLE

5868
03:32:13,379 --> 03:32:14,580
LOOKING AT THESE WEBINARS FROM

5869
03:32:14,580 --> 03:32:15,114
ALL OVER THE WORLD.

5870
03:32:15,114 --> 03:32:16,316
IT'S REALLY HEARTENING.

5871
03:32:16,316 --> 03:32:21,454
THEN WE DO A PRECROI COMMUNITY

5872
03:32:21,454 --> 03:32:22,221
CURE WORKSHOP.

5873
03:32:22,221 --> 03:32:22,989
THAT'S SOMETHING THAT'S BEEN

5874
03:32:22,989 --> 03:32:23,656
HAPPENING FOR YEARS.

5875
03:32:23,656 --> 03:32:25,425
WE GET SOME OF THE MOST

5876
03:32:25,425 --> 03:32:29,562
IMPRESSIVE PRESENTATIONS

5877
03:32:29,562 --> 03:32:31,197
DIRECTLY TO THE COMMUNITY PRIOR

5878
03:32:31,197 --> 03:32:34,600
TO THE DAY BEFORE CROI.

5879
03:32:34,600 --> 03:32:35,501
WE'VE ALSO COME UP WITH THE IDEA

5880
03:32:35,501 --> 03:32:38,638
OF DOING A SPANISH LANGUAGE

5881
03:32:38,638 --> 03:32:39,973
RESERVOIR, AND IT'S GOING TO

5882
03:32:39,973 --> 03:32:45,011
FEATURE THE LONDON PATIENT, ADAM

5883
03:32:45,011 --> 03:32:46,012
CASTILLEJO, SO THAT'S KIND OF

5884
03:32:46,012 --> 03:32:46,279
COOL.

5885
03:32:46,279 --> 03:32:47,480
WE DO HAVE SPANISH IN THIS WORLD

5886
03:32:47,480 --> 03:32:48,781
AND IT'S ABOUT TIME THAT WE'VE

5887
03:32:48,781 --> 03:32:50,316
STARTED REALLY REACHING OUT TO

5888
03:32:50,316 --> 03:32:53,286
FOLKS THAT SPEAK SPANISH

5889
03:32:53,286 --> 03:32:59,292
LANGUAGES AND WE'RE GOING TO BE

5890
03:32:59,292 --> 03:33:00,626
DOING THAT -- I'M NOT EXACTLY

5891
03:33:00,626 --> 03:33:01,894
SURE ON THE DATE BUT IT COMING

5892
03:33:01,894 --> 03:33:02,595
UP FAIRLY SOON.

5893
03:33:02,595 --> 03:33:05,431
AND THEN THE LONG TERM SURVIVOR

5894
03:33:05,431 --> 03:33:07,333
WEBINAR SERIES CONTINUES.

5895
03:33:07,333 --> 03:33:11,237
WITH MORE COLLABORATIONS FROM

5896
03:33:11,237 --> 03:33:17,176
DARE, CHRIS TER FO CHRIS TE CRID

5897
03:33:17,176 --> 03:33:19,045
THAT'S GOING TO BE GOING ON IN

5898
03:33:19,045 --> 03:33:20,346
THE WILL END OF THE YEAR.

5899
03:33:20,346 --> 03:33:21,681
SO ANYWAY I'VE GOT ABOUT

5900
03:33:21,681 --> 03:33:22,882
26 SECONDS TO LEAVE YOU WITH,

5901
03:33:22,882 --> 03:33:23,983
AND I THANK YOU FOR YOUR

5902
03:33:23,983 --> 03:33:24,250
ATTENTION.

5903
03:33:24,250 --> 03:33:29,555
[APPLAUSE]

5904
03:33:29,555 --> 03:33:32,959
>> THANK YOU, TEAM RID,
EXACT

5905
03:33:32,959 --> 03:33:33,393
TIME, 40 MINUTES.

5906
03:33:33,393 --> 03:33:36,229
SO I APPRECIATE THAT.

5907
03:33:36,229 --> 03:33:37,530
THE SESSION IS NOW OPEN FOR

5908
03:33:37,530 --> 03:33:46,305
QUESTIONS AND ANSWERS.

5909
03:33:46,305 --> 03:33:46,839
GO YOU A HEAD.

5910
03:33:46,839 --> 03:33:51,244
>> HI, KIRA FROM UMASS.

5911
03:33:51,244 --> 03:33:53,112
I CAN'T SEE YOUR NAME TAG FROM

5912
03:33:53,112 --> 03:33:53,646
HERE.

5913
03:33:53,646 --> 03:33:56,816
I THINK IT'S ASHISH.

5914
03:33:56,816 --> 03:33:58,251
CLARIFICATION ON ONE OF YOUR

5915
03:33:58,251 --> 03:33:58,484
SLIDES.

5916
03:33:58,484 --> 03:34:00,319
WHEN YOU TALKED ABOUT THE LACTO,

5917
03:34:00,319 --> 03:34:01,854
I THOUGHT THAT WAS REALLY

5918
03:34:01,854 --> 03:34:02,188
INTERESTING.

5919
03:34:02,188 --> 03:34:04,690
IS THE LACTO IN THE PLASMA OR IS

5920
03:34:04,690 --> 03:34:06,659
IT THE LACTO IN THE GUT THAT

5921
03:34:06,659 --> 03:34:07,226
CORRELATED WITH --

5922
03:34:07,226 --> 03:34:12,799
>> NO, SO WE DID PAT SEQ,
IT'S A

5923
03:34:12,799 --> 03:34:18,604
PLASMA QUANTIFICATION -- WHICH

5924
03:34:18,604 --> 03:34:21,107
WAS A PLASMA QUANTIFICATION OF

5925
03:34:21,107 --> 03:34:22,842
MICROBIAL READS, AND WE MAP THAT

5926
03:34:22,842 --> 03:34:25,611
TO THE LACTOBACILLUS GENUS, AND

5927
03:34:25,611 --> 03:34:27,880
THEN TO BREAK DOWN THE SPECIES

5928
03:34:27,880 --> 03:34:30,616
CLUSTER, WE DID AN UNBIASED

5929
03:34:30,616 --> 03:34:35,655
SCREEN OF ALL KNOWN GUT

5930
03:34:35,655 --> 03:34:36,322
LACTOBACILLI.

5931
03:34:36,322 --> 03:34:40,827
THE TOP 14.

5932
03:34:40,827 --> 03:34:43,863
WE SAW THE ONES KNOWN TO BE LESS

5933
03:34:43,863 --> 03:34:45,198
ABUNDANT IN HUMANS WERE THE ONES

5934
03:34:45,198 --> 03:34:48,267
THAT PROMOTED TGF BETA

5935
03:34:48,267 --> 03:34:49,569
PRODUCTION AND IMMUNE

5936
03:34:49,569 --> 03:34:49,869
DYSFUNCTION.

5937
03:34:49,869 --> 03:34:51,337
>> SO YOU'RE ASSUMING THAT
COMES

5938
03:34:51,337 --> 03:34:52,772
FROM THE BACTERIUM THAT'S IN THE

5939
03:34:52,772 --> 03:34:53,840
PERIPHERY, IN THE BLOOD, AM I

5940
03:34:53,840 --> 03:34:54,073
CORRECT?

5941
03:34:54,073 --> 03:34:56,909
>> NO, THEY'RE JUST
MICROBIAL

5942
03:34:56,909 --> 03:34:59,412
READS, SO THEY'RE AN ARTIFACT OF

5943
03:34:59,412 --> 03:35:02,615
THE CROSSTALK BETWEEN THE IMMUNE

5944
03:35:02,615 --> 03:35:04,584
SYSTEM AND THE BACTERIA AT THE

5945
03:35:04,584 --> 03:35:04,817
MUCOSA.

5946
03:35:04,817 --> 03:35:06,986
>> OKAY, PERFECT.

5947
03:35:06,986 --> 03:35:09,388
>> SO QUESTION FOR RAFICK.

5948
03:35:09,388 --> 03:35:12,225
IN THE INTERFERONS, DID YOU SEE

5949
03:35:12,225 --> 03:35:15,294
ANY DIFFERENCE BETWEEN THE ALPHA

5950
03:35:15,294 --> 03:35:16,395
ISOTYPES AND BETA WHEN IT CAME

5951
03:35:16,395 --> 03:35:18,197
TO THE INTERFERON SIGNATURE, AND

5952
03:35:18,197 --> 03:35:19,932
THEN THE SECOND PART IS, IS IT

5953
03:35:19,932 --> 03:35:22,101
ALL COMING FROM THE MYELOID CELL

5954
03:35:22,101 --> 03:35:23,536
OR ARE THERE OTHER CELLS

5955
03:35:23,536 --> 03:35:26,272
CONTRIBUTING TO THE TYPE I

5956
03:35:26,272 --> 03:35:31,010
INTERFERON PRODUCTION?

5957
03:35:31,010 --> 03:35:33,479
>> SO THE FIRST PART OF
YOUR

5958
03:35:33,479 --> 03:35:36,449
QUESTION, IT'S MOST LEEWAY TA,

5959
03:35:36,449 --> 03:35:37,116
ALPHA.

5960
03:35:37,116 --> 03:35:45,758
IN VITRO, THE -- BUT TO MEASURE

5961
03:35:45,758 --> 03:35:50,029
IN VITRO WE SEE CLEAR ALPHA

5962
03:35:50,029 --> 03:35:51,130
VERSUS BETA SIGNATURE.

5963
03:35:51,130 --> 03:35:52,465
THERE'S HUGE OVERLAP BETWEEN

5964
03:35:52,465 --> 03:35:54,634
ALPHA AND BETA SIGNATURE, BUT

5965
03:35:54,634 --> 03:35:56,936
WHAT WE KNOW IS IT'S REALLY A

5966
03:35:56,936 --> 03:35:59,906
BETA WHICH -- REALLY DRIVING

5967
03:35:59,906 --> 03:36:02,842
BETA INTERFERON AND -- SO THAT'S

5968
03:36:02,842 --> 03:36:03,943
THE FIRST QUESTION.

5969
03:36:03,943 --> 03:36:10,950
THE SECOND ONE WAS?

5970
03:36:10,950 --> 03:36:15,888
ANY CELL CAN MAKE IT.

5971
03:36:15,888 --> 03:36:18,291
 -- HAVE SHOWN THAT -- CAN

5972
03:36:18,291 --> 03:36:20,493
TRIGGER -- KEYSTONE MEETING

5973
03:36:20,493 --> 03:36:23,095
WHERE AGAIN THERE WAS A HUGE

5974
03:36:23,095 --> 03:36:26,832
EMPHASIS -- CAN BE SENSORS OF --

5975
03:36:26,832 --> 03:36:32,405
OR BACTERIA, SO IT CAN BE --

5976
03:36:32,405 --> 03:36:35,708
CELLS, BUT WE HAVE TO

5977
03:36:35,708 --> 03:36:37,009
DEMONSTRATE THAT POINT BUT WE

5978
03:36:37,009 --> 03:36:38,878
ALSO SHOW THAT IN VITRO, AT

5979
03:36:38,878 --> 03:36:41,847
LEAST, BILE ACID CAN TRIGGER --

5980
03:36:41,847 --> 03:36:44,517
INTERFERON BETA BOTH IN

5981
03:36:44,517 --> 03:36:46,919
DIFFERENT -- AND EVEN IN NAIVE

5982
03:36:46,919 --> 03:36:49,322
CELLS, NAIVE T-CELLS.

5983
03:36:49,322 --> 03:36:53,059
SO IN VIVO, I THINK WE NEED T

5984
03:36:53,059 --> 03:36:57,330
TO -- TO DEMONSTRATE THAT.

5985
03:36:57,330 --> 03:36:59,198
>> WE CAN TAKE A FEW MORE

5986
03:36:59,198 --> 03:37:02,368
QUESTIONS.

5987
03:37:02,368 --> 03:37:04,003
>> QUICK QUESTION FOR

5988
03:37:04,003 --> 03:37:04,337
DR. CANNON.

5989
03:37:04,337 --> 03:37:06,272
I WAS REALLY CURIOUS ON YOUR B

5990
03:37:06,272 --> 03:37:09,041
CELL EDITING APPROACH.

5991
03:37:09,041 --> 03:37:10,910
I KNOW YOU'RE DELIVERING THE

5992
03:37:10,910 --> 03:37:13,646
REPAIR TEMPLATE WITH AN AAV AND

5993
03:37:13,646 --> 03:37:14,413
ELECTROPLATING CRISPR, BUT CAN

5994
03:37:14,413 --> 03:37:18,484
YOU TALK MORE ABOUT THOSE CELLS?

5995
03:37:18,484 --> 03:37:20,319
DO THEY STILL HAVE TO GO THROUGH

5996
03:37:20,319 --> 03:37:21,887
SOME TYPE OF -- I'M CURIOUS

5997
03:37:21,887 --> 03:37:24,557
EXACTLY ABOUT THE STRATEGY THE 

5998
03:37:24,557 --> 03:37:25,491
THERE.

5999
03:37:25,491 --> 03:37:26,926
>> SORRY, I DIDN'T QUITE
GET

6000
03:37:26,926 --> 03:37:27,994
WHAT YOU SAID TOWARDS THE END.

6001
03:37:27,994 --> 03:37:30,429
>> I WAS JUST WONDERING
ONCE YOU

6002
03:37:30,429 --> 03:37:33,266
BASE KR HAVE YOUR TEMPLATE, GOT

6003
03:37:33,266 --> 03:37:34,700
YOUR CRISPR, YOU TARGET THE B

6004
03:37:34,700 --> 03:37:37,003
CELL LOCUS AND INTRODUCE YOUR

6005
03:37:37,003 --> 03:37:38,404
ANTIBODY, ONCE THAT B CELL IS

6006
03:37:38,404 --> 03:37:42,041
THEN PUT BACK INTO AN ANIMAL, IS

6007
03:37:42,041 --> 03:37:44,343
THAT ANTIBODY -- DOES THAT GO

6008
03:37:44,343 --> 03:37:45,978
THROUGH -- DOES IT GO THROUGH --

6009
03:37:45,978 --> 03:37:47,079
BASICALLY, ONCE YOU'VE MODIFIED

6010
03:37:47,079 --> 03:37:48,414
THE B CELL LOCUS IN THAT

6011
03:37:48,414 --> 03:37:48,814
PARTICULAR WAY?

6012
03:37:48,814 --> 03:37:51,017
>> OKAY.

6013
03:37:51,017 --> 03:37:53,619
SO THAT'S OUR THINKING, IS THAT

6014
03:37:53,619 --> 03:37:56,722
BY INSERTING A B CELL INTO THE

6015
03:37:56,722 --> 03:37:57,723
AUTHENTIC IMMUNOGLOBULIN LOCUS,

6016
03:37:57,723 --> 03:37:59,191
WE CAN HOPEFULLY RESERVE ALL THE

6017
03:37:59,191 --> 03:38:00,893
SORT OF NATURAL FEATURES OF B

6018
03:38:00,893 --> 03:38:05,364
CELLS AND ANTIBODY PRODUCTION.

6019
03:38:05,364 --> 03:38:07,800
SO WHAT WE'VE SEEN IS WE TAKE

6020
03:38:07,800 --> 03:38:10,002
THE B CELLS AND DIFFERENTIATE

6021
03:38:10,002 --> 03:38:11,537
THEM TOWARDS PLASMA CELLS, TYPE

6022
03:38:11,537 --> 03:38:13,406
OF B CELL THAT CHURNS OUT

6023
03:38:13,406 --> 03:38:15,041
ANTIBODIES, THEY CHURN OUT THE

6024
03:38:15,041 --> 03:38:15,474
ANTIBODIES.

6025
03:38:15,474 --> 03:38:18,010
WE CAN ALSO PUT THEM INTO --

6026
03:38:18,010 --> 03:38:20,546
THERE'S A NICE MODEL OF

6027
03:38:20,546 --> 03:38:22,048
IMMUNIZATION IN VITRO WHICH IS

6028
03:38:22,048 --> 03:38:26,018
BASED ON TONSIL ORGANOIDS FROM

6029
03:38:26,018 --> 03:38:30,690
MARK DAVIS' GROUP, WITH ARE A

6030
03:38:30,690 --> 03:38:33,693
VACCINE BASICALLY GP120, THE

6031
03:38:33,693 --> 03:38:36,962
ENGINEERED CELLS RESPOND AND

6032
03:38:36,962 --> 03:38:44,437
EXPAND AND DIFFERENTIATE WHAT

6033
03:38:44,437 --> 03:38:47,406
ANTIBODIES DO, AND INDEED WE SEE

6034
03:38:47,406 --> 03:38:57,783
SIGNATURES OF SOMATIC

6035
03:44:47,633 --> 03:44:48,901
 THAT EXPERIMENT WAS ALSO

6036
03:44:48,901 --> 03:44:50,769
PUBLISHED VERY RECENTLY, IT TOOK

6037
03:44:50,769 --> 03:44:52,571
US A LITTLE BIT MORE THAN THREE

6038
03:44:52,571 --> 03:44:56,141
YEARS, I SHOULD SAY, TO COMPLETE

6039
03:44:56,141 --> 03:44:57,609
THIS BECAUSE WE HAVE TO REPEAT

6040
03:44:57,609 --> 03:44:59,912
MULTIPLE TIMES AND THEN THE RATE

6041
03:44:59,912 --> 03:45:02,081
OF THE SUCCESS OR NO REBOUND

6042
03:45:02,081 --> 03:45:05,084
INCREASED UP FOR CLOSE TO 50% OR

6043
03:45:05,084 --> 03:45:07,453
MORE.

6044
03:45:07,453 --> 03:45:11,623
SO THIS ALL TOGETHER IN

6045
03:45:11,623 --> 03:45:13,092
COLLABORATION WITH ANOTHER

6046
03:45:13,092 --> 03:45:17,229
GROUP, WE STARTED USING

6047
03:45:17,229 --> 03:45:18,931
NON-HUMAN PRIMATE.

6048
03:45:18,931 --> 03:45:20,799
AND THEN THE RESULT OF THAT

6049
03:45:20,799 --> 03:45:27,206
EXPERIMENT SHOWS THAT IN THE

6050
03:45:27,206 --> 03:45:28,574
LARGER GROUP OF ANIMAL SHOW THAT

6051
03:45:28,574 --> 03:45:31,410
AGAIN WHAT WE'VE GOT EARLIER WAS

6052
03:45:31,410 --> 03:45:35,481
REPRODUCIBLE AND THEN THE RESULT

6053
03:45:35,481 --> 03:45:37,850
IN THE DISSOLUTION OF THE VIRUS

6054
03:45:37,850 --> 03:45:47,693
CRISPR IN ALMOST EVERY TISSUE

6055
03:45:47,693 --> 03:45:49,328
AND ORGANISM BROAD RANGE

6056
03:45:49,328 --> 03:45:50,662
DISTRIBUTION AND FUNCTIONAL

6057
03:45:50,662 --> 03:45:52,865
INACTIVATION OF THE VIRUS.

6058
03:45:52,865 --> 03:45:55,901
SO WITH THAT INFORMATION, WE

6059
03:45:55,901 --> 03:46:00,072
DEVELOPED THE PROGRAM, MARTIN

6060
03:46:00,072 --> 03:46:03,542
DELANEY, WHICH COMPRISE THREE

6061
03:46:03,542 --> 03:46:07,513
RESEARCH FOCUS THAT THEY'RE --

6062
03:46:07,513 --> 03:46:11,550
MY COLLEAGUE DESCRIBED THAT, DO

6063
03:46:11,550 --> 03:46:13,585
YOU WANT TO PRESENT THIS ONE

6064
03:46:13,585 --> 03:46:14,386
BECAUSE IT'S A CONTINUATION OF

6065
03:46:14,386 --> 03:46:19,758
THE NEXT ONE.

6066
03:46:19,758 --> 03:46:21,160
>> WE ARE A NEW
COLLABORATORY.

6067
03:46:21,160 --> 03:46:23,262
WE HAVE AS EVERYONE ELSE THREE

6068
03:46:23,262 --> 03:46:28,167
RESEARCH FOCI, AND YOU CAN SEE

6069
03:46:28,167 --> 03:46:29,201
THE INTERACTIONS OF RESEARCH

6070
03:46:29,201 --> 03:46:29,501
FOCUS.

6071
03:46:29,501 --> 03:46:30,669
I THINK WE'RE A LITTLE BIT

6072
03:46:30,669 --> 03:46:31,470
SMALLER.

6073
03:46:31,470 --> 03:46:32,571
DELANEY AS FAR AS PI NUMBERS

6074
03:46:32,571 --> 03:46:38,510
THAN SOME OF THE OTHERS.

6075
03:46:38,510 --> 03:46:39,545
BUT VERY INTERACTIVE.

6076
03:46:39,545 --> 03:46:41,213
BASICALLY I WANTED TO GIVE A

6077
03:46:41,213 --> 03:46:42,815
LITTLE BIT OF OVERVIEW ON SOME

6078
03:46:42,815 --> 03:46:45,684
OF THE MODEL SYSTEMS THAT WE'RE

6079
03:46:45,684 --> 03:46:45,951
USING.

6080
03:46:45,951 --> 03:46:49,087
WE START FROM INSILICO, SO THIS

6081
03:46:49,087 --> 03:46:49,955
INCLUDES BIOINFORMATICS AND

6082
03:46:49,955 --> 03:46:50,956
COMPUTER BASED MODELING.

6083
03:46:50,956 --> 03:46:53,125
WE USE A LOT OF IN VITRO CELL

6084
03:46:53,125 --> 03:46:57,729
LINES, EX VIVO CLINICAL SAMPLES,

6085
03:46:57,729 --> 03:46:59,998
AND TWO DIFFERENT MICE MODEL, AN

6086
03:46:59,998 --> 03:47:08,674
IN VIVO HUMANIZED AN MO MODEL

6087
03:47:08,674 --> 03:47:10,976
AND ALSO A NOVEL MOUSE MODEL

6088
03:47:10,976 --> 03:47:11,944
WHICH I'LL TALK A LITTLE ABOUT

6089
03:47:11,944 --> 03:47:13,579
WHEN I TALK IN RETROVIRAL 2.

6090
03:47:13,579 --> 03:47:15,447
I'M IN OF COURSE NON-HUMAN

6091
03:47:15,447 --> 03:47:18,851
PRIMATES.

6092
03:47:18,851 --> 03:47:20,185
SO AS YOU WOULD GUESS FROM THE

6093
03:47:20,185 --> 03:47:22,821
NAME OF OUR COLLABORATORY, A LOT

6094
03:47:22,821 --> 03:47:24,957
OF OUR TECHNOLOGIES ARE BASED ON

6095
03:47:24,957 --> 03:47:25,424
CRISPR.

6096
03:47:25,424 --> 03:47:26,825
WE DO A LOT OF DIFFERENT THINGS

6097
03:47:26,825 --> 03:47:27,326
WITH CRISPR.

6098
03:47:27,326 --> 03:47:29,361
ONE IS FOR CRISPR MODIFICATION

6099
03:47:29,361 --> 03:47:32,064
OF IMMUNE CELLS AND THAT'S IN

6100
03:47:32,064 --> 03:47:33,732
RETROVIRAL 2, AND THEN

6101
03:47:33,732 --> 03:47:36,001
RETROVIRAL 3 IS REALLY LOOKING

6102
03:47:36,001 --> 03:47:37,269
AT THE ELIMINATION OF THE VIRAL

6103
03:47:37,269 --> 03:47:37,569
RESERVOIR.

6104
03:47:37,569 --> 03:47:39,838
SO WE TAKE KIND OF A MULTIPLEX

6105
03:47:39,838 --> 03:47:40,873
APPROACH IN ALL OF THESE WHERE

6106
03:47:40,873 --> 03:47:45,644
WE LOOK AT CRISPR MODIFICATION,

6107
03:47:45,644 --> 03:47:46,645
SELECTION OF THE GUIDE RNAs

6108
03:47:46,645 --> 03:47:48,247
AND THAT'S WHAT GIVES US THE

6109
03:47:48,247 --> 03:47:48,747
SPECIFICITY.

6110
03:47:48,747 --> 03:47:50,449
WE LOOK AT A NUMBER OF OFF

6111
03:47:50,449 --> 03:47:53,719
TARGET ASSESSMENTS AND THEN DO

6112
03:47:53,719 --> 03:47:55,153
EX VIVO EVALUATIONS OF

6113
03:47:55,153 --> 03:47:59,791
EFFICIENCY AND SPECIFICITY.

6114
03:47:59,791 --> 03:48:02,060
THIS INCLUDES BARCODED VIRAL

6115
03:48:02,060 --> 03:48:03,462
ANALYSIS WHICH WE USED IN

6116
03:48:03,462 --> 03:48:05,197
RETROVIRAL 1.

6117
03:48:05,197 --> 03:48:07,799
AGAIN WE USE AN AAV DELIVERY

6118
03:48:07,799 --> 03:48:14,539
SYSTEM AND IN RF3, AND WE HAVE

6119
03:48:14,539 --> 03:48:18,377
OUR IN VIVO ANALYSES.

6120
03:48:18,377 --> 03:48:19,711
SO I WANTED TO GIVE A LITTLE

6121
03:48:19,711 --> 03:48:20,879
ABOUT WE'RE A NEW COLLABORATORY

6122
03:48:20,879 --> 03:48:22,180
BUT THESE PAPERS WERE DIRECTLY

6123
03:48:22,180 --> 03:48:23,582
FUNDED OR PARTIALLY FUNDED BY

6124
03:48:23,582 --> 03:48:25,350
THE CRISPR FOR CURE

6125
03:48:25,350 --> 03:48:27,986
COLLABORATORY, SO AS CLEARLY

6126
03:48:27,986 --> 03:48:30,489
ALLUDED TO, THE PAPER LOOKING AT

6127
03:48:30,489 --> 03:48:33,458
CRISPR EDITING BETWEEN CCR5 AND

6128
03:48:33,458 --> 03:48:34,793
HIV, AS WELL AS WE DID ANOTHER

6129
03:48:34,793 --> 03:48:41,800
STUDY LOOKING AT THE CRISPR

6130
03:48:41,800 --> 03:48:44,970
EDITING OF PROTEIN COSMOGS AND

6131
03:48:44,970 --> 03:48:45,971
THEN SOME OTHER STUDIES YOU CAN

6132
03:48:45,971 --> 03:48:46,471
SEE AS WELL.

6133
03:48:46,471 --> 03:48:48,573
I JUST WANTED TO BRING UP OUR

6134
03:48:48,573 --> 03:48:50,409
CORPORATE PARTNER WHICH IS

6135
03:48:50,409 --> 03:48:51,109
EXCISION BIOTHERAPEUTICS.

6136
03:48:51,109 --> 03:48:56,715
WE DID A PAPER WITH THEM ABOUT

6137
03:48:56,715 --> 03:49:00,218
THE RECLINICAL SAFETY FOR SAB

6138
03:49:00,218 --> 03:49:01,353
NON-HUMAN PRIMATES AND THAT WAS

6139
03:49:01,353 --> 03:49:03,288
NOT FUNDED BY THE DELANEY.

6140
03:49:03,288 --> 03:49:04,957
AS ALLUDED TO, THEY HAVE

6141
03:49:04,957 --> 03:49:08,860
RECEIVED FDA APPROVAL FOR USING

6142
03:49:08,860 --> 03:49:14,466
CRISPR IN PEOPLE WITH HIV.

6143
03:49:14,466 --> 03:49:17,169
NOW I'M GOING TO INVITE BEN, ONE

6144
03:49:17,169 --> 03:49:21,139
OF OUR EARLY STAGE

6145
03:49:21,139 --> 03:49:22,240
INVESTIGATORS FROM THE LAB.

6146
03:49:22,240 --> 03:49:32,417
[APPLAUSE]

6147
03:49:45,397 --> 03:49:46,298
>> THANK YOU.

6148
03:49:46,298 --> 03:49:48,900
I'D LIKE TO GIVE A BRIEF

6149
03:49:48,900 --> 03:49:50,202
OVERVIEW, KEY QUESTION BEING

6150
03:49:50,202 --> 03:49:51,837
WHETHER OR NOT RNA AND DNA

6151
03:49:51,837 --> 03:49:55,140
METHODS FOR MEASURING HIV

6152
03:49:55,140 --> 03:49:58,310
RESERVOIRS CAN BE ADAPTED TO

6153
03:49:58,310 --> 03:50:00,979
SIV -- CAN BE EVALUATED IN AN

6154
03:50:00,979 --> 03:50:02,714
SIV INFECTED RHESUS MACAQUE

6155
03:50:02,714 --> 03:50:03,181
MODEL.

6156
03:50:03,181 --> 03:50:04,349
SOME KEY FINDINGS, WE AND OTHERS

6157
03:50:04,349 --> 03:50:06,718
HAVE BEEN SUCCESSFUL FOR

6158
03:50:06,718 --> 03:50:09,721
ADAPTING THESE MEASUREMENT

6159
03:50:09,721 --> 03:50:13,125
TECHNIQUES FOR HIV RESERVOIRS

6160
03:50:13,125 --> 03:50:13,892
ADAPTIVE FOR SIV.

6161
03:50:13,892 --> 03:50:15,627
THIS IS IMPORTANT BECAUSE DOING

6162
03:50:15,627 --> 03:50:16,962
RESERVOIR MEASUREMENTS OF SIV

6163
03:50:16,962 --> 03:50:18,897
WILL HELP EVALUATE POTENTIAL

6164
03:50:18,897 --> 03:50:19,865
ERADICATION STRATEGIES THAT WE

6165
03:50:19,865 --> 03:50:21,767
HOPE CAN EFFICIENTLY BE APPLIED

6166
03:50:21,767 --> 03:50:25,270
TO HIV.

6167
03:50:25,270 --> 03:50:26,471
WE'RE EXCITED ABOUT THIS BECAUSE

6168
03:50:26,471 --> 03:50:27,672
WE NOW BASE BACEICALLY HAVE MANY

6169
03:50:27,672 --> 03:50:29,307
OF THE TOOLS WE WOULD NEED TO

6170
03:50:29,307 --> 03:50:30,242
SHOW SIGNIFICANT REDUCTION IN

6171
03:50:30,242 --> 03:50:32,677
HIV RESERVOIRS ON A PATH TOWARDS

6172
03:50:32,677 --> 03:50:33,745
EVENTUALLY GETTING SOMEONE OFF

6173
03:50:33,745 --> 03:50:35,814
OF THERAPY OR AT LEAST HAVING

6174
03:50:35,814 --> 03:50:39,217
THERAPY INTERRUPTION, BUT AN TAI

6175
03:50:39,217 --> 03:50:40,452
WOULD NOT BE NEEDED BECAUSE

6176
03:50:40,452 --> 03:50:41,520
THESE TECHNIQUES ARE SO

6177
03:50:41,520 --> 03:50:43,522
SENSITIVE TO SEE WHETHER OR NOT

6178
03:50:43,522 --> 03:50:44,923
WE HAVE A REDUCTION IN THE

6179
03:50:44,923 --> 03:50:45,891
RESERVOIR AND IF IT'S SAFE TO

6180
03:50:45,891 --> 03:50:48,293
CONTINUE.

6181
03:50:48,293 --> 03:50:49,661
SO TODAY I'LL BE DESCRIBING OUR

6182
03:50:49,661 --> 03:50:51,763
METHOD FOR DETECTING HIV

6183
03:50:51,763 --> 03:50:53,698
PROVIRUSES USING A DIGITAL PCR,

6184
03:50:53,698 --> 03:50:55,000
AND THIS IS A METHOD WE

6185
03:50:55,000 --> 03:50:56,334
DEVELOPED PRIOR TO THE

6186
03:50:56,334 --> 03:50:57,903
PUBLICATION OF THE MORE WIDELY

6187
03:50:57,903 --> 03:51:00,005
ADOPTED IPDA.

6188
03:51:00,005 --> 03:51:02,407
IT'S USING A SLIGHTLY DIFFERENT

6189
03:51:02,407 --> 03:51:03,542
APPROACH BUT YIELDS VERY SIMILAR

6190
03:51:03,542 --> 03:51:05,811
RESULTS.

6191
03:51:05,811 --> 03:51:08,880
HERE ARE THE BINDING SITES FOR

6192
03:51:08,880 --> 03:51:13,985
OUR PRIMER PROBE SETS IN AFN

6193
03:51:13,985 --> 03:51:15,420
ASSAY WE CALL THE POTENTIALLY

6194
03:51:15,420 --> 03:51:19,357
INTACT PROVIRAL LOAD ASSAY OR

6195
03:51:19,357 --> 03:51:20,058
PIPL FOR SHORT.

6196
03:51:20,058 --> 03:51:21,593
YOU CAN SEE IN COMPARISON WITH

6197
03:51:21,593 --> 03:51:22,461
THE IPDA.

6198
03:51:22,461 --> 03:51:23,829
SO WE WERE ABLE TO USE THIS

6199
03:51:23,829 --> 03:51:27,265
ASSAY TO SHOW IN VITRO SOME

6200
03:51:27,265 --> 03:51:29,201
REDUCTIONS OF HIV RESERVOIRS

6201
03:51:29,201 --> 03:51:31,169
AFTER TREATMENT WITH CYTOTOXIC

6202
03:51:31,169 --> 03:51:32,671
NK CELLS THAT WERE EXPANDED IN

6203
03:51:32,671 --> 03:51:35,640
OUR LABORATORY AND WORKED WITH

6204
03:51:35,640 --> 03:51:38,310
MARY ANN AND THAT'S GOING TO BE

6205
03:51:38,310 --> 03:51:42,747
PUBLISHED LATER THIS YEAR.

6206
03:51:42,747 --> 03:51:45,517
SO ALL HIV CELLS AS YOU KNOW

6207
03:51:45,517 --> 03:51:48,386
CONTAIN A COPY OF THE HIV GENOME

6208
03:51:48,386 --> 03:51:49,754
SHOWN HERE INTEGRATED INTO THEIR

6209
03:51:49,754 --> 03:51:51,256
DNA BUT MOST PROVIRUSES IN

6210
03:51:51,256 --> 03:51:53,125
PEOPLE LIVING WITH HIV ARE

6211
03:51:53,125 --> 03:51:54,459
DEFECTIVE DUE TO LARGE

6212
03:51:54,459 --> 03:51:55,560
DELUSIONS, SO AN IMPORTANT PART

6213
03:51:55,560 --> 03:51:57,896
OF FINDING AN HIV CURE IS TO

6214
03:51:57,896 --> 03:51:59,297
DETERMINE HOW MANY OF THESE

6215
03:51:59,297 --> 03:52:01,600
PROVIRUSES ARE ACTUALLY INTACT

6216
03:52:01,600 --> 03:52:02,934
SINCE THIS IS AT LEAST ONE

6217
03:52:02,934 --> 03:52:05,070
REQUIREMENT TO MAKING A

6218
03:52:05,070 --> 03:52:06,071
REPLICATION COMPETENT VIRUS THAT

6219
03:52:06,071 --> 03:52:08,073
CAN SPREAD TO OTHER CELLS AND

6220
03:52:08,073 --> 03:52:10,609
INCREASE THE VIRAL RESERVOIR.

6221
03:52:10,609 --> 03:52:14,379
SO IN OUR ASSAY, THE DNA IS

6222
03:52:14,379 --> 03:52:17,382
EXTRACTED FROM CD4 T-CELLS AND

6223
03:52:17,382 --> 03:52:19,751
THEN MIXED WITH PCR REAGENTS AND

6224
03:52:19,751 --> 03:52:21,286
PRIMERS AND PROBE FOR GAG AND

6225
03:52:21,286 --> 03:52:22,687
ENVELOPE AND THESE ARE SPREAD ON

6226
03:52:22,687 --> 03:52:27,959
TO A MICRO CHIP IN SOLUTION WITH

6227
03:52:27,959 --> 03:52:29,094
ABOUT 20,000 WELLS PER CHIP AND

6228
03:52:29,094 --> 03:52:30,896
THIS IS DONE WITHOUT MAKING ANY

6229
03:52:30,896 --> 03:52:33,532
OIL-BASED DROP LETS.

6230
03:52:33,532 --> 03:52:35,167
AFTER THERMAL CYCLING AND

6231
03:52:35,167 --> 03:52:36,368
SCANNING FOR FLUORESCENCE, ONE

6232
03:52:36,368 --> 03:52:38,136
CAN SEE PROVIRUS IS DETECTED

6233
03:52:38,136 --> 03:52:39,905
ONLY WITH GAG OR ENVELOPE

6234
03:52:39,905 --> 03:52:41,206
PRIMERS, AND SO THESE SINGLE

6235
03:52:41,206 --> 03:52:43,575
POSITIVES ARE CONSIDERED

6236
03:52:43,575 --> 03:52:45,844
DEFECTIVE, COMPARED TO THE MORE

6237
03:52:45,844 --> 03:52:47,546
RARE DOUBLE POSITIVES RECOGNIZED

6238
03:52:47,546 --> 03:52:49,247
BY BOTH SETS OF PRIMERS, WHICH

6239
03:52:49,247 --> 03:52:50,415
WE WOULD CONSIDER TO BE

6240
03:52:50,415 --> 03:52:52,784
POTENTIALLY INTACT.

6241
03:52:52,784 --> 03:52:54,286
AGAIN THIS IS PROBABLY BASED ON

6242
03:52:54,286 --> 03:52:56,288
RESULTS PUBLISHED USING THE IPDA

6243
03:52:56,288 --> 03:52:59,791
METHOD.

6244
03:52:59,791 --> 03:53:01,326
SO SHOWN HERE ARE SOME IMPORTANT

6245
03:53:01,326 --> 03:53:04,329
CONTROLS FOR THIS ASSAY, WHICH

6246
03:53:04,329 --> 03:53:06,798
WOULD BE TRUE OF ANY IPDA.

6247
03:53:06,798 --> 03:53:08,767
SO THE DNA FROM HIV NEGATIVE

6248
03:53:08,767 --> 03:53:10,068
CELLS HELP ESTABLISH THE

6249
03:53:10,068 --> 03:53:10,969
BACKGROUND LEVELS OF

6250
03:53:10,969 --> 03:53:12,470
FLUORESCENCE THAT WE CAN EXCLUDE

6251
03:53:12,470 --> 03:53:14,439
AND WHEN THIS DNA IS MIXED WITH

6252
03:53:14,439 --> 03:53:18,143
A MOLECULAR CLONE OF HIV, THIS

6253
03:53:18,143 --> 03:53:20,111
REPRESENTS A 100% INTACT

6254
03:53:20,111 --> 03:53:22,214
PROVIRUS AND IN THIS CON TECH,

6255
03:53:22,214 --> 03:53:25,750
WITHIN ACCESS OF HIV NEGATIVE

6256
03:53:25,750 --> 03:53:26,918
DNA THERE'S NO FALSE DETECTION

6257
03:53:26,918 --> 03:53:28,453
OF DEFECTIVE SINGLE POSITIVE

6258
03:53:28,453 --> 03:53:30,422
PROVIRUSES DUE TO ANY PCR

6259
03:53:30,422 --> 03:53:32,691
INHIBITION OR ERRORS, AND SO ALL

6260
03:53:32,691 --> 03:53:35,327
THAT WE SEE ARE DETECTED AS

6261
03:53:35,327 --> 03:53:36,261
INTACT WITH THIS APPROACH.

6262
03:53:36,261 --> 03:53:38,763
ON THE RIGHT IS AN EXAMPLE OF

6263
03:53:38,763 --> 03:53:41,600
MEMORY CD4 T-CELLS DNA FROM A

6264
03:53:41,600 --> 03:53:43,501
PERSON WITH HIV ON ART.

6265
03:53:43,501 --> 03:53:44,970
THIS ILLUSTRATES THE ABUNDANCE

6266
03:53:44,970 --> 03:53:47,572
OF DEFECTIVE PROVIRUSES DETECTED

6267
03:53:47,572 --> 03:53:49,207
WITH OUR ASSAY VERY SIMILAR TO

6268
03:53:49,207 --> 03:53:51,276
THE IPDA IN THESE SINGLE

6269
03:53:51,276 --> 03:53:53,712
POSITIVES AND ONLY A RARE

6270
03:53:53,712 --> 03:53:56,648
PROPORTION IS ACTUALLY A DOUBLE

6271
03:53:56,648 --> 03:53:57,849
POSITIVE THAT WOULD BE

6272
03:53:57,849 --> 03:53:58,750
CONSIDERED POTENTIALLY INTACT,

6273
03:53:58,750 --> 03:54:02,921
IN THIS CASE ONLY 4%.

6274
03:54:02,921 --> 03:54:04,990
SO BASED ON MY EXPERIENCE WITH

6275
03:54:04,990 --> 03:54:06,725
DOING THESE KINDS OF ASSAYS, I

6276
03:54:06,725 --> 03:54:10,328
WAS RECRUITED BY THE CRISPR FOR

6277
03:54:10,328 --> 03:54:13,598
CURE TO GET SOME OF THE

6278
03:54:13,598 --> 03:54:16,668
PUBLISHED SIV IPDAs UP AND

6279
03:54:16,668 --> 03:54:19,304
RUNNING WITH OUR EQUIPMENT SO WE

6280
03:54:19,304 --> 03:54:22,107
COULD EVALUATE IN RHESUS

6281
03:54:22,107 --> 03:54:22,474
MACAQUES.

6282
03:54:22,474 --> 03:54:25,577
SO THE LOCATIONS AND PRIMERS OF

6283
03:54:25,577 --> 03:54:29,581
THE PROBES USED IN THE SIV ARE

6284
03:54:29,581 --> 03:54:31,349
SHOWN HERE IN COMPARISON WITH

6285
03:54:31,349 --> 03:54:33,818
THE HIV, AND AGAIN THIS WAS

6286
03:54:33,818 --> 03:54:37,889
DEVELOPED FROM BOB SILICANO'S

6287
03:54:37,889 --> 03:54:38,957
LAB, TO SEE WHERE THE DELETIONS

6288
03:54:38,957 --> 03:54:41,793
TEND TO OCCUR, AND SO THEY

6289
03:54:41,793 --> 03:54:42,794
DETERMINED THAT POLE, AN

6290
03:54:42,794 --> 03:54:45,230
ENVELOPE WHERE THE BEST TARGETS

6291
03:54:45,230 --> 03:54:47,932
TO PROBE FOR.

6292
03:54:47,932 --> 03:54:49,701
AGAIN WE'RE GOING TO ADAPT THIS

6293
03:54:49,701 --> 03:54:52,637
APPROACH USING OUR MICRO

6294
03:54:52,637 --> 03:54:57,909
CHIP-BASED DIGITAL PCR.

6295
03:54:57,909 --> 03:55:00,078
I HIT A BUTTON.

6296
03:55:00,078 --> 03:55:05,216
HOW DO I GET BACK TO -- THIS IS

6297
03:55:05,216 --> 03:55:15,694
NOT -- SO HERE'S HOW THE SIV

6298
03:56:22,460 --> 03:56:23,294
IPDA IS LOOKING.

6299
03:56:23,294 --> 03:56:24,195
WITH OUR EQUIPMENT, AGAIN, THIS

6300
03:56:24,195 --> 03:56:26,264
IS NOT BASED ON A DIGITAL

6301
03:56:26,264 --> 03:56:27,465
DROPLET BUT IT'S A SIMILAR IDEA.

6302
03:56:27,465 --> 03:56:29,434
ATION YOU CAN SEE, THE CONTROL

6303
03:56:29,434 --> 03:56:31,136
WITH SIV NEGATIVE CELLS HAS VERY

6304
03:56:31,136 --> 03:56:32,670
LITTLE BACKGROUND, COMES OUT

6305
03:56:32,670 --> 03:56:34,239
VERY CLEAN, AND SO ON THE RIGHT,

6306
03:56:34,239 --> 03:56:39,077
I TESTED CD4 T-CELL DNA FROM

6307
03:56:39,077 --> 03:56:40,645
SHIF INFECTED RHESUS MACAQUE AND

6308
03:56:40,645 --> 03:56:43,548
THIS IS CLEARLY DETECTING

6309
03:56:43,548 --> 03:56:45,083
DEFECTIVE PROVIRUSES IN BLUE AND

6310
03:56:45,083 --> 03:56:46,584
RED DOTS COMPARED TO THE

6311
03:56:46,584 --> 03:56:48,386
POTENTIALLY INTACT PROVIRUSES

6312
03:56:48,386 --> 03:56:51,756
SHOWN IN GREEN.

6313
03:56:51,756 --> 03:56:54,692
SO SWITCHING GEARS NOW, WE CAN

6314
03:56:54,692 --> 03:56:58,196
ALSO DETECT SPLICED HIV MRNA AS

6315
03:56:58,196 --> 03:56:59,731
A WAY TO QUANTIFY POTENTIAL

6316
03:56:59,731 --> 03:57:01,966
RESERVOIR, SO IN RESPONSE TO HIV

6317
03:57:01,966 --> 03:57:03,635
AT THAT TIME, IT'S TRANSCRIBED

6318
03:57:03,635 --> 03:57:10,775
AND SPLICED, REHE MOV REMOVING E

6319
03:57:10,775 --> 03:57:13,178
SECTION ON THE LEFT OR DOUBLY

6320
03:57:13,178 --> 03:57:14,145
SPLICED REMOVING THIS REGION ON

6321
03:57:14,145 --> 03:57:16,514
THE RIGHT, OR UNSPLICED, AND ALL

6322
03:57:16,514 --> 03:57:18,783
THE SPLICED RNAs USE A MAJOR

6323
03:57:18,783 --> 03:57:20,885
SUPPLIES DONOR SITE D1 AND THOSE

6324
03:57:20,885 --> 03:57:24,489
THAT DO NOT REMAIN UNSPLICED.

6325
03:57:24,489 --> 03:57:27,425
SO THE CELLS THAT CAN PRODUCE

6326
03:57:27,425 --> 03:57:29,494
SPLICED HV RNAs ARE NOT

6327
03:57:29,494 --> 03:57:30,562
ENTIRELY DEFECTIVE BECAUSE HIV

6328
03:57:30,562 --> 03:57:32,163
AT THAT TIME IS PRESENT,

6329
03:57:32,163 --> 03:57:33,231
SUPPLIES ACCEPTOR SITES ARE

6330
03:57:33,231 --> 03:57:34,098
PRESENT, SO WE CONSIDER THAT

6331
03:57:34,098 --> 03:57:35,733
THESE CELLS ARE MORE LIKELY TO

6332
03:57:35,733 --> 03:57:38,236
EXPRESS HIV PROTEINS, POSSIBLY

6333
03:57:38,236 --> 03:57:40,104
RELEASE HIV, AND CONTRIBUTE TO

6334
03:57:40,104 --> 03:57:43,274
CHRONIC IMMUNE CELL EXHAUSTION.

6335
03:57:43,274 --> 03:57:45,376
HOWEVER, NOT ALL OF THESE CELLS

6336
03:57:45,376 --> 03:57:46,778
NECESSARILY HAVE INTACT

6337
03:57:46,778 --> 03:57:47,579
PROVIRUSES THAT COULD INCREASE

6338
03:57:47,579 --> 03:57:50,949
THE SIZE OF THE RESERVOIR, AND

6339
03:57:50,949 --> 03:57:53,485
LATENTLY INFECTED CELLS ALSO

6340
03:57:53,485 --> 03:57:54,686
WOULD NOT BE ABLE TO EXPRESS

6341
03:57:54,686 --> 03:57:56,321
THESE RNAs EVEN IF THE

6342
03:57:56,321 --> 03:57:57,989
PROVIRUSES WE DETECT ARE INTACT.

6343
03:57:57,989 --> 03:58:01,659
SO IT'S BEEN SHOWN -- THIS GOT A

6344
03:58:01,659 --> 03:58:03,127
LITTLE MESSED UP BUT IT'S FINE.

6345
03:58:03,127 --> 03:58:04,395
IT'S BEEN SHOWN THAT VAST

6346
03:58:04,395 --> 03:58:06,364
MAJORITY OF SINGLY AND DOUBLY

6347
03:58:06,364 --> 03:58:08,500
SPLICED RNAs SPLICED FROM THIS

6348
03:58:08,500 --> 03:58:10,735
DONOR 1 SITE TO EITHER ACCEPTOR

6349
03:58:10,735 --> 03:58:13,071
4 OR 5, ESPECIALLY WITH A VERY

6350
03:58:13,071 --> 03:58:14,939
HIGH PREFERENCE FOR ACCEPTOR 5,

6351
03:58:14,939 --> 03:58:15,907
1 THING THAT I NOTICED IS THAT

6352
03:58:15,907 --> 03:58:18,943
ALL OF THESE RNAs WHICH ENCODE

6353
03:58:18,943 --> 03:58:22,247
FOR ENVELOPE, REV AND NEF, THEY

6354
03:58:22,247 --> 03:58:26,417
ALL SHARE THIS COMMON SEQUENCE R

6355
03:58:26,417 --> 03:58:26,818
4 SITE.

6356
03:58:26,818 --> 03:58:28,119
SO WHAT THIS MEANS IS THAT BY

6357
03:58:28,119 --> 03:58:30,355
PRIMING ON EITHER SIDE OF THIS

6358
03:58:30,355 --> 03:58:32,190
JUNCTION, BETWEEN DONOR 1 AND

6359
03:58:32,190 --> 03:58:33,525
ACCEPTOR 5, IT POSSIBLE TO

6360
03:58:33,525 --> 03:58:35,360
DETECT ALL OF THESE RNAs, AT

6361
03:58:35,360 --> 03:58:40,265
LEAST THEORETICALLY BY RTPCR, SO

6362
03:58:40,265 --> 03:58:42,033
PREVIOUSLY QPCR METHODS THAT

6363
03:58:42,033 --> 03:58:43,902
RELIED ON A MORE TWO-STEP

6364
03:58:43,902 --> 03:58:44,969
APPROACH, ONE ROUND FOLLOWED BY

6365
03:58:44,969 --> 03:58:47,272
A NESTED QPCR, BUT WITH MY

6366
03:58:47,272 --> 03:58:48,406
PROTOCOL AND THE PRIMERS THAT

6367
03:58:48,406 --> 03:58:50,575
I'VE MADE, IT'S ACTUALLY

6368
03:58:50,575 --> 03:58:51,476
POSSIBLE -- IT'S ACTUALLY

6369
03:58:51,476 --> 03:58:53,278
SENSITIVE ENOUGH TO DETECT THESE

6370
03:58:53,278 --> 03:58:57,015
RNAs BY A SI SINGLE ONE STEP

6371
03:58:57,015 --> 03:59:00,285
DIGITAL PCR SO THIS GIVES A

6372
03:59:00,285 --> 03:59:01,052
SIGNIFICANT ADVANTAGE BECAUSE

6373
03:59:01,052 --> 03:59:02,487
WITH DIGITAL PCR, YOU CAN

6374
03:59:02,487 --> 03:59:04,756
DIRECTLY COUNT THE RNA MOLECULES

6375
03:59:04,756 --> 03:59:07,392
THAT ARE SPREAD ON TO THE PCR

6376
03:59:07,392 --> 03:59:08,726
MICRO CHIP WITHOUT THE NEED FOR

6377
03:59:08,726 --> 03:59:10,562
STANDARD CURVE OR ANY REFERENCE.

6378
03:59:10,562 --> 03:59:12,764
SO THIS IS A POWERFUL TOOL.

6379
03:59:12,764 --> 03:59:17,502
IT'SIT'S VERY HIGHLY SPECIFIC TO

6380
03:59:17,502 --> 03:59:18,636
DETECTION OF RNA WITH VERY

6381
03:59:18,636 --> 03:59:20,038
LITTLE BACKGROUND IN UNAFFECTED

6382
03:59:20,038 --> 03:59:21,506
CELLS AND IT'S HIGHLY

6383
03:59:21,506 --> 03:59:22,307
QUANTITATIVE, WHICH I'M ABLE TO

6384
03:59:22,307 --> 03:59:24,375
SHOW WITH A SERIAL DELUSION OF A

6385
03:59:24,375 --> 03:59:26,210
KNOWN NUMBER OF HIV-POSITIVE

6386
03:59:26,210 --> 03:59:27,645
CELLS DELIVERED WITH HIV

6387
03:59:27,645 --> 03:59:29,581
NEGATIVE CELLS IN THIS RANGE OF

6388
03:59:29,581 --> 03:59:31,683
ABOUT 128 TO 512 CELLS PER

6389
03:59:31,683 --> 03:59:33,084
MILLION.

6390
03:59:33,084 --> 03:59:35,987
AND AGAIN THIS IS QUANTITATIVE,

6391
03:59:35,987 --> 03:59:37,288
VERY LINEAR RELATIONSHIP, AND

6392
03:59:37,288 --> 03:59:38,990
THE ASSAY IS SENSITIVE ENOUGH TO

6393
03:59:38,990 --> 03:59:41,726
DETECT INDUCIBLE HV RNA IN

6394
03:59:41,726 --> 03:59:43,828
PRIMARY CELLS, SO CD4 T-CELLS

6395
03:59:43,828 --> 03:59:45,430
FROM A PERSON LIVING WITH HIV,

6396
03:59:45,430 --> 03:59:47,865
AND THAT WE HAVE IN VITRO

6397
03:59:47,865 --> 03:59:49,200
STIMULATED OVERNIGHT AND SHOW

6398
03:59:49,200 --> 03:59:52,270
THE UPREGULATION OF HIV RNA.

6399
03:59:52,270 --> 03:59:54,405
WE CAN LITERALLY COUNT THESE

6400
03:59:54,405 --> 03:59:57,041
RNAs IN THE UNIT BEING THE

6401
03:59:57,041 --> 03:59:58,543
NUMBER OF RNA MOLECULES PER

6402
03:59:58,543 --> 03:59:59,777
MICROGRAM OF RNA.

6403
03:59:59,777 --> 04:00:05,483
TOTAL RNA.

6404
04:00:05,483 --> 04:00:08,653
SO I ALSO MODIFY THIS ASSAY TO

6405
04:00:08,653 --> 04:00:10,054
DETECT SIV RESERVOIRS IN RNA

6406
04:00:10,054 --> 04:00:14,158
FROM CD4 T-CELLS, INFECTED

6407
04:00:14,158 --> 04:00:16,094
RHESUS MACAQUES HERE SHOWING A

6408
04:00:16,094 --> 04:00:17,795
SIMILAR PRIMING STRATEGY, AND SO

6409
04:00:17,795 --> 04:00:20,765
HERE IS THE DATA THAT I GET FROM

6410
04:00:20,765 --> 04:00:24,268
THIS ASSAY, AGAIN THERE'S

6411
04:00:24,268 --> 04:00:27,038
NEGATIVE CELL RNA PUT INTO THE

6412
04:00:27,038 --> 04:00:28,439
ASSAY SO WE CAN DEFINE THE

6413
04:00:28,439 --> 04:00:30,842
BACKGROUND LEVEL OF FLUORESCENCE

6414
04:00:30,842 --> 04:00:32,610
TO FIND A THRESHOLD AND WITH

6415
04:00:32,610 --> 04:00:34,612
ACUTELY AFFECTED CELLS WE CAN

6416
04:00:34,612 --> 04:00:36,180
SHOW A HE HAVE HIGH LEVEL OF RNA

6417
04:00:36,180 --> 04:00:37,782
DETECTED AND ALSO ILLUSTRATING

6418
04:00:37,782 --> 04:00:38,716
THE DYNAMIC RANGE OF THIS ASSAY,

6419
04:00:38,716 --> 04:00:40,451
SO OVER 200,000 RNA MOLECULES

6420
04:00:40,451 --> 04:00:42,253
CAN BE DETECTED PER MICROGRAM

6421
04:00:42,253 --> 04:00:43,821
WITHOUT SATURATION.

6422
04:00:43,821 --> 04:00:46,824
AND THEN MORE IMPORTANTLY, USING

6423
04:00:46,824 --> 04:00:48,826
CD4 T-CELLS FROM AN SIV INFECTED

6424
04:00:48,826 --> 04:00:50,995
RHESUS MACAQUE WE'RE ABLE TO

6425
04:00:50,995 --> 04:00:52,964
DETECT EVEN IN AN UNSTIMULATED

6426
04:00:52,964 --> 04:00:54,565
STATE SIV MRNAs THAT ARE

6427
04:00:54,565 --> 04:00:55,867
SPLICED, AND THEN WHEN WE TREAT

6428
04:00:55,867 --> 04:00:58,603
THESE CELLS OVERNIGHT WITH A --

6429
04:00:58,603 --> 04:00:59,737
STIMULUS, WE CAN ALSO SAMPLE

6430
04:00:59,737 --> 04:01:02,006
THOSE AND SEE INDUCTION OF SIV

6431
04:01:02,006 --> 04:01:03,675
RNA AND SHOW THAT THERE WAS

6432
04:01:03,675 --> 04:01:07,478
LATENCY IN THIS SYSTEM.

6433
04:01:07,478 --> 04:01:10,314
SO IN CONCLUSION, I THINK I'M

6434
04:01:10,314 --> 04:01:12,316
ABLE TO CONVINCE YOU THAT WE'RE

6435
04:01:12,316 --> 04:01:16,120
ABLE TO DETECT -- RNAs

6436
04:01:16,120 --> 04:01:18,256
DIRECTLY BY ONE STEP

6437
04:01:18,256 --> 04:01:19,757
ADDITIONAL -- PCR.

6438
04:01:19,757 --> 04:01:22,326
THIS ASSAY IS HIGHLY SPECIFIC,

6439
04:01:22,326 --> 04:01:22,960
QUANTITATIVE, SENSITIVE ENOUGH

6440
04:01:22,960 --> 04:01:24,429
THAT YOU CAN DETECT RESERVOIRS

6441
04:01:24,429 --> 04:01:25,763
IN PRIMARY SAMPLES AND ALSO I

6442
04:01:25,763 --> 04:01:27,932
CAN SHOW SIV LATENCY IN RHESUS

6443
04:01:27,932 --> 04:01:28,266
MACAQUES.

6444
04:01:28,266 --> 04:01:29,333
SO OUR PLAN IS TO APPLY THIS

6445
04:01:29,333 --> 04:01:32,236
KIND OF APPROACH TO SAMPLES FROM

6446
04:01:32,236 --> 04:01:34,338
SIV INFECTED RHESUS MACAQUES ON

6447
04:01:34,338 --> 04:01:36,641
ART WITH OR WITHOUT A CRISPR

6448
04:01:36,641 --> 04:01:38,543
MEDIATED ERADICATION STRATEGY.

6449
04:01:38,543 --> 04:01:41,145
AND JUST LIKE TO GIVE THANKS TO

6450
04:01:41,145 --> 04:01:43,347
BRANDON KEEL WHO'S MADE A

6451
04:01:43,347 --> 04:01:44,716
BARCODED VERSION OF SIV THAT

6452
04:01:44,716 --> 04:01:45,917
YOU'LL HEAR MORE ABOUT LATER,

6453
04:01:45,917 --> 04:01:47,618
AND THE SAMPLES WE GET FROM

6454
04:01:47,618 --> 04:01:49,887
RHESUS MACAQUES PROVIDED BY

6455
04:01:49,887 --> 04:01:54,192
TRISHA BURDOW.

6456
04:01:54,192 --> 04:01:57,028
THANKS TO JONATHAN KARN FOR

6457
04:01:57,028 --> 04:01:58,262
MENTORSHIP AND THANKS FOR THE

6458
04:01:58,262 --> 04:02:01,933
FUNDING FROM THE CRIP  CRISPR FE

6459
04:02:01,933 --> 04:02:03,034
AND OUR LOCAL CFAR.

6460
04:02:03,034 --> 04:02:03,501
THANK YOU VERY MUCH.

6461
04:02:03,501 --> 04:02:09,841
[APPLAUSE]

6462
04:02:09,841 --> 04:02:11,109
>> NEXT I'M GOING TO TALK
ABOUT

6463
04:02:11,109 --> 04:02:12,543
SOME OF OUR WORK WITH RF2.

6464
04:02:12,543 --> 04:02:15,980
SO I WANT TO SAY THAT RCHT

6465
04:02:15,980 --> 04:02:17,115
F2 HAS A NUMBER OF DIFFERENT

6466
04:02:17,115 --> 04:02:18,182
PROJECTS AND I'M ONLY GOING TO

6467
04:02:18,182 --> 04:02:19,217
BE TALKING ABOUT ONE OF THE

6468
04:02:19,217 --> 04:02:22,019
OBJECTIVES IN THIS PROJECT.

6469
04:02:22,019 --> 04:02:23,254
THERE'S A LOT OF PEOPLE THAT ARE

6470
04:02:23,254 --> 04:02:25,690
INVOLVED IN THESE STUDIES.

6471
04:02:25,690 --> 04:02:27,291
SPECIFICALLY SOME OF THE PIs

6472
04:02:27,291 --> 04:02:30,128
AT TEMPLE OR MYSELF,

6473
04:02:30,128 --> 04:02:31,896
DR. KAMINSKI, DR. SHANE IS

6474
04:02:31,896 --> 04:02:34,499
INVOLVED IN THE MR. G STUDIES,

6475
04:02:34,499 --> 04:02:36,901
DR. KARN AND HIS GROUP AND THEN

6476
04:02:36,901 --> 04:02:41,072
WE WORK WITH EXCISION

6477
04:02:41,072 --> 04:02:43,174
BIOTHERAPEUTICS AND DR. JERRY

6478
04:02:43,174 --> 04:02:43,741
ZACK.

6479
04:02:43,741 --> 04:02:45,209
I WON'T BE SHARING ANY OF THE

6480
04:02:45,209 --> 04:02:49,413
MONKEY STUDIES BUT THOSE ARE

6481
04:02:49,413 --> 04:02:50,815
DONE WITH MARK -- SO HERE'S MY

6482
04:02:50,815 --> 04:02:51,949
PLAIN LANGUAGE SUMMARY.

6483
04:02:51,949 --> 04:02:53,551
WHAT I'M GOING TO BE TALKING

6484
04:02:53,551 --> 04:02:56,287
ABOUT IS CAN WE USE GENE EDITING

6485
04:02:56,287 --> 04:02:58,723
TO REMOVE THE HIV RECEPTOR

6486
04:02:58,723 --> 04:03:01,726
CCR5 TO STOP HIV FROM ENTERING

6487
04:03:01,726 --> 04:03:02,426
CELLS.

6488
04:03:02,426 --> 04:03:04,762
SO KEY FINDINGS WERE CRIP PER

6489
04:03:04,762 --> 04:03:06,164
TECHNOLOGIES HAVE SHOWN

6490
04:03:06,164 --> 04:03:07,632
PROMISING RESULTS IN CELL

6491
04:03:07,632 --> 04:03:10,268
CULTURE, BLOOD AND MOUSE MODEL.

6492
04:03:10,268 --> 04:03:11,536
AND WHY IS THIS IMPORTANT?

6493
04:03:11,536 --> 04:03:13,237
SO PAST STUDIES HAVE SHOWN THAT

6494
04:03:13,237 --> 04:03:14,972
WHEN WE TRANSFER BONE MARROW

6495
04:03:14,972 --> 04:03:16,674
CELLS MISSING A PART OF THE CC

6496
04:03:16,674 --> 04:03:21,245
RMPLECCR5, WHICH WE CALL DELTA ,

6497
04:03:21,245 --> 04:03:22,547
IT CAN LEAD TO A CURE.

6498
04:03:22,547 --> 04:03:23,981
WHY SHOULD WE BE EXCITED ABOUT

6499
04:03:23,981 --> 04:03:24,315
THIS?

6500
04:03:24,315 --> 04:03:25,716
THIS IS NOVEL RESEARCH WITH THE

6501
04:03:25,716 --> 04:03:28,119
GOAL OF REMOVING CCR5 TO BLOCK

6502
04:03:28,119 --> 04:03:28,820
HIV INFECTION.

6503
04:03:28,820 --> 04:03:30,555
AND A LOT OF PEOPLE HAVE TALKED

6504
04:03:30,555 --> 04:03:35,126
ABOUT DOING THIS HIV BLOCKING

6505
04:03:35,126 --> 04:03:36,661
CCR5 IN THE PAST COUPLE DAYS,

6506
04:03:36,661 --> 04:03:39,664
BUT OUR STRATEGY IS REALLY TO DO

6507
04:03:39,664 --> 04:03:43,801
AN IN VIVO GENE EDITING PROCESS.

6508
04:03:43,801 --> 04:03:44,869
SO AGAIN THE OBJECTIVE FOR THIS

6509
04:03:44,869 --> 04:03:49,140
IS TO KNOCK OUT CCR5 BY USING

6510
04:03:49,140 --> 04:03:50,842
CRISPR/CAS 9 GENE EDITING AND

6511
04:03:50,842 --> 04:03:54,912
THIS WILL LIMIT BORROW SPREAD

6512
04:03:54,912 --> 04:03:56,447
AND INFECTION AND POTENTIALLY

6513
04:03:56,447 --> 04:03:57,481
PROVIDE HELPER CELL FUNCTION.

6514
04:03:57,481 --> 04:04:00,718
SO REALLY OUR STRATEGY IS TO

6515
04:04:00,718 --> 04:04:05,656
PRODUCE TWO GUIDE RNAs, WE USE

6516
04:04:05,656 --> 04:04:07,792
TWO GUIDE RNAs TO COMPLETELY

6517
04:04:07,792 --> 04:04:10,328
REMOVE A SECTION OF THE CCR5 AND

6518
04:04:10,328 --> 04:04:15,566
RENDER IT INCAPABLE OF HAVING

6519
04:04:15,566 --> 04:04:18,102
HIV INFECT CELLS.

6520
04:04:18,102 --> 04:04:19,503
SO I'M NOT GOING TO TALK A LOT

6521
04:04:19,503 --> 04:04:20,838
ABOUT OUR PAST STUDY, BUT I DO

6522
04:04:20,838 --> 04:04:25,877
WANT TO MAKE A NOTE OF OUR PAPER

6523
04:04:25,877 --> 04:04:29,947
DONE IN COLLABORATION WITH

6524
04:04:29,947 --> 04:04:32,516
DR. GENDELMAN AND DR. CALILI.

6525
04:04:32,516 --> 04:04:33,851
I WAS AN AUTHOR ON THERE AS

6526
04:04:33,851 --> 04:04:35,286
WELL, BUT IT'S A BIG GROUP OF

6527
04:04:35,286 --> 04:04:37,989
PEOPLE LOOKING TO LOOK AT CRISPR

6528
04:04:37,989 --> 04:04:40,424
GENE EDITING OF CCR5, AND WE DID

6529
04:04:40,424 --> 04:04:42,360
THIS IN COMBINATION WITH A --

6530
04:04:42,360 --> 04:04:46,097
USING HIV CRISPR.

6531
04:04:46,097 --> 04:04:48,165
SO AGAIN WE SHOWED AT THE BOTTOM

6532
04:04:48,165 --> 04:04:50,067
A KIND OF OVERALL VIEW OF THE

6533
04:04:50,067 --> 04:04:50,268
STUDY.

6534
04:04:50,268 --> 04:04:55,273
SO THE MICE WERE ON ART, AND SO

6535
04:04:55,273 --> 04:04:58,009
RED OR -- THIS KIND OF GREY OR

6536
04:04:58,009 --> 04:04:59,911
ORANGE COLOR IS WHEN WE HAD

6537
04:04:59,911 --> 04:05:01,112
REBOUND AND WHITE IS WHEN WE DID

6538
04:05:01,112 --> 04:05:02,046
NOT HAVE REBOUND.

6539
04:05:02,046 --> 04:05:05,383
SO AS YOU CAN SEE, AS WE USED A

6540
04:05:05,383 --> 04:05:09,053
SINGLE CRISPR CCR5 OR IF WE USED

6541
04:05:09,053 --> 04:05:11,155
HIV CRISPR, WE HAD SOME ANIMALS

6542
04:05:11,155 --> 04:05:13,591
THAT DID NOT REBOUND AFTER AN

6543
04:05:13,591 --> 04:05:16,394
ATI, BUT WHEN WE USED BOTH THE

6544
04:05:16,394 --> 04:05:21,198
ART AND THE TWO CRISPRS, THE 

6545
04:05:21,198 --> 04:05:23,334
CCR5 AND HIV, WE FOUND ONE

6546
04:05:23,334 --> 04:05:25,136
STUDY, 50% AND THE OTHER 67% OF

6547
04:05:25,136 --> 04:05:27,104
ANIMALS DID NOT REBOUND AFTER AN

6548
04:05:27,104 --> 04:05:30,207
ATI.

6549
04:05:30,207 --> 04:05:32,009
SO KIND OF THIS RENDITION HERE,

6550
04:05:32,009 --> 04:05:34,111
THIS WAS CALLED OUR GENERATION

6551
04:05:34,111 --> 04:05:35,313
1.0, SO THE TWO GUIDE RNAs

6552
04:05:35,313 --> 04:05:37,949
THAT WERE USED FOR CCR5 IN THOSE

6553
04:05:37,949 --> 04:05:39,450
STUDIES WERE A AND B, BUT REALLY

6554
04:05:39,450 --> 04:05:42,687
OUR STUDIES, WE WANTED TO LOOK

6555
04:05:42,687 --> 04:05:43,955
AT POSSIBLE GUIDE RNAs THAT

6556
04:05:43,955 --> 04:05:48,159
WOULD WORK IN BOTH RHESUS AND

6557
04:05:48,159 --> 04:05:49,093
HUMAN BECAUSE AS YOU'LL SEE FROM

6558
04:05:49,093 --> 04:05:51,262
THE DATA, THE A AND B GUIDES DID

6559
04:05:51,262 --> 04:05:52,930
NOT WORK VERY WELL IN RHESUS.

6560
04:05:52,930 --> 04:05:55,199
SO WE DECIDED TO LOOK AT A

6561
04:05:55,199 --> 04:05:56,901
SECOND GENERATION OF GUIDES THAT

6562
04:05:56,901 --> 04:05:58,402
NOW WITH THE NEWER TECHNOLOGY,

6563
04:05:58,402 --> 04:06:01,605
WE THOUGHT WE COULD DESIGN MORE

6564
04:06:01,605 --> 04:06:06,210
EFFECTIVE GUIDES.

6565
04:06:06,210 --> 04:06:08,913
SO WORKING WITH OUR PARTNERS

6566
04:06:08,913 --> 04:06:11,115
EXCISION BIOTHERAPEUTICS, WE DID

6567
04:06:11,115 --> 04:06:12,383
INSILICO TO LOOK THE A NOMINATED

6568
04:06:12,383 --> 04:06:13,918
OFF TARGET SITES AND THIS IS

6569
04:06:13,918 --> 04:06:17,321
BASICALLY TO SEE IS THERE ANY

6570
04:06:17,321 --> 04:06:18,789
POTENTIAL SITES IN EITHER THE

6571
04:06:18,789 --> 04:06:20,057
HUMAN GENOME OR THE MACAQUE

6572
04:06:20,057 --> 04:06:22,793
GENOME THAT WERE CLOSE TO OUR

6573
04:06:22,793 --> 04:06:23,094
CCR5 GUIDES.

6574
04:06:23,094 --> 04:06:25,196
AND AS YOU CAN SEE FROM THIS

6575
04:06:25,196 --> 04:06:27,264
CHART, WE NEEDED AT LEAST TWO TO

6576
04:06:27,264 --> 04:06:29,400
THREE MISMATCHES BEFORE WE HAD

6577
04:06:29,400 --> 04:06:30,434
ANY GENES THAT WERE SIMILAR.

6578
04:06:30,434 --> 04:06:31,702
SO THIS REALLY IS THE FIRST

6579
04:06:31,702 --> 04:06:34,372
LEVEL OF OUR OFF-TARGET

6580
04:06:34,372 --> 04:06:34,638
ANALYSIS.

6581
04:06:34,638 --> 04:06:39,844
WE'RE ALSO LOCKING AT GUIDE SEQ,

6582
04:06:39,844 --> 04:06:41,579
CAS SEQ, AND ALL OF THESE

6583
04:06:41,579 --> 04:06:43,147
STUDIES BUT THIS IS THE FIRST

6584
04:06:43,147 --> 04:06:43,681
INSILICO METHODS.

6585
04:06:43,681 --> 04:06:45,516
SO NEXT WE WANTED TO LOOK AT IF

6586
04:06:45,516 --> 04:06:48,486
A SINGLE GUIDE RNA COULD CUT, SO

6587
04:06:48,486 --> 04:06:52,456
WHAT WE DID IS A SINGLE GUIDE

6588
04:06:52,456 --> 04:06:54,058
RNA INDEL ANALYSIS.

6589
04:06:54,058 --> 04:06:56,460
WE TOOK OUR GUIDE RNA AND WE

6590
04:06:56,460 --> 04:07:03,267
TOOK CAS9 AND WE SENT THAT OFF

6591
04:07:03,267 --> 04:07:07,304
TO SINTENGO AND THEY'D GIVE US A

6592
04:07:07,304 --> 04:07:10,141
PERCENT I NDEL, EITHER INSERTION

6593
04:07:10,141 --> 04:07:10,908
OR DELETION.

6594
04:07:10,908 --> 04:07:15,913
WE FOUND FROM HERE THAT THREE

6595
04:07:15,913 --> 04:07:17,481
AB8 AND 653 WERE BOTH HIGHLY

6596
04:07:17,481 --> 04:07:19,884
EFFICIENT WITH GIVING UP TO 93%

6597
04:07:19,884 --> 04:07:20,184
INDELLS.

6598
04:07:20,184 --> 04:07:21,385
BUT SINCE WE WANTED TO DO THIS

6599
04:07:21,385 --> 04:07:25,022
NOT JUST LOOKING AT SINGLE

6600
04:07:25,022 --> 04:07:26,357
INDELS, WE WANTED TO HAVE TWO

6601
04:07:26,357 --> 04:07:30,261
GUIDE RNA PAIR, WE THEN DID DUAL

6602
04:07:30,261 --> 04:07:31,262
CCR5 GUIDED RNA EXCISION.

6603
04:07:31,262 --> 04:07:35,166
SO IN ALL OF THESE, YOU WILL SEE

6604
04:07:35,166 --> 04:07:36,000
THE FULL LENGTH PORTION.

6605
04:07:36,000 --> 04:07:37,535
THIS IS A PCR FULL LENGTH

6606
04:07:37,535 --> 04:07:37,868
PORTION.

6607
04:07:37,868 --> 04:07:40,638
YOU'LL SEE THE PORTION OF THE

6608
04:07:40,638 --> 04:07:43,674
GEL AFTER THE CRISPR WAS THERE,

6609
04:07:43,674 --> 04:07:44,875
SO THIS WAS THE CUT SECTION

6610
04:07:44,875 --> 04:07:46,410
AFTER IT WAS REMOVED AND THEN WE

6611
04:07:46,410 --> 04:07:47,545
DID SEQUENCING SO YOU CAN SEE

6612
04:07:47,545 --> 04:07:49,146
THE PART THAT'S ROW MOVED, AND

6613
04:07:49,146 --> 04:07:50,548
HERE YOU CAN SEE THE BREAK

6614
04:07:50,548 --> 04:07:50,781
POINT.

6615
04:07:50,781 --> 04:07:52,983
SO AS IT COMES BACK TOGETHER.

6616
04:07:52,983 --> 04:07:54,885
SO THESE ARE ALL

6617
04:07:54,885 --> 04:07:55,319
SEQUENCE-VERIFIED.

6618
04:07:55,319 --> 04:07:57,488
SO WE DID BOTH HUMAN AND MONKEY

6619
04:07:57,488 --> 04:07:58,789
CELL LINES.

6620
04:07:58,789 --> 04:08:03,160
AND FOUND THAT 388 AND 653, THAT

6621
04:08:03,160 --> 04:08:07,231
COMBINATION WAS EFFICIENT.

6622
04:08:07,231 --> 04:08:09,066
SO AGAIN THIS IS JUST A SUMMARY

6623
04:08:09,066 --> 04:08:11,402
OF A LOT OF DATA THAT WE HAD

6624
04:08:11,402 --> 04:08:13,170
DONE BECAUSE EVERYTHING HAS BEEN

6625
04:08:13,170 --> 04:08:14,071
REPEATED MULTIPLE TIMES.

6626
04:08:14,071 --> 04:08:15,739
THE A AND B THAT WAS USED IN THE

6627
04:08:15,739 --> 04:08:18,809
PAPER IN PNAI IN HUMAN WORKS

6628
04:08:18,809 --> 04:08:20,444
VERY WELL BUT IN MONKEY, THE

6629
04:08:20,444 --> 04:08:21,445
EFFICIENCY WAS VERY LOW.

6630
04:08:21,445 --> 04:08:25,349
SO AS YOU CAN SEE HERE, 388 AND

6631
04:08:25,349 --> 04:08:26,484
653 IS THE PAIR WE'RE MOVING

6632
04:08:26,484 --> 04:08:28,786
FORWARD WITH.

6633
04:08:28,786 --> 04:08:30,988
SO NEXT WE WANTED TO LOOK AT

6634
04:08:30,988 --> 04:08:32,223
THAT SAME -- THOSE SAME PAIRS

6635
04:08:32,223 --> 04:08:36,460
BUT USING EX VIVO ANALYSIS OF

6636
04:08:36,460 --> 04:08:39,463
BOTH MONKEY PMCs AND HUMAN

6637
04:08:39,463 --> 04:08:42,533
PBMCs, AND WE SAW THAT THESE

6638
04:08:42,533 --> 04:08:45,603
TWO GUIDE RNAs WERE REMOVED A

6639
04:08:45,603 --> 04:08:52,810
SECTION OF CCR56789 AND THAT WAS

6640
04:08:52,810 --> 04:08:54,145
CONFIRMED BY SEQUENCING AS YOU

6641
04:08:54,145 --> 04:08:55,980
CAN SEE IN THE MISSING REGION

6642
04:08:55,980 --> 04:08:57,882
WHERE OUR TWO GUIDE RNAs HIT.

6643
04:08:57,882 --> 04:08:59,350
SO OUR NEXT STUDIES ARE REALLY

6644
04:08:59,350 --> 04:09:01,986
TO LOOK AT THIS IN A DIFFERENT

6645
04:09:01,986 --> 04:09:03,954
MOUSE MODEL, SO THE MR. G MOUSE

6646
04:09:03,954 --> 04:09:04,388
MODEL.

6647
04:09:04,388 --> 04:09:08,526
SO IN COLLABORATION WITH LEEHAN

6648
04:09:08,526 --> 04:09:09,693
SHANE OF WASHINGTON UNIVERSITY

6649
04:09:09,693 --> 04:09:11,162
IN ST. LOUIS, HE DEVELOPED WHAT

6650
04:09:11,162 --> 04:09:12,496
WE CALL MR. G MOUSE MODEL.

6651
04:09:12,496 --> 04:09:16,967
SO THIS MOUSE MODEL IS REALLY

6652
04:09:16,967 --> 04:09:20,471
INTERESTING BECAUSE IT HAS

6653
04:09:20,471 --> 04:09:23,140
MYELOID CELLS, B CELLS, T-CELLS

6654
04:09:23,140 --> 04:09:24,775
AND NK CELLS THAT ARE ALL HUMAN,

6655
04:09:24,775 --> 04:09:28,812
AND IT'S VERY CLOSE TO WHAT WE

6656
04:09:28,812 --> 04:09:30,447
SEE IN HUMAN POPULATION.

6657
04:09:30,447 --> 04:09:33,250
SO AS YOU CAN SEE HERE, WE HAVE

6658
04:09:33,250 --> 04:09:36,253
ABOUT 18% CD14 AND ABOUT 9% NK

6659
04:09:36,253 --> 04:09:38,756
CELLS, SO THIS MODEL IS ABLE TO

6660
04:09:38,756 --> 04:09:40,925
HAVE HUMAN CELLS.

6661
04:09:40,925 --> 04:09:42,359
SO THE NEXT THING WE DID IS JUST

6662
04:09:42,359 --> 04:09:45,629
TO LOOK AT CCR5 EXPRESSION ON

6663
04:09:45,629 --> 04:09:47,298
CD4 T-CELLS AND THIS MR. G MOUSE

6664
04:09:47,298 --> 04:09:49,033
MODEL, AND YOU CAN SEE CONTROL

6665
04:09:49,033 --> 04:09:50,968
ANIMALS ARE IN BLUE AND INFECTED

6666
04:09:50,968 --> 04:09:54,138
ARE IN RED.

6667
04:09:54,138 --> 04:09:57,141
AS YOU CAN SEE OVER TIME WE HAVE

6668
04:09:57,141 --> 04:10:01,812
EXPRESSION OF CCR5 -- WE'VE

6669
04:10:01,812 --> 04:10:03,480
STARTED PRELIMINARY STUDIES AND

6670
04:10:03,480 --> 04:10:04,982
THE FIRST EXPERIMENT WE DID WAS

6671
04:10:04,982 --> 04:10:07,284
TO PACKAGE THOSE GUIDE RNAs

6672
04:10:07,284 --> 04:10:10,454
THAT WE CHOSE INTO AV # AND

6673
04:10:10,454 --> 04:10:12,089
AAV6.

6674
04:10:12,089 --> 04:10:15,826
AND THEN WE DELIVERED THOSE TO

6675
04:10:15,826 --> 04:10:18,162
AN ANIMAL AT LOW DOSE, 10 TO

6676
04:10:18,162 --> 04:10:18,796
11AAV PER MASS.

6677
04:10:18,796 --> 04:10:19,997
AS YOU CAN SEE FROM THE RESULTS

6678
04:10:19,997 --> 04:10:21,732
HERE, WE LOOKED AT DAY THREE AND

6679
04:10:21,732 --> 04:10:23,701
DAY 10 AFTER AAV.

6680
04:10:23,701 --> 04:10:24,468
AND PRELIMINARY RESULTS SHOW

6681
04:10:24,468 --> 04:10:26,570
THAT WE DO HAVE A SIGNIFICANT

6682
04:10:26,570 --> 04:10:30,674
DECREASE IN CCR5 SO WE DO HAVE

6683
04:10:30,674 --> 04:10:35,312
EDITING AND REMOVAL OF CCR5.

6684
04:10:35,312 --> 04:10:36,914
THIS IS PRIMARY DATA SO NOW

6685
04:10:36,914 --> 04:10:38,382
WE'RE LOOKING AT A HIGHER DOSE

6686
04:10:38,382 --> 04:10:39,817
AND ALSO GOING TO DO SOME MORE

6687
04:10:39,817 --> 04:10:40,985
EXTENSIVE STUDIES BUT THIS IS

6688
04:10:40,985 --> 04:10:41,952
JUST TO SHOW THAT IT IS WORKING

6689
04:10:41,952 --> 04:10:42,953
IN THIS MODEL.

6690
04:10:42,953 --> 04:10:47,191
SO FUTURE STUDIES WILL USE THESE

6691
04:10:47,191 --> 04:10:50,261
CCR5S AND THE MISTRG MOUSE MODEL

6692
04:10:50,261 --> 04:10:51,695
AND ALSO POTENTIALLY IN THE

6693
04:10:51,695 --> 04:10:53,631
NON-HUMAN PRIMATE MODEL IF IT

6694
04:10:53,631 --> 04:10:56,200
MEETS OUR GO/NO-GO CRITERIA.

6695
04:10:56,200 --> 04:10:57,835
AGAIN I SAID WE'RE USING A

6696
04:10:57,835 --> 04:11:00,237
NUMBER OF OTHER TARGETS IN

6697
04:11:00,237 --> 04:11:05,509
RETROVIRF2 AND THOSE INCLUDE PD5

6698
04:11:05,509 --> 04:11:06,277
AND CD16.

6699
04:11:06,277 --> 04:11:09,980
SO LOOKING AT NK AND

6700
04:11:09,980 --> 04:11:10,347
CD8 MODERATION.

6701
04:11:10,347 --> 04:11:16,720
SO I'M GOING TO PASS IT OVER TO

6702
04:11:16,720 --> 04:11:18,255
DR. KHALILLI, WHO WILL TALK

6703
04:11:18,255 --> 04:11:22,893
ABOUT RF3.

6704
04:11:22,893 --> 04:11:25,529
>> MY NEXT SLIDE IS PLAIN

6705
04:11:25,529 --> 04:11:30,000
LANGUAGE SUMMARY, BASICALLY

6706
04:11:30,000 --> 04:11:31,735
ILLUSTRATING -- CAN ELIMINATE

6707
04:11:31,735 --> 04:11:33,804
THE VIRUS FROM THE WHOLE

6708
04:11:33,804 --> 04:11:36,507
CHROMOSOME BY THE CRISPR, AND AS

6709
04:11:36,507 --> 04:11:37,975
MENTIONED EARLIER, THAT IT SEEMS

6710
04:11:37,975 --> 04:11:39,810
THAT AT LEAST IN THE

6711
04:11:39,810 --> 04:11:42,012
EXPERIMENTAL ANIMALS, LARGE AND

6712
04:11:42,012 --> 04:11:48,052
SMALL ANIMAL, IT'S POSSIBLE TH 

6713
04:11:48,052 --> 04:11:48,886
THAT -- TO THE CURE.

6714
04:11:48,886 --> 04:11:50,554
THE PROBLEM THAT WE ARE FACING

6715
04:11:50,554 --> 04:11:53,957
WITH THE HIV IN MY VIEW IN THAT

6716
04:11:53,957 --> 04:11:56,560
APPROACH IS THE PRESENCE OF THE

6717
04:11:56,560 --> 04:11:57,227
INCORPORATED VIRAL DNA.

6718
04:11:57,227 --> 04:12:00,998
SO BASICALLY, IF YOU CAN THINK

6719
04:12:00,998 --> 04:12:04,835
THAT THE INFECTIOUS DISEASE

6720
04:12:04,835 --> 04:12:06,437
SPACE CHANGES, BECOME LIKE A

6721
04:12:06,437 --> 04:12:08,238
GENETIC DISEASE, IF THAT IS THE

6722
04:12:08,238 --> 04:12:10,107
GENETIC APPROACH, NOW YOU HAVE A

6723
04:12:10,107 --> 04:12:12,309
BAD GENE IN YOUR CHROMOSOME,

6724
04:12:12,309 --> 04:12:14,078
YOU'VE GOT TO FIND A WAY TO

6725
04:12:14,078 --> 04:12:15,145
INACTIVATE THE BAD GENE.

6726
04:12:15,145 --> 04:12:16,947
SO THAT CAN BE ACCOMPLISHED BY

6727
04:12:16,947 --> 04:12:21,485
THE CHRIS  CRISPR TECHNOLOGY, BE

6728
04:12:21,485 --> 04:12:25,189
CRISPR/CAS 9 IS BASICALLY IN THE

6729
04:12:25,189 --> 04:12:27,958
NUCLEUS BUT CRISPR/CAS

6730
04:12:27,958 --> 04:12:28,625
9 BASICALLY APPROPRIATE FOR THIS

6731
04:12:28,625 --> 04:12:30,461
KIND OF STUDY IS THE GUIDE

6732
04:12:30,461 --> 04:12:31,328
RNAs.

6733
04:12:31,328 --> 04:12:34,498
RNAs WHICH BASICALLY EDUCATE

6734
04:12:34,498 --> 04:12:37,334
IN THE NUCLEUS THAT -- TO CUT

6735
04:12:37,334 --> 04:12:38,268
WITHOUT ANY COLLATERAL DAMAGE

6736
04:12:38,268 --> 04:12:39,870
THE OTHER PART OF THE CELLULAR

6737
04:12:39,870 --> 04:12:40,771
GENE.

6738
04:12:40,771 --> 04:12:43,273
AND THIS CLEAVAGE SHOULD BE VERY

6739
04:12:43,273 --> 04:12:45,476
EFFICIENT AND SPECIFIC.

6740
04:12:45,476 --> 04:12:47,711
SO RF3 IS VERY MUCH FOCUSING ON

6741
04:12:47,711 --> 04:12:50,381
THE DEVELOPING OF THE GUIDE

6742
04:12:50,381 --> 04:12:52,049
RNAs, WHICH IS APPROPRIATE FOR

6743
04:12:52,049 --> 04:12:55,853
THE CLEAVAGE OF THE SIV, SIV

6744
04:12:55,853 --> 04:12:57,855
1 FOR THE STUDIES IN THE MONKEY,

6745
04:12:57,855 --> 04:13:00,457
AND THE HIV-1 FOR STUDIES IN

6746
04:13:00,457 --> 04:13:05,028
NON-HUMAN PRIMATE, -- MICE WHICH

6747
04:13:05,028 --> 04:13:07,030
MENTIONED ABOUT THAT.

6748
04:13:07,030 --> 04:13:10,067
AND THAT IS MISTRG MICE

6749
04:13:10,067 --> 04:13:16,540
DEVELOPED BY RF2 MEMBERS.

6750
04:13:16,540 --> 04:13:17,408
WITH THAT KNOWING, I'M GOING TO

6751
04:13:17,408 --> 04:13:19,510
SHOW YOU THE MAP FIRST FOR THE

6752
04:13:19,510 --> 04:13:20,577
SRV THAT WE ARE USING FOR

6753
04:13:20,577 --> 04:13:21,545
DEVELOPING OF THOSE GUIDE

6754
04:13:21,545 --> 04:13:25,249
RNAs.

6755
04:13:25,249 --> 04:13:29,987
SO WE WE IDENTIFY THE GROUP OF

6756
04:13:29,987 --> 04:13:34,558
REGIONS WITHIN THE BARCODE SIV

6757
04:13:34,558 --> 04:13:36,860
WHICH COULD BE USED FOR THE

6758
04:13:36,860 --> 04:13:38,529
TARGETING AND DEVELOPMENT OF THE

6759
04:13:38,529 --> 04:13:39,062
GUIDE RNA.

6760
04:13:39,062 --> 04:13:40,931
AS I MENTIONED EARLIER, OUR

6761
04:13:40,931 --> 04:13:43,233
APPROACH IS USING MULTIPLEX OF

6762
04:13:43,233 --> 04:13:45,736
THE GUIDE RNA IN ORDER TO EXCISE

6763
04:13:45,736 --> 04:13:49,339
THE SEGMENTS OF THE -- GENOME.

6764
04:13:49,339 --> 04:13:51,875
WL THAT APPROACH THEN YOU CAN

6765
04:13:51,875 --> 04:13:54,812
ELIMINATE AN INTRODUCTION AND

6766
04:13:54,812 --> 04:13:56,313
MUTATIONS WHICH CAUSES BASICALLY

6767
04:13:56,313 --> 04:13:58,749
MUTANT VIRUS COMING OUT LATER ON

6768
04:13:58,749 --> 04:14:00,851
FROM THE CELL.

6769
04:14:00,851 --> 04:14:05,889
BUT IF THE BARCODE ALSO SIV, THE

6770
04:14:05,889 --> 04:14:07,591
CHALLENGE IS THAT WE HAVE TO USE

6771
04:14:07,591 --> 04:14:09,960
AREAS OF THE VIRUS WHICH DOES

6772
04:14:09,960 --> 04:14:12,329
NOT REMOVE OUR BARCODE SEQUENCE.

6773
04:14:12,329 --> 04:14:14,264
THAT IS IMPORTANT BECAUSE THAT

6774
04:14:14,264 --> 04:14:16,200
BARCODE HELPS US UNDERSTAND

6775
04:14:16,200 --> 04:14:17,868
ABOUT THE RESERVOIR.

6776
04:14:17,868 --> 04:14:19,603
THE VIRUS IS COMING UP FROM THE

6777
04:14:19,603 --> 04:14:25,542
RESERVOIR.

6778
04:14:25,542 --> 04:14:27,444
NICHE LE THEN WE STARTED USING

6779
04:14:27,444 --> 04:14:30,581
SINGLE GUIDE RNAs, REGION

6780
04:14:30,581 --> 04:14:32,349
WITHIN THE BARCODED SIV ONE

6781
04:14:32,349 --> 04:14:35,786
WHICH CAN BE USED FOR AT LEAST

6782
04:14:35,786 --> 04:14:38,222
ONE GUIDE RNA AND THEN WITH THE

6783
04:14:38,222 --> 04:14:39,756
HIGH EFFICIENCY OF THE INDEL

6784
04:14:39,756 --> 04:14:40,290
MUTATIONS.

6785
04:14:40,290 --> 04:14:42,092
AND THEN WE IDENTIFY THOSE

6786
04:14:42,092 --> 04:14:44,228
REGION AS YOU SEE BY THE ARROWS

6787
04:14:44,228 --> 04:14:47,097
ON THE TOP OF THE BARS, AND WE

6788
04:14:47,097 --> 04:14:52,336
USED THE PAIR, THAT ONE, WITH

6789
04:14:52,336 --> 04:14:54,538
THE SECOND ONE WHICH HAS ALSO

6790
04:14:54,538 --> 04:14:57,040
HIGH EFFICIENCY OF THE INDEL

6791
04:14:57,040 --> 04:14:59,877
MUTATION.

6792
04:14:59,877 --> 04:15:04,948
THEN WE -- WHETHER OR NOT YOU

6793
04:15:04,948 --> 04:15:06,817
HAVE AN EXCISION OF THE DNA

6794
04:15:06,817 --> 04:15:09,553
FRAGMENT FROM THE CHROMOSOMES OF

6795
04:15:09,553 --> 04:15:11,688
THE GENES, INCORPORATED THE

6796
04:15:11,688 --> 04:15:22,199
EXAMPLE OF THAT ONE IS -- THIS

6797
04:15:29,706 --> 04:15:31,108
IS BASICALLY FULL LENGTH AND

6798
04:15:31,108 --> 04:15:33,110
SOME OF THEM ARE OBVIOUSLY --

6799
04:15:33,110 --> 04:15:34,444
IT'S AN INDEL MUTATION, AND THIS

6800
04:15:34,444 --> 04:15:40,450
IS THE EC EXCISION ASSAY, NOT TE

6801
04:15:40,450 --> 04:15:41,351
EXCISE FRAGMENT.

6802
04:15:41,351 --> 04:15:46,490
THE FRAGMENT WHICH REMAINS AFTER

6803
04:15:46,490 --> 04:15:49,760
EXCISION -- SO YOU SEE THAT ONE,

6804
04:15:49,760 --> 04:15:51,061
AND THEN I WENT THROUGH THE

6805
04:15:51,061 --> 04:15:52,930
WHOLE SCREENING BASED ON THE

6806
04:15:52,930 --> 04:15:55,032
INFORMATION FOR INSILICO

6807
04:15:55,032 --> 04:15:58,068
ANALYSIS TO IEND GUY THE -- GAG

6808
04:15:58,068 --> 04:15:59,202
AS POTENTIAL FOR THE MOVING

6809
04:15:59,202 --> 04:16:05,642
FORWARD FOR THE IN VIVO STUDIES.

6810
04:16:05,642 --> 04:16:09,179
SO BASED ON THAT STUDY, WE

6811
04:16:09,179 --> 04:16:11,214
IDENTIFIED THAT 31% OF THE CELLS

6812
04:16:11,214 --> 04:16:15,052
THAT WE USE HAS A COMPLETE

6813
04:16:15,052 --> 04:16:19,022
EXCISION REMOVAL OF THE REGION

6814
04:16:19,022 --> 04:16:21,491
WITHIN THE -- WITHOUT ANY

6815
04:16:21,491 --> 04:16:23,260
COLLATERAL DAMAGE OR TOXICITY

6816
04:16:23,260 --> 04:16:26,730
ASSOCIATED WITH THE EXCISION.

6817
04:16:26,730 --> 04:16:28,031
SO NOW WE HAVE A PRODUCT.

6818
04:16:28,031 --> 04:16:30,767
THAT PRODUCT RIGHT NOW IS IN

6819
04:16:30,767 --> 04:16:35,472
PROCESS OF BEING PA PACKAGED ON

6820
04:16:35,472 --> 04:16:37,140
AAV9, T-CELL TROPHIC.

6821
04:16:37,140 --> 04:16:38,675
THIS IS THE AREA OF THE

6822
04:16:38,675 --> 04:16:45,215
RF3 WHICH IS BASICALLY PERFORMED

6823
04:16:45,215 --> 04:16:49,820
BY HARUN CHAN AND ALSO MIKE

6824
04:16:49,820 --> 04:16:51,355
PARSON, AND THEN THEY'LL

6825
04:16:51,355 --> 04:16:52,422
COLLABORATE WITH US AND THEY'RE

6826
04:16:52,422 --> 04:16:54,358
TRYING TO MAKE AAV9 WHICH HAS A

6827
04:16:54,358 --> 04:16:57,794
HIGH AFFINITY FOR CD4 CELLS.

6828
04:16:57,794 --> 04:16:59,396
SO ONCE THE PACKAGE IS DONE,

6829
04:16:59,396 --> 04:17:03,634
WE'RE GOING TO MOVE FORWARD WITH

6830
04:17:03,634 --> 04:17:07,070
THE MACAQUE STUDIES.

6831
04:17:07,070 --> 04:17:09,806
IN THE PARALLEL, WE ALSO -- THE

6832
04:17:09,806 --> 04:17:11,942
SAME KIND OF ROAD MAP FOR THE

6833
04:17:11,942 --> 04:17:12,576
MICE STUDIES.

6834
04:17:12,576 --> 04:17:14,878
IN THIS CASE OBVIOUSLY WE'RE

6835
04:17:14,878 --> 04:17:15,879
USING HIV-1.

6836
04:17:15,879 --> 04:17:18,782
AND THE FIRST ONE WE DID WAS

6837
04:17:18,782 --> 04:17:19,983
THAT THEY IDENTIFY SEVERAL

6838
04:17:19,983 --> 04:17:21,418
REGIONS WITHIN THE HIV WHICH CAN

6839
04:17:21,418 --> 04:17:25,222
BE TARGETED FOR THE EXCISION

6840
04:17:25,222 --> 04:17:30,293
BASED ON THE PRESENCE OF THE --

6841
04:17:30,293 --> 04:17:32,262
BASED ON THE PRESENCE OF THE PAM

6842
04:17:32,262 --> 04:17:32,729
SEQUENCE.

6843
04:17:32,729 --> 04:17:34,431
AND WHEN YOU ALIGN THOSE

6844
04:17:34,431 --> 04:17:37,334
REGIONS, WHICH IS ABOUT 500,

6845
04:17:37,334 --> 04:17:39,469
WITH THE SEQUENCES FROM THE

6846
04:17:39,469 --> 04:17:46,376
LOS ALAMOS STUDIES, YOU IDENTIFY

6847
04:17:46,376 --> 04:17:48,378
14 OF THEM PROBABLY PROVIDE THE

6848
04:17:48,378 --> 04:17:49,680
POTENTIAL FOR THE TARGETING BY

6849
04:17:49,680 --> 04:17:52,516
THE CRISPR/CAS 9.

6850
04:17:52,516 --> 04:17:56,286
AND THEN ALTHOUGH THAT'S 14, WE

6851
04:17:56,286 --> 04:18:00,857
USE SOME OF THEM, AND BASICALLY

6852
04:18:00,857 --> 04:18:02,292
THE INDEL MUTATIONS, AND AS YOU

6853
04:18:02,292 --> 04:18:04,795
SEE HERE, AND THEN SELECTED THE

6854
04:18:04,795 --> 04:18:06,697
FOUR OF THEM FOR THE SUBSEQUENT

6855
04:18:06,697 --> 04:18:08,365
STUDIES WHICH IS ECK VEE VO.

6856
04:18:08,365 --> 04:18:09,633
I'M GOING TO STOP HERE, I'M

6857
04:18:09,633 --> 04:18:14,638
GOING TO INVITE DR. SARIYER TO

6858
04:18:14,638 --> 04:18:16,306
TALK ABOUT THE EX VIVO

6859
04:18:16,306 --> 04:18:16,606
EXPERIMENT.

6860
04:18:16,606 --> 04:18:17,007
THANK YOU.

6861
04:18:17,007 --> 04:18:24,514
[APPLAUSE]

6862
04:18:24,514 --> 04:18:30,253
>> COMING DOWN TO FOUR
PRIMARY

6863
04:18:30,253 --> 04:18:34,458
GUIDE RNAs THAT WE THINK MIGHT

6864
04:18:34,458 --> 04:18:35,826
BE USEFUL FOR MOVING FORWARD

6865
04:18:35,826 --> 04:18:37,828
WITH THE IMMUNOSTUDIES.

6866
04:18:37,828 --> 04:18:41,098
SO ANOTHER IMPORTANT PART OF OUR

6867
04:18:41,098 --> 04:18:42,833
WORKFLOW IS EX-A VERY VO

6868
04:18:42,833 --> 04:18:43,333
EDITING.

6869
04:18:43,333 --> 04:18:46,470
SO THIS STARTS WITH THE DONOR

6870
04:18:46,470 --> 04:18:48,538
PBMCs AND WE ARE IN

6871
04:18:48,538 --> 04:18:50,941
COLLABORATION WITH DREXEL

6872
04:18:50,941 --> 04:18:55,545
UNIVERSITY.

6873
04:18:55,545 --> 04:18:57,280
WE FORM OUR COHORTS, AND IN THIS

6874
04:18:57,280 --> 04:19:00,350
EXAMPLE YOU SEE 34 DONOR CELLS,

6875
04:19:00,350 --> 04:19:02,018
FRESHLY OBTAINED FROM THE

6876
04:19:02,018 --> 04:19:03,520
DONORS, AND OUR WORKFLOW

6877
04:19:03,520 --> 04:19:06,022
INVOLVES ISOLATING CD4 T-CELLS

6878
04:19:06,022 --> 04:19:09,926
AND EXPANSION OF THOSE T-CELLS

6879
04:19:09,926 --> 04:19:12,829
FOR SEVEN DAYS BY INDUCING THEM

6880
04:19:12,829 --> 04:19:15,232
AND ALSO BEFORE THE UTILIZATION

6881
04:19:15,232 --> 04:19:17,968
FOR EX VIVO ANALYSIS, IT WAS --

6882
04:19:17,968 --> 04:19:19,569
THE EXPANSIONS.

6883
04:19:19,569 --> 04:19:21,705
AND THEN ONCE THOSE CELLS ARE

6884
04:19:21,705 --> 04:19:23,774
EXPANDED, WE UTILIZED THEM FOR

6885
04:19:23,774 --> 04:19:25,742
INDEL AS WELL AS EXCISION

6886
04:19:25,742 --> 04:19:29,079
ANALYSIS TO TEST FOR GUIDE RNA

6887
04:19:29,079 --> 04:19:32,783
ACTIVITIES.

6888
04:19:32,783 --> 04:19:34,684
SO AGAIN THESE ARE OUR FOUR

6889
04:19:34,684 --> 04:19:35,886
CANDIDATE GUIDE RNAs FOR

6890
04:19:35,886 --> 04:19:38,855
SCREENING IN EX VIVO, AND OUR

6891
04:19:38,855 --> 04:19:43,426
WORKFLOW INVOLVED RMB

6892
04:19:43,426 --> 04:19:44,795
RIBONUCLEAR PROTEIN -- T-CELLS

6893
04:19:44,795 --> 04:19:47,798
ARE VERY HARD TO TRANSFECT OR

6894
04:19:47,798 --> 04:19:50,333
TRANSDUCE PRIMARY T-CELLS, SO WE

6895
04:19:50,333 --> 04:19:52,202
FOUND THAT RMP IS THE BEST

6896
04:19:52,202 --> 04:19:58,074
METHOD USING RECOMBINANT CASS #

6897
04:19:58,074 --> 04:20:01,178
PROTEIN INTRODUCING TO THE CELLS

6898
04:20:01,178 --> 04:20:03,780
USING EITHER -- ELECTRO -- AND

6899
04:20:03,780 --> 04:20:07,417
GOING FROM THEREFORE INDEL AND

6900
04:20:07,417 --> 04:20:07,851
EXON ANALYSIS.

6901
04:20:07,851 --> 04:20:10,153
I NEED TO NOTE HERE THAT THE

6902
04:20:10,153 --> 04:20:11,788
GENOMIC DATA OBTAINED FROM THOSE

6903
04:20:11,788 --> 04:20:15,091
STUDIES ALSO MOVES TO --

6904
04:20:15,091 --> 04:20:17,394
APPROACH THE FULL -- SEQUENCING,

6905
04:20:17,394 --> 04:20:19,129
GUIDE COMPATIBILITY ASSAYS AND

6906
04:20:19,129 --> 04:20:20,564
VARIOUS ALGORITHMS FOR ON AND

6907
04:20:20,564 --> 04:20:22,365
OFF TARGET ANALYSIS USING GUIDE

6908
04:20:22,365 --> 04:20:24,367
SEQ, AND THOSE STUDIES ARE ALSO

6909
04:20:24,367 --> 04:20:29,840
LED BY DR. WIGDAL'S GROUP AT

6910
04:20:29,840 --> 04:20:31,641
DREXEL UNIVERSITY.

6911
04:20:31,641 --> 04:20:36,079
SO THIS IS AN EXAMPLE OF INDEL,

6912
04:20:36,079 --> 04:20:39,482
IT INVOLVES OUR TARGET SITE

6913
04:20:39,482 --> 04:20:42,686
SEQUENCING AND RUNNING THROUGH

6914
04:20:42,686 --> 04:20:43,253
THE -- ANALYSIS.

6915
04:20:43,253 --> 04:20:45,522
THIS GIVES US VERY NICELY WHAT

6916
04:20:45,522 --> 04:20:50,861
INDELS AND YOU KNOW EDITS ARE

6917
04:20:50,861 --> 04:20:56,032
FORMED -- FOR THIS PARTICULAR

6918
04:20:56,032 --> 04:20:57,434
CANDIDATE GUIDE RNA WHICH IS THE

6919
04:20:57,434 --> 04:20:59,669
LTR REGION OF THE HIV, AND BASED

6920
04:20:59,669 --> 04:21:01,872
ON THIS, WE GET A PERCENT INDEL

6921
04:21:01,872 --> 04:21:06,209
ACTIVITY, WHICH IS HERE 21%.

6922
04:21:06,209 --> 04:21:08,044
AFTER SECRETING ALL THE RNA

6923
04:21:08,044 --> 04:21:09,179
CANDIDATES WITH 16 DONORS IN

6924
04:21:09,179 --> 04:21:14,317
THIS TABLE AS AN EXAMPLE, WE GET

6925
04:21:14,317 --> 04:21:15,485
VARIOUS ACTIVITIES RANGING FROM

6926
04:21:15,485 --> 04:21:17,654
A FEW PERCENT TO 98%, DEPENDING

6927
04:21:17,654 --> 04:21:23,693
ON THE DONOR SEQUENCE.

6928
04:21:23,693 --> 04:21:26,963
TO GIVE YOU AN IDEA ABOUT HOW

6929
04:21:26,963 --> 04:21:29,966
THESE PARTICULAR GUIDE RNAs

6930
04:21:29,966 --> 04:21:33,703
PERFORM, QUANT QUANTITATIVE EXCN

6931
04:21:33,703 --> 04:21:35,672
OR INDEL ACTIVITIES TO MAKE A

6932
04:21:35,672 --> 04:21:36,239
FULL DECISION.

6933
04:21:36,239 --> 04:21:40,543
SECOND APPROACH IS MENTIONED,

6934
04:21:40,543 --> 04:21:42,212
TWO GUIDE RNAs TO REMOVE A

6935
04:21:42,212 --> 04:21:45,382
CHUNK OF HIV, NOT GIVING HIV A

6936
04:21:45,382 --> 04:21:46,716
CHANCE TO REPLICATE OR REABT

6937
04:21:46,716 --> 04:21:47,150
VAIT.

6938
04:21:47,150 --> 04:21:51,788
SO IN THIS EXAMPLE, VERIFYING

6939
04:21:51,788 --> 04:21:55,325
THAT THERE IS EXCISION ACTIVITY.

6940
04:21:55,325 --> 04:21:57,193
THE TABLE HERE SUMMARIZES THOSE

6941
04:21:57,193 --> 04:21:58,862
RESULTS FROM 16 DONORS, AND

6942
04:21:58,862 --> 04:22:04,367
GIVES US A RANGE BETWEEN 8 TOLL

6943
04:22:04,367 --> 04:22:06,269
75% EXCISION ACTIVITY AMONG THE

6944
04:22:06,269 --> 04:22:08,038
16 DONORS.

6945
04:22:08,038 --> 04:22:09,606
WITH THIS, I WOULD LIKE TO

6946
04:22:09,606 --> 04:22:11,107
ACKNOWLEDGE ALL THE

6947
04:22:11,107 --> 04:22:17,147
COLLABORATORS FOR RF3.

6948
04:22:17,147 --> 04:22:19,649
DREXEL GROUP, HARVARD GROUP,

6949
04:22:19,649 --> 04:22:20,750
WASHINGTON UNIVERSITY, OUR

6950
04:22:20,750 --> 04:22:23,086
TEMPLE GROUP AND EXCISION

6951
04:22:23,086 --> 04:22:23,420
THERAPEUTICS.

6952
04:22:23,420 --> 04:22:23,720
THANK YOU.

6953
04:22:23,720 --> 04:22:33,029
[APPLAUSE]

6954
04:22:33,029 --> 04:22:34,864
>> HI, EVERYONE.

6955
04:22:34,864 --> 04:22:36,333
I'M KATE, THE COMMUNITY

6956
04:22:36,333 --> 04:22:37,300
ENGAGEMENT COORDINATOR FOR

6957
04:22:37,300 --> 04:22:40,570
CRISPR FOR CURE.

6958
04:22:40,570 --> 04:22:42,105
I AM GOING TO FLY THROUGH THIS A

6959
04:22:42,105 --> 04:22:43,406
BIT QUICKLY BECAUSE WE ARE

6960
04:22:43,406 --> 04:22:44,607
RUNNING OUT OF TIME.

6961
04:22:44,607 --> 04:22:46,142
THE MISSION OF OUR COMMUNITY

6962
04:22:46,142 --> 04:22:47,577
ENGAGEMENT COMPONENT IS TO

6963
04:22:47,577 --> 04:22:49,212
FOSTER AND MAINTAIN PARTNERSHIPS

6964
04:22:49,212 --> 04:22:50,947
AND OPEN COMMUNICATION BETWEEN

6965
04:22:50,947 --> 04:22:52,716
COMMUNITY MEMBERS AND RESEARCHER

6966
04:22:52,716 --> 04:22:53,950
WITHIN THE CRISPR FOR CURE

6967
04:22:53,950 --> 04:22:56,019
NETWORK AND ALSO TO ENHANCE HOW

6968
04:22:56,019 --> 04:22:57,554
THE WORK CAN TARGET GENETIC

6969
04:22:57,554 --> 04:22:59,756
MATERIAL FOR HIV EDUCATION,

6970
04:22:59,756 --> 04:23:00,657
PREVENTION, TREATMENT AND

6971
04:23:00,657 --> 04:23:01,791
RESEARCH ACTIVITIES REFLECTING

6972
04:23:01,791 --> 04:23:03,426
BOTH INVESTIGATORS' INTERESTS

6973
04:23:03,426 --> 04:23:05,428
AND COMMUNITY ENGAGEMENT.

6974
04:23:05,428 --> 04:23:08,064
SO THE YEAR TWO MILESTONES.

6975
04:23:08,064 --> 04:23:10,600
WE CREATED AND PASSED THE CAB

6976
04:23:10,600 --> 04:23:10,900
BYLAWS.

6977
04:23:10,900 --> 04:23:12,936
WE HAVE A NEW COMMUNITY PARTNER,

6978
04:23:12,936 --> 04:23:16,339
WILLIAM WEY, LGBTQ COMMUNITY

6979
04:23:16,339 --> 04:23:18,041
CENTER.

6980
04:23:18,041 --> 04:23:19,876
WE HAVE INITIATED THE PROJECT OF

6981
04:23:19,876 --> 04:23:21,311
GLOSSARY OF SCIENTIFIC TERMS,

6982
04:23:21,311 --> 04:23:22,979
AND WE ALSO ARE IN THE PROCESS

6983
04:23:22,979 --> 04:23:27,183
OF EDITING DOWN THE COFFEE WITH

6984
04:23:27,183 --> 04:23:29,219
CRISPR FOR CURE VIDEO, AS WELL

6985
04:23:29,219 --> 04:23:31,721
AS PARTICIPATION IN THE LTS

6986
04:23:31,721 --> 04:23:32,088
STUDY.

6987
04:23:32,088 --> 04:23:33,656
COMMUNITY ADVISORY BOARD.

6988
04:23:33,656 --> 04:23:36,559
SO WE DID HAVE OUR FIRST BOOK

6989
04:23:36,559 --> 04:23:37,560
CLUB MEETING.

6990
04:23:37,560 --> 04:23:42,298
HELD AT THE WILLIAM WAY CENTER.

6991
04:23:42,298 --> 04:23:43,466
IT BRINGS TOGETHER RESEARCHERS

6992
04:23:43,466 --> 04:23:44,768
AND COMMUNITY MEMBERS IN

6993
04:23:44,768 --> 04:23:45,635
DISCUSSING CODE BREAKER, THE

6994
04:23:45,635 --> 04:23:46,102
BOOK.

6995
04:23:46,102 --> 04:23:49,506
WE DID PARTICIPATE IN THE U.S.

6996
04:23:49,506 --> 04:23:51,474
CHA IN D.C.  THIS YEAR, AND THEN

6997
04:23:51,474 --> 04:23:53,777
WE ALSO SPONSORED THE

6998
04:23:53,777 --> 04:23:56,179
RESTORATIVE JUSTICE WORKSHOP IN

6999
04:23:56,179 --> 04:23:57,614
COLLABORATION WITH THE

7000
04:23:57,614 --> 04:24:01,117
RESTORATIVE PRACTICES AT PNN AS

7001
04:24:01,117 --> 04:24:02,752
WELL AS MYSELF FACILITATING A

7002
04:24:02,752 --> 04:24:03,753
COMMUNICATIONS WORKSHOP AND THEN

7003
04:24:03,753 --> 04:24:05,722
OBVIOUSLY THE VIDEO.

7004
04:24:05,722 --> 04:24:07,690
SO THE BOOK CLUB.

7005
04:24:07,690 --> 04:24:09,325
SESSION ONE, WE DISCUSSED PARTS

7006
04:24:09,325 --> 04:24:10,693
ONE AND TWO OF CODE BREAKER.

7007
04:24:10,693 --> 04:24:12,629
WE BROUGHT EVERYBODY IN, WE

7008
04:24:12,629 --> 04:24:13,296
SERVED FOOD AND WE'RE GOING TO

7009
04:24:13,296 --> 04:24:15,598
BE DOING OUR SECOND SESSION.

7010
04:24:15,598 --> 04:24:17,567
THE BOOK CLUB IS MODERATED BY

7011
04:24:17,567 --> 04:24:20,270
ONE OF OUR CAB MEMBERS.

7012
04:24:20,270 --> 04:24:21,971
AND THEN THE RESTORATIVE JUSTICE

7013
04:24:21,971 --> 04:24:24,074
AND COMMUNICATION WORKSHOP,

7014
04:24:24,074 --> 04:24:25,041
RESTORATIVE PRACTICES IS A

7015
04:24:25,041 --> 04:24:26,476
COMMUNITY DEVELOPMENT FRAMEWORK

7016
04:24:26,476 --> 04:24:28,044
THAT FOCUSES ON BUILDING

7017
04:24:28,044 --> 04:24:29,245
RELATIONSHIPS THROUGH ONGOING

7018
04:24:29,245 --> 04:24:30,180
SUSTAINED INTERACTIONS.

7019
04:24:30,180 --> 04:24:32,082
CAB LEADERS AND CAB MEMBERS ARE

7020
04:24:32,082 --> 04:24:33,149
BROUGHT INTO COMMUNITY

7021
04:24:33,149 --> 04:24:34,484
DISCUSSIONS LEARNING HOW TO BE

7022
04:24:34,484 --> 04:24:36,453
BETTER COMMUNICATORS AND MORE

7023
04:24:36,453 --> 04:24:37,253
PURPOSEFUL PARTICIPANTS IN THEIR

7024
04:24:37,253 --> 04:24:37,887
OWN WORK.

7025
04:24:37,887 --> 04:24:38,955
THESE WORKSHOPS AND

7026
04:24:38,955 --> 04:24:40,290
PRESENTATIONS ARE SKILL-BASED

7027
04:24:40,290 --> 04:24:41,357
OFFERINGS REQUESTED BY THE

7028
04:24:41,357 --> 04:24:43,693
ACTUAL CAB MEMBERS.

7029
04:24:43,693 --> 04:24:45,562
SO THE CREATION OF THE COFFEE

7030
04:24:45,562 --> 04:24:49,933
WITH CRISPR FOR CURE VIDEO IS

7031
04:24:49,933 --> 04:24:51,367
JUST CONVERSATIONS, VERY CASUAL

7032
04:24:51,367 --> 04:24:52,001
CONVERSATIONS BETWEEN THE

7033
04:24:52,001 --> 04:24:53,236
COMMUNITY MEMBERS AND

7034
04:24:53,236 --> 04:24:55,305
RESEARCHERS ABOUT HIV CURE

7035
04:24:55,305 --> 04:24:56,506
RESEARCH WITH THE FOCUS ON

7036
04:24:56,506 --> 04:24:57,107
CRISPR.

7037
04:24:57,107 --> 04:25:02,011
WE'RE GOING TO BE -- TO LAUNCH

7038
04:25:02,011 --> 04:25:06,583
DISCUSSIONS ABOUT HIV CURE AND

7039
04:25:06,583 --> 04:25:08,017
CRISPR.

7040
04:25:08,017 --> 04:25:09,886
WE ALSO PARTICIPATED IN THE LONG

7041
04:25:09,886 --> 04:25:13,356
TERM SURVIVOR STUDY AND OUR

7042
04:25:13,356 --> 04:25:14,424
COMMUNITY PARTNERS.

7043
04:25:14,424 --> 04:25:16,292
WE ARE NOW PARTNERED WITH THE

7044
04:25:16,292 --> 04:25:20,563
FREE LIBRARY OF FILL DEFINITELYY

7045
04:25:20,563 --> 04:25:22,098
YAL COLORS ORGANIZATION, AND THE

7046
04:25:22,098 --> 04:25:25,068
WILLIAM WAY COMMUNITY CENTER.

7047
04:25:25,068 --> 04:25:27,036
CHALLENGES AND SUCCESSES.

7048
04:25:27,036 --> 04:25:28,371
I THINK RECRUITMENT AND

7049
04:25:28,371 --> 04:25:30,440
RETENTION HAS BEEN DIFFICULT FOR

7050
04:25:30,440 --> 04:25:31,107
US.

7051
04:25:31,107 --> 04:25:33,143
WE'RE TRYING TO -- THERE'S --

7052
04:25:33,143 --> 04:25:34,577
DUE TO THE PRESENCE OF AS IT

7053
04:25:34,577 --> 04:25:35,812
STATES, BECAUSE THERE'S SO MANY

7054
04:25:35,812 --> 04:25:38,882
CABS IN PHILADELPHIA, THERE'S A

7055
04:25:38,882 --> 04:25:40,984
LOT OF CROSS POLLINATION IN THE

7056
04:25:40,984 --> 04:25:42,385
CABS AND WE'RE TRYING TO ATTRACT

7057
04:25:42,385 --> 04:25:44,254
NEW MEMBERS, YOUNGER MEMBERS,

7058
04:25:44,254 --> 04:25:46,456
MEMBERS OF VARYING IDENTITIES.

7059
04:25:46,456 --> 04:25:48,358
I DO THINK THAT WE HAVE

7060
04:25:48,358 --> 04:25:51,127
BENEFITED BY THE PRESENCE OF TWO

7061
04:25:51,127 --> 04:25:52,929
MDCs IN PHILADELPHIA AND WE'LL

7062
04:25:52,929 --> 04:25:55,031
BE WORKING TO COLLABORATE TO PUT

7063
04:25:55,031 --> 04:25:55,798
SOMETHING TOGETHER WITH THE BEAT

7064
04:25:55,798 --> 04:25:56,199
HIV.

7065
04:25:56,199 --> 04:25:57,634
WE ALSO HAVE FANTASTIC

7066
04:25:57,634 --> 04:25:59,068
LEADERSHIP WITHIN THE CAB, AND

7067
04:25:59,068 --> 04:26:02,505
WE DO HAVE INNOVATIVE IDEAS AND

7068
04:26:02,505 --> 04:26:03,973
RESEARCH SUPPORT THAT'S ALWAYS

7069
04:26:03,973 --> 04:26:05,508
AVAILABLE.

7070
04:26:05,508 --> 04:26:09,379
WE ARE A VERY INTERACTIVE

7071
04:26:09,379 --> 04:26:10,013
RESEARCH TEAM.

7072
04:26:10,013 --> 04:26:11,047
PLANS FOR YEAR THREE.

7073
04:26:11,047 --> 04:26:12,549
THE COMMUNITY HIV CURE RETREAT

7074
04:26:12,549 --> 04:26:14,784
DURING THE SUMMER OF 2024, PLAN

7075
04:26:14,784 --> 04:26:16,586
TO INVITE OTHER MDC MEMBERS IN

7076
04:26:16,586 --> 04:26:17,887
ADDITION TO THE PHILADELPHIA

7077
04:26:17,887 --> 04:26:19,622
COMMUNITY, AS WELL AS EXPAND AND

7078
04:26:19,622 --> 04:26:21,124
DISSEMINATE THE CRISPR FOR CURE

7079
04:26:21,124 --> 04:26:23,893
GLOSSARY OF TERMS.

7080
04:26:23,893 --> 04:26:24,427
THAT'S IT.

7081
04:26:24,427 --> 04:26:29,532
[APPLAUSE]

7082
04:26:29,532 --> 04:26:31,734
>> THANK YOU.

7083
04:26:31,734 --> 04:26:33,169
WE ARE A LITTLE BEHIND BUT WE

7084
04:26:33,169 --> 04:26:35,038
HAVE TIME FOR A FEW QUESTIONS IF

7085
04:26:35,038 --> 04:26:36,873
ANYBODY HAS ANY.

7086
04:26:36,873 --> 04:26:41,377
I HAVE ONE.

7087
04:26:41,377 --> 04:26:42,745
PAULA.

7088
04:26:42,745 --> 04:26:44,781
>> HI.

7089
04:26:44,781 --> 04:26:46,549
I SUPPOSE I WOULD ADDRESS THIS

7090
04:26:46,549 --> 04:26:48,484
TO DR. KHALILLI.

7091
04:26:48,484 --> 04:26:52,655
YOU MENTIONED YOU ARE USING AAVI

7092
04:26:52,655 --> 04:26:55,592
THINK ABOUT AAV9 AS BEING T-CELL

7093
04:26:55,592 --> 04:26:56,759
TROPIC.

7094
04:26:56,759 --> 04:26:59,929
BUT OF COURSE AAV9 GOES INTO

7095
04:26:59,929 --> 04:27:01,364
LIVER, BRAIN, MUSCLE, HEART,

7096
04:27:01,364 --> 04:27:06,502
LUNGS, KIDNEY, PAP K PANCREAS, T

7097
04:27:06,502 --> 04:27:07,937
BASICALLY GOES EVERYWHERE IN THE

7098
04:27:07,937 --> 04:27:09,172
BODY, SO I WONDER IF YOU'RE

7099
04:27:09,172 --> 04:27:10,240
CONCERNED ABOUT THAT OR IF YOU

7100
04:27:10,240 --> 04:27:11,574
HAVE IDEAS TO MAKE MORE TARGETED

7101
04:27:11,574 --> 04:27:14,344
DELIVERY TO T-CELLS.

7102
04:27:14,344 --> 04:27:18,881
>> WE DO -- WE ARE IN
PROCESS OF

7103
04:27:18,881 --> 04:27:23,419
WORKING WITH MIKE FARZAN AND HIS

7104
04:27:23,419 --> 04:27:27,657
GROUP TO IMPROVE THE AAV9 FOR

7105
04:27:27,657 --> 04:27:30,893
TRANSDUCING T-CELLS AND MYELOID

7106
04:27:30,893 --> 04:27:31,861
CELLS, HUMAN AS WELL AS IN THE

7107
04:27:31,861 --> 04:27:32,295
MONKEY.

7108
04:27:32,295 --> 04:27:35,465
SO THAT PROCESS IS GOING ON.

7109
04:27:35,465 --> 04:27:36,799
BUT ONE OF THE THINGS WHICH

7110
04:27:36,799 --> 04:27:38,568
WAS -- WE WERE VERY ENCOURAGED

7111
04:27:38,568 --> 04:27:43,473
WAS IN ANIMAL MODELS, IN SIV AND

7112
04:27:43,473 --> 04:27:44,674
ACTUALLY IN THE MACAQUE AS WELL

7113
04:27:44,674 --> 04:27:46,476
AS IN HUMAN IS MICE.

7114
04:27:46,476 --> 04:27:50,079
WE SAW THAT THE VERY -- IN

7115
04:27:50,079 --> 04:27:52,982
TRANSDUCTION OF THE CD4 CELLS IN

7116
04:27:52,982 --> 04:27:53,483
VIVO.

7117
04:27:53,483 --> 04:27:57,320
WE DON'T SEE STRONG -- IN THE

7118
04:27:57,320 --> 04:27:58,955
CELL CULTURE BUT IT SEEMS

7119
04:27:58,955 --> 04:28:01,057
SOMEHOW THE AAV9 FINDS THE WAY

7120
04:28:01,057 --> 04:28:04,761
TO GET INTO THE CD4 CELLS IN THE

7121
04:28:04,761 --> 04:28:09,966
IIN VIVO CYST TE. WE DON'T KNOW.

7122
04:28:09,966 --> 04:28:10,767
WE DON'T KNOW WHAT THE REASON

7123
04:28:10,767 --> 04:28:13,736
FOR THAT, WHAT CAUSES THE HIGH

7124
04:28:13,736 --> 04:28:15,171
EFFICIENCY IN THE TRANSDUCTION

7125
04:28:15,171 --> 04:28:15,805
IN VIVO BUT IT HAPPENS.

7126
04:28:15,805 --> 04:28:18,141
>> I GUESS IT'S MORE THE
OFF

7127
04:28:18,141 --> 04:28:19,876
TARGET THINGS I WOULD BE KIND OF

7128
04:28:19,876 --> 04:28:21,244
CONCERNED ABOUT OFF TARGET OR

7129
04:28:21,244 --> 04:28:22,111
THE DELUSION EFFECT OF GOING

7130
04:28:22,111 --> 04:28:24,947
INTO SO MANY OTHER TISSUES IN

7131
04:28:24,947 --> 04:28:25,148
VIVO.

7132
04:28:25,148 --> 04:28:27,917
AS YOU KNOW, AAV9 IS USED AS A

7133
04:28:27,917 --> 04:28:29,052
GENE THERAPY VEHICLE TO GO INTO

7134
04:28:29,052 --> 04:28:29,319
MUSCLE.

7135
04:28:29,319 --> 04:28:32,889
SO IT'S REALLY NOT T-CELL TRO 

7136
04:28:32,889 --> 04:28:33,122
TROPIC.

7137
04:28:33,122 --> 04:28:34,991
>> AS I SAID, WE ARE
TRYING TO

7138
04:28:34,991 --> 04:28:38,061
FIND A WAY TO IMPROVE INCREASE

7139
04:28:38,061 --> 04:28:41,064
THE EFFICIENCY OF THE AAV9 IN

7140
04:28:41,064 --> 04:28:46,636
THE -- TO THE -- IT MAY NOT --

7141
04:28:46,636 --> 04:28:47,203
INCREASE EFFICIENCY.

7142
04:28:47,203 --> 04:28:50,573
>> THANK YOU.

7143
04:28:50,573 --> 04:28:55,211
>> EDWARD FROM YOE BEGAN
DA,

7144
04:28:55,211 --> 04:28:56,946
RAKAI AND JOHNS HOPKINS.

7145
04:28:56,946 --> 04:29:02,618
HOW WELL DO THE SINGLE GUIDE RNA

7146
04:29:02,618 --> 04:29:09,826
WORK WITH AAV HIV SUBTYPES?

7147
04:29:09,826 --> 04:29:11,160
>> CAN YOU REPEAT --

7148
04:29:11,160 --> 04:29:16,199
>> THE SVRNAs, ARE THEY
BEST

7149
04:29:16,199 --> 04:29:18,067
ON B SUBTYPE OR MULTIPLE

7150
04:29:18,067 --> 04:29:20,103
SUBTYPES AND RECOMBINANTS?

7151
04:29:20,103 --> 04:29:23,873
HOW WELL DO THEY WORK IN --

7152
04:29:23,873 --> 04:29:25,408
>> RIGHT NOW WE ARE
BASICALLY

7153
04:29:25,408 --> 04:29:28,344
USING THE CLINICAL SAMPLE WHICH

7154
04:29:28,344 --> 04:29:33,683
I THINK -- SUBTYPE B.

7155
04:29:33,683 --> 04:29:35,051
WE HAVEN'T STARTED ANY OTHER

7156
04:29:35,051 --> 04:29:40,423
SUBTYPE.

7157
04:29:40,423 --> 04:29:42,058
>> A COUPLE QUESTIONS.

7158
04:29:42,058 --> 04:29:43,493
ONE IS CAN YOU TALK ABOUT WHAT

7159
04:29:43,493 --> 04:29:45,161
YOUR METHODOLOGY IS FOR LACKING

7160
04:29:45,161 --> 04:29:47,096
FOR CHROMOSOMAL TRANSLOCATIONS

7161
04:29:47,096 --> 04:29:48,231
USING MULTIPLE GUIDES?

7162
04:29:48,231 --> 04:29:48,731
>> YES.

7163
04:29:48,731 --> 04:29:52,068
>> SECOND QUESTION IS, I
THINK

7164
04:29:52,068 --> 04:29:53,936
THE -- ASSAY IS FIND FOR YES/NO

7165
04:29:53,936 --> 04:29:55,271
BUT I'M CURIOUS WHERE YOU STAND

7166
04:29:55,271 --> 04:29:57,140
ON COMING TO MORE QUANTITATIVE

7167
04:29:57,140 --> 04:29:58,975
READOUTS FOR HOW EFFICIENTLY

7168
04:29:58,975 --> 04:30:00,276
YOU'RE EDITING THESE LOCI.

7169
04:30:00,276 --> 04:30:04,347
>> YES, WITH RESPECT TO
THE

7170
04:30:04,347 --> 04:30:05,782
CHROMOSOMAL -- WE STARTED -- WE

7171
04:30:05,782 --> 04:30:08,217
DEVELOPED ACTUALLY THE METHOD

7172
04:30:08,217 --> 04:30:12,388
FOR THE SO-CALLED CAS SEQ FOR

7173
04:30:12,388 --> 04:30:14,924
LOOKING AT THE CHROMOSOMAL

7174
04:30:14,924 --> 04:30:18,060
ARRANGEMENT AS A RESULT OF THE

7175
04:30:18,060 --> 04:30:19,395
EXCISION, LET'S SAY TWO COPIES

7176
04:30:19,395 --> 04:30:20,897
ARE ON TWO DIFFERENT CHROMOSOME

7177
04:30:20,897 --> 04:30:22,298
BUT THEY ARE NOT ELIMINATION OF

7178
04:30:22,298 --> 04:30:26,102
THOSE SEGMENT OF THE PRO -- DNA,

7179
04:30:26,102 --> 04:30:27,703
BRINGS THOSE TWO CHROMOSOMES

7180
04:30:27,703 --> 04:30:29,405
TOGETHER, WHICH IS OBVIOUSLY --

7181
04:30:29,405 --> 04:30:31,374
IT'S A GENOTOXICITY ASSOCIATED

7182
04:30:31,374 --> 04:30:32,708
WITH THE EXCISION.

7183
04:30:32,708 --> 04:30:33,943
WE DIDN'T SEE SOMETHING LIKE

7184
04:30:33,943 --> 04:30:36,679
THAT, BUT WE HAVE ALREADY

7185
04:30:36,679 --> 04:30:37,947
DEVELOPED THE METHOD BASED ON

7186
04:30:37,947 --> 04:30:41,184
THE PUBLISHED STUDIES WAS DONE

7187
04:30:41,184 --> 04:30:42,752
BY OTHERS IN OUR LABORATORY AND

7188
04:30:42,752 --> 04:30:45,221
WE ARE IN PROCESS OF EXAMINING

7189
04:30:45,221 --> 04:30:47,890
THAT ONE.

7190
04:30:47,890 --> 04:30:51,360
SO WHAT WAS YOUR SECOND

7191
04:30:51,360 --> 04:30:51,861
QUESTION?

7192
04:30:51,861 --> 04:30:54,897
OH, EFFICIENCY IS -- WE ARE

7193
04:30:54,897 --> 04:30:58,434
USING A DDPCR TO ASSIST

7194
04:30:58,434 --> 04:31:01,838
EFFICIENCY OF THE EXCISION, OR

7195
04:31:01,838 --> 04:31:03,339
CLEAVAGE OF THE VIRAL DNA.

7196
04:31:03,339 --> 04:31:05,041
>> ONE FINAL QUESTION?

7197
04:31:05,041 --> 04:31:09,645
>> SO ONE COMMENT ANDY
READ FROM

7198
04:31:09,645 --> 04:31:10,146
NIAID.

7199
04:31:10,146 --> 04:31:11,380
I PERSONALLY THINK ANY CURE

7200
04:31:11,380 --> 04:31:12,482
MODALITY IS GOING TO NEED TO

7201
04:31:12,482 --> 04:31:15,685
REQUIRE SOME SORT OF GENE I

7202
04:31:15,685 --> 04:31:17,119
EDITING SO IT'S EXCITING TO SEE

7203
04:31:17,119 --> 04:31:17,854
THAT MOVING FORWARD.

7204
04:31:17,854 --> 04:31:19,755
AND MY QUESTION, THOUGH, IS, FOR

7205
04:31:19,755 --> 04:31:21,324
THE MACAQUE ANALYSIS THAT YOU

7206
04:31:21,324 --> 04:31:22,692
GUYS HAVE DONE WITH YOUR ASSAY,

7207
04:31:22,692 --> 04:31:26,696
YOU KNOW, BOB SILICANO'S PAPER

7208
04:31:26,696 --> 04:31:28,231
SHOWED THE RESERVOIR IN THE

7209
04:31:28,231 --> 04:31:29,131
MACAQUES LOOKS PRETTY DIFFERENT

7210
04:31:29,131 --> 04:31:30,666
THAN WHAT WE SEE IN HUMANS WITH

7211
04:31:30,666 --> 04:31:33,135
A LOT MORE INTACT PROVIRUSES.

7212
04:31:33,135 --> 04:31:34,036
AND ONE QUESTION IS, ARE YOU

7213
04:31:34,036 --> 04:31:35,905
GUYS SEEING THE SAME THING WITH

7214
04:31:35,905 --> 04:31:39,842
YOUR ASSAYS, AND ALSO DO YOU

7215
04:31:39,842 --> 04:31:41,344
KNOW IF ANYONE HAS EVER LOCKED

7216
04:31:41,344 --> 04:31:43,179
IN THINGS LIKE AFRICAN GREEN

7217
04:31:43,179 --> 04:31:44,847
MONKEYS ON THERAPY TO SEE WHAT

7218
04:31:44,847 --> 04:31:46,048
THEIR RESERVOIR LOOKS LIKE?

7219
04:31:46,048 --> 04:31:51,888
AND I'M JUST CURIOUS.

7220
04:31:51,888 --> 04:31:53,656
>> I HAVE VERY LIMITED
DATA ON

7221
04:31:53,656 --> 04:31:54,824
THAT MYSELF, BUT THAT'S

7222
04:31:54,824 --> 04:31:56,125
CERTAINLY SOMETHING THAT WE'LL

7223
04:31:56,125 --> 04:31:56,859
BE LOOKING INTO.

7224
04:31:56,859 --> 04:31:59,095
SO FAR I'VE ONLY TESTED

7225
04:31:59,095 --> 04:32:00,463
BASICALLY ONE MONKEY THAT HAD A

7226
04:32:00,463 --> 04:32:02,164
FAIRLY HIGH VIRAL LOAD AS WELL

7227
04:32:02,164 --> 04:32:04,600
FOR DIFFERENT REASONS.

7228
04:32:04,600 --> 04:32:05,801
WENT OFF THERAPY BRIEFLY.

7229
04:32:05,801 --> 04:32:07,303
SO MAY OVERREPRESENT THE NUMBER

7230
04:32:07,303 --> 04:32:08,804
OF INTACT PROVIRUSES THAT WE'LL

7231
04:32:08,804 --> 04:32:10,139
FIND IN THAT SYSTEM.

7232
04:32:10,139 --> 04:32:11,307
BUT I THINK IT HAS BEEN

7233
04:32:11,307 --> 04:32:13,175
DESCRIBED THAT THERE'S

7234
04:32:13,175 --> 04:32:15,311
COMPLETELY DIFFERENT LANDSCAPE

7235
04:32:15,311 --> 04:32:18,881
OF PERCENT PROVIRUSES IN SIV.

7236
04:32:18,881 --> 04:32:20,316
>> YOU'RE ABSOLUTELY
RIGHT.

7237
04:32:20,316 --> 04:32:22,852
AND SO WE'RE WORKING HERE WITH

7238
04:32:22,852 --> 04:32:26,489
SIV MACK 239M2 WHICH I IS A

7239
04:32:26,489 --> 04:32:27,657
BARCODED VIRUS BUT WE'VE ALSO

7240
04:32:27,657 --> 04:32:29,625
DONE A NUMBER OF STUDIES WITH

7241
04:32:29,625 --> 04:32:30,893
DIFFERENT SHIV VIRUSES AND I

7242
04:32:30,893 --> 04:32:33,462
HAVE A SEPARATE R01 LOOKING AT

7243
04:32:33,462 --> 04:32:38,000
SHIV D WITH KATIE BARR SO WE'RE

7244
04:32:38,000 --> 04:32:39,769
DOING -- TO LOOK AT THE VIRAL

7245
04:32:39,769 --> 04:32:41,070
RESERVOIR.

7246
04:32:41,070 --> 04:32:43,072
SO YEAH.

7247
04:32:43,072 --> 04:32:44,173
>> ALL RIGHT.

7248
04:32:44,173 --> 04:32:51,714
LET'S THANK OUR CRISPR FOR CURE

7249
04:32:51,714 --> 04:32:52,014
SPEAKERS.

7250
04:32:52,014 --> 04:32:53,449
WE HAVE ONE FINAL SESSION COMING

7251
04:32:53,449 --> 04:32:56,886
UP, A PANEL DISCUSSION ABOUT

7252
04:32:56,886 --> 04:32:58,754
EXPANDING HIV CURE RESEARCH

7253
04:32:58,754 --> 04:32:59,655
GLOBALLY.

7254
04:32:59,655 --> 04:33:02,158
WE'RE GOING TO SHORTEN OUR BREAK

7255
04:33:02,158 --> 04:33:04,894
SO THAT WE CAN MAKE SURE

7256
04:33:04,894 --> 04:33:06,429
EVERYBODY HAS A CHANCE TO SEE

7257
04:33:06,429 --> 04:33:08,097
THIS EXCITING PANEL DISCUSSION,

7258
04:33:08,097 --> 04:33:39,940
SO PLEASE COME BACK AT 3:40.
THANKS.

7259
04:33:39,940 --> 04:33:42,209
AND WE AT NIH ALSO ARE VERY

7260
04:33:42,209 --> 04:33:45,879
INTERESTED IN THIS AT NIAID IN

7261
04:33:45,879 --> 04:33:48,448
PARTNERSHIP WITH NIDDK AND NIMH,

7262
04:33:48,448 --> 04:33:49,783
WE'VE PUBLISHED A NOTICE OF

7263
04:33:49,783 --> 04:33:53,720
SPECIAL INTEREST OR NOSI ON HIV

7264
04:33:53,720 --> 04:33:55,388
CURE RELATED RESEARCH IN DIVERSE

7265
04:33:55,388 --> 04:33:55,789
POPULATIONS.

7266
04:33:55,789 --> 04:33:57,724
SO WE'RE TRYING TO ATTRACT MORE

7267
04:33:57,724 --> 04:33:59,092
GRANT APPLICATIONS TO DO HIV

7268
04:33:59,092 --> 04:34:01,695
CURE RESEARCH IN MORE DIVERSE

7269
04:34:01,695 --> 04:34:02,896
POPULATIONS.

7270
04:34:02,896 --> 04:34:03,964
AND SO WE THOUGHT IT WOULD BE

7271
04:34:03,964 --> 04:34:07,167
GREAT TO HAVE A PANEL IN THIS --

7272
04:34:07,167 --> 04:34:09,903
AT THIS MEETING TO DISCUSS WHAT

7273
04:34:09,903 --> 04:34:11,905
REALLY IS NEEDED TO MOVE INTO

7274
04:34:11,905 --> 04:34:18,145
MORE DIVERSE STUDIES IN HIV CURE

7275
04:34:18,145 --> 04:34:18,411
RESEARCH.

7276
04:34:18,411 --> 04:34:19,579
TOM QUINN WILL MODERATE THE

7277
04:34:19,579 --> 04:34:25,418
SESSION.

7278
04:34:25,418 --> 04:34:27,921
>> THANK YOU, KARL, AND
WELCOME

7279
04:34:27,921 --> 04:34:29,656
TO THE FINAL SESSION OF THIS

7280
04:34:29,656 --> 04:34:30,991
FANTASTIC CONFERENCE.

7281
04:34:30,991 --> 04:34:33,393
IN THE PANEL DISCUSSION, WE WANT

7282
04:34:33,393 --> 04:34:37,798
TO HEAR FROM EACH OF THESE YOUNG

7283
04:34:37,798 --> 04:34:40,300
AFRICAN COLLABORATIVE

7284
04:34:40,300 --> 04:34:44,004
INVESTIGATORS AS TO WHAT THE

7285
04:34:44,004 --> 04:34:46,406
SCOPE OF CURE RESEARCH SHOULD BE

7286
04:34:46,406 --> 04:34:48,542
ON THE CONTINENT OF AFRICA, AND

7287
04:34:48,542 --> 04:34:50,577
WE CAN EXPAND TO ASIA, LATIN

7288
04:34:50,577 --> 04:34:52,212
AMERICA AND OTHER PLACES.

7289
04:34:52,212 --> 04:34:55,015
AS KARL JUST MENTIONED, SOME OF

7290
04:34:55,015 --> 04:34:57,350
THE COLLABORATORIES WE'VE HEARD

7291
04:34:57,350 --> 04:35:01,288
FROM ARE ALREADY -- HAVE ALREADY

7292
04:35:01,288 --> 04:35:04,524
NICINITIATED A NUMBER OF STUDIES

7293
04:35:04,524 --> 04:35:05,458
WORKING IN COLLABORATION FROM

7294
04:35:05,458 --> 04:35:06,626
SOME OF THE SCIENTISTS YOU'RE

7295
04:35:06,626 --> 04:35:07,627
ABOUT TO HEAR FROM.

7296
04:35:07,627 --> 04:35:09,596
BUT MORE NEEDS TO BE DONE.

7297
04:35:09,596 --> 04:35:11,665
REMEMBER THERE'S 39 MILLION

7298
04:35:11,665 --> 04:35:15,202
INFECTED PEOPLE IN THE WORLD,

7299
04:35:15,202 --> 04:35:17,904
CLOSE TO 70% RESIDE IN THE

7300
04:35:17,904 --> 04:35:23,176
CONTINENT OF AFRICA.

7301
04:35:23,176 --> 04:35:24,945
CLADE B MAKES UP ONLY A SMALL

7302
04:35:24,945 --> 04:35:30,116
PERCENT OF ALL THE SUBTYPES

7303
04:35:30,116 --> 04:35:31,751
CIRCULATING IN THE WORLD.

7304
04:35:31,751 --> 04:35:34,387
SUBTYPE C MAKES UP FROM 9%.

7305
04:35:34,387 --> 04:35:36,957
HOW MUCH WORK HAS BEEN DONE ON

7306
04:35:36,957 --> 04:35:37,958
SUBTYPE C?

7307
04:35:37,958 --> 04:35:43,697
AND IF YOU GO TO EAST AFRICA,

7308
04:35:43,697 --> 04:35:45,332
AND PARTS OF WEST AFRICA, YOU

7309
04:35:45,332 --> 04:35:52,472
SEE SUBTYPES A, D, REI RECOMBIN,

7310
04:35:52,472 --> 04:35:55,242
ALL OF THE OTHER SUBTYPES ARE

7311
04:35:55,242 --> 04:35:57,210
PRETTY MUCH REPRESENTED IN THAT

7312
04:35:57,210 --> 04:35:57,611
CONTINENT.

7313
04:35:57,611 --> 04:35:59,045
AND YET MOST OF THE WORK AS

7314
04:35:59,045 --> 04:36:02,282
WE'VE HEARD ALL OVER THIS PAST

7315
04:36:02,282 --> 04:36:04,818
TWO DAYS HAS BEEN FOCUSED A LOT,

7316
04:36:04,818 --> 04:36:06,653
AND EXCITING WORK, ON SUBTYPE B.

7317
04:36:06,653 --> 04:36:07,854
AND WHILE THAT'S RELEVANT AND

7318
04:36:07,854 --> 04:36:09,956
WILL PROVIDE US INSIGHT, WE NEED

7319
04:36:09,956 --> 04:36:11,591
TO START THINKING ABOUT

7320
04:36:11,591 --> 04:36:13,493
DIVERSIFYING SOME OF THIS AS TO

7321
04:36:13,493 --> 04:36:18,498
HOW IT CAN BE EFFECTIVE WITH

7322
04:36:18,498 --> 04:36:19,633
OTHER SUBTYPES AND EVALUATING

7323
04:36:19,633 --> 04:36:22,035
THOSE IN AFRICA, IN OTHER AREAS

7324
04:36:22,035 --> 04:36:25,572
OF THE WORLD, SO THAT WE HAVE A

7325
04:36:25,572 --> 04:36:32,345
REAL GLOBAL EFFORT AT HIV CURE.

7326
04:36:32,345 --> 04:36:33,513
SO ASSEMBLED BEFORE YOU ARE

7327
04:36:33,513 --> 04:36:34,481
INDIVIDUALS, SCIENTISTS,

7328
04:36:34,481 --> 04:36:38,285
INVESTIGATORS WHO HAVE REALLY

7329
04:36:38,285 --> 04:36:40,453
BEEN INVOLVED IN THE RESEARCH,

7330
04:36:40,453 --> 04:36:47,093
LEADING TOWARDS CURE.

7331
04:36:47,093 --> 04:36:48,161
THEY'VE COLLABORATED WITH SOME

7332
04:36:48,161 --> 04:36:50,030
OF YOU, THEY'VE SENT SPECIMENS

7333
04:36:50,030 --> 04:36:50,897
ABROAD BACK TO THE U.S.

7334
04:36:50,897 --> 04:36:52,465
SOME OF THE WORK IS STARTING TO

7335
04:36:52,465 --> 04:36:55,635
TAKE PLACE IN AFRICA, AND THAT

7336
04:36:55,635 --> 04:36:57,037
CONTEXT IS EXTREMELY IMPORTANT

7337
04:36:57,037 --> 04:36:59,372
THAT WE START LOOKING AT

7338
04:36:59,372 --> 04:37:00,707
INFRASTRUCTURE, WE START LOOKING

7339
04:37:00,707 --> 04:37:03,143
AT THE SCIENTISTS EDUCATING

7340
04:37:03,143 --> 04:37:05,345
THEM, MENTORING THEM AND HAVING

7341
04:37:05,345 --> 04:37:08,415
THEM PERFORM THE STUDIES WHERE

7342
04:37:08,415 --> 04:37:17,757
THE PARTICIPANTS ARE RESIDING.

7343
04:37:17,757 --> 04:37:19,659
, VERIFY THAT FROM CARL'S

7344
04:37:19,659 --> 04:37:21,227
REMARK, THE INSTITUTE IS VERY

7345
04:37:21,227 --> 04:37:24,698
INTERESTED IN AN INTERNATIONAL

7346
04:37:24,698 --> 04:37:27,100
EFFORT FOR FINDING A CURE FOR

7347
04:37:27,100 --> 04:37:27,467
HIV.

7348
04:37:27,467 --> 04:37:30,303
AND THAT GOES ALL THE WAY FROM

7349
04:37:30,303 --> 04:37:32,305
DAIDS TO THE INTRA MURAL

7350
04:37:32,305 --> 04:37:34,808
PROGRAM, AND I WILL SAY WITH THE

7351
04:37:34,808 --> 04:37:37,577
NEW LEADERSHIP WHO STARTED THIS

7352
04:37:37,577 --> 04:37:47,554
CONFERENCE, DR. GENIE JENANNE.

7353
04:37:47,554 --> 04:37:48,855
SO THIS WILL CLOSE OUT THE

7354
04:37:48,855 --> 04:37:49,956
CONFERENCE AND WE HOPE TO HEAR

7355
04:37:49,956 --> 04:37:51,124
FROM YOU AFTER EACH OF THE

7356
04:37:51,124 --> 04:37:54,294
PANELISTS HAVE GIVEN THER THEIR

7357
04:37:54,294 --> 04:37:55,562
PERSPECTIVE ON WHAT CURE SHOULD

7358
04:37:55,562 --> 04:37:56,796
BE LOOKING LIKE IN AFRICA.

7359
04:37:56,796 --> 04:37:58,531
AND SO I'M GOING TO ASK EACH ONE

7360
04:37:58,531 --> 04:38:04,137
OF THEM TO TAKE THREE, FOUR

7361
04:38:04,137 --> 04:38:05,705
MINUTES, GOING TO HAVE TO KEEP

7362
04:38:05,705 --> 04:38:06,940
IT SHORT BECAUSE WE WANT TO HEAR

7363
04:38:06,940 --> 04:38:08,775
FROM THE AUDIENCE, AND IF IT

7364
04:38:08,775 --> 04:38:09,809
GOES BEYOND FIVE, I'M GOING TO

7365
04:38:09,809 --> 04:38:13,313
HAVE TO CUT YOU OFF, BUT I WILL

7366
04:38:13,313 --> 04:38:15,915
START WITH ZAZA, IF YOU COULD

7367
04:38:15,915 --> 04:38:17,384
INTRODUCE YOURSELF, AND GIVE US

7368
04:38:17,384 --> 04:38:19,986
YOUR PERSPECTIVES ON WHAT NEEDS

7369
04:38:19,986 --> 04:38:23,656
TO BE DONE, WHAT LIES AHEAD IN

7370
04:38:23,656 --> 04:38:25,925
THE FUTURE FOR RESEARCH AND CURE

7371
04:38:25,925 --> 04:38:27,127
IN AFRICA.

7372
04:38:27,127 --> 04:38:29,129
AND PLEASE, AS WE GO DOWN THE

7373
04:38:29,129 --> 04:38:30,764
LINE, JUST GIVE A FULL

7374
04:38:30,764 --> 04:38:34,300
INTRODUCTION, WHAT YOU HAVE BEEN

7375
04:38:34,300 --> 04:38:36,302
DOING IN THIS AREA AND THEN WHAT

7376
04:38:36,302 --> 04:38:37,237
YOUR THOUGHTS ARE FOR THE

7377
04:38:37,237 --> 04:38:39,005
FUTURE.

7378
04:38:39,005 --> 04:38:43,276
THANKS.

7379
04:38:43,276 --> 04:38:44,544
>> ALL RIGHT.

7380
04:38:44,544 --> 04:38:45,812
THANK YOU VERY MUCH.

7381
04:38:45,812 --> 04:38:48,148
AND THANK YOU VERY MUCH FOR THIS

7382
04:38:48,148 --> 04:38:49,649
FANTASTIC OPPORTUNITY TO BE

7383
04:38:49,649 --> 04:38:51,484
INVITED HERE AND TO GIVE

7384
04:38:51,484 --> 04:38:52,652
PERSPECTIVES ABOUT HIV CURE ON

7385
04:38:52,652 --> 04:38:53,653
THE CONTINENT.

7386
04:38:53,653 --> 04:38:57,123
SO MY NAME IS ZAZA NDHLOVU, I'M

7387
04:38:57,123 --> 04:38:58,825
A VIRAL IMMUNOLOGIST BY

7388
04:38:58,825 --> 04:38:59,159
TRAINING.

7389
04:38:59,159 --> 04:39:01,327
I OBTAINED MY PH.D. AT JOHNS

7390
04:39:01,327 --> 04:39:04,097
HOPKINS AND DID MY POSTDOC WITH

7391
04:39:04,097 --> 04:39:06,099
BRUCE AT HARVARD.

7392
04:39:06,099 --> 04:39:08,935
I HAVE MY LAB WITH INTEREST IN

7393
04:39:08,935 --> 04:39:12,472
VIRAL RESERVOIRS IN TISSUES, AND

7394
04:39:12,472 --> 04:39:13,440
IMMUNE RESPONSES, TRYING TO FIND

7395
04:39:13,440 --> 04:39:18,378
WAYS IN WHICH WE CAN PINCH THE

7396
04:39:18,378 --> 04:39:20,113
VIRUS IN THE TISSUES.

7397
04:39:20,113 --> 04:39:23,283
SO RELATED TO HIV CURE RESEARCH

7398
04:39:23,283 --> 04:39:26,152
BEING DONE ON THE CONTINENT,

7399
04:39:26,152 --> 04:39:27,020
PARTICULARLY BASIC SCIENCE

7400
04:39:27,020 --> 04:39:27,887
RESEARCH, INCLUDING

7401
04:39:27,887 --> 04:39:29,522
INTERVENTIONS THAT HAVE ONLY

7402
04:39:29,522 --> 04:39:30,356
BEEN -- INTERVENTIONS THAT HAVE

7403
04:39:30,356 --> 04:39:32,092
BEEN DONE ON THE CONTINENT SO

7404
04:39:32,092 --> 04:39:36,796
FAR, DESPITE BEARING THE BIGGEST

7405
04:39:36,796 --> 04:39:37,197
BURDEN.

7406
04:39:37,197 --> 04:39:39,833
SO VERY FEW AFRICANS THAT ARE

7407
04:39:39,833 --> 04:39:42,735
PIs AND DIRECTLY FUNDED ON THE

7408
04:39:42,735 --> 04:39:44,070
CONTINENT, AND THERE'S VERY

7409
04:39:44,070 --> 04:39:47,140
LIMITED KNOWLEDGE IN THE

7410
04:39:47,140 --> 04:39:47,941
COMMUNITY, INCLUDING THE

7411
04:39:47,941 --> 04:39:49,442
POLITICIANS OR STAKEHOLDERS.

7412
04:39:49,442 --> 04:39:52,479
THE POLITICIANS, PEOPLE LIVING

7413
04:39:52,479 --> 04:39:55,115
WITH HIV, CAREGIVERS KNOW VERY

7414
04:39:55,115 --> 04:39:56,583
LITTLE ABOUT WHAT CURE RESEARCH

7415
04:39:56,583 --> 04:39:58,518
IS, WHAT WE'RE TRYING TO ACHIEVE

7416
04:39:58,518 --> 04:39:59,619
AND WHETHER THEY ARE EVEN PART

7417
04:39:59,619 --> 04:40:00,186
OF THAT.

7418
04:40:00,186 --> 04:40:01,654
SO THE LACK OF OWNERSHIP IS

7419
04:40:01,654 --> 04:40:03,690
REALLY A BIG PROBLEM.

7420
04:40:03,690 --> 04:40:06,059
SO I THINK WHAT WE NEED TO DO IS

7421
04:40:06,059 --> 04:40:09,696
REALLY TO CREATE AN HIV CURE

7422
04:40:09,696 --> 04:40:11,197
RESEARCH ON THE CONTINENT THAT

7423
04:40:11,197 --> 04:40:14,300
IS EQUITABLE AND FAIR AND

7424
04:40:14,300 --> 04:40:15,368
INCLUDES ALL STAKEHOLDERS.

7425
04:40:15,368 --> 04:40:17,704
SO WE NEED TO ENCOURAGE PEOPLE

7426
04:40:17,704 --> 04:40:20,140
IN THE CONTINENT TO WORK WITH

7427
04:40:20,140 --> 04:40:21,875
EACH OTHER, SO WE NEED TO CREATE

7428
04:40:21,875 --> 04:40:23,877
LEADERSHIP ON THE CONTINENT, AND

7429
04:40:23,877 --> 04:40:26,312
THAT LEADERSHIP WILL BE ABLE TO

7430
04:40:26,312 --> 04:40:29,482
SHARE POLICY AND WAYS IN WHICH

7431
04:40:29,482 --> 04:40:31,384
TO CONDUCT CURE RESEARCH IN A

7432
04:40:31,384 --> 04:40:33,419
SAFE AND MEANINGFUL WAY.

7433
04:40:33,419 --> 04:40:35,155
REMEMBER HIV CURE RESEARCH IS

7434
04:40:35,155 --> 04:40:35,488
VERY COMPLEX.

7435
04:40:35,488 --> 04:40:37,524
IF YOU COME TO BASIC SCIENCE,

7436
04:40:37,524 --> 04:40:39,159
YOU NEED LARGE BLOOD VOLUME, WE

7437
04:40:39,159 --> 04:40:40,593
NEED TISSUES OR THESE ARE

7438
04:40:40,593 --> 04:40:41,794
UNUSUAL WAYS OF DOING RESEARCH

7439
04:40:41,794 --> 04:40:43,029
COMPARED TO WHAT WE DID BEFORE.

7440
04:40:43,029 --> 04:40:44,864
SO YOU NEED SPECIAL REGULATION

7441
04:40:44,864 --> 04:40:47,734
AND YOU NEED MORE RESOURCES.

7442
04:40:47,734 --> 04:40:50,270
AND MORE IMPORTANTLY, ON THE

7443
04:40:50,270 --> 04:40:51,504
CONTINENT OF AFRICA FOR THOSE

7444
04:40:51,504 --> 04:40:54,874
THAT ASKED, THE COST OF DOING

7445
04:40:54,874 --> 04:40:57,410
BASIC SCIENCE RESEARCH IS

7446
04:40:57,410 --> 04:40:58,611
EXTREMELY HIGH.

7447
04:40:58,611 --> 04:41:02,448
SO FOR EVERY REAGENT WE GET,

7448
04:41:02,448 --> 04:41:04,751
THAT WOULD COST YOU $100 A YEAR,

7449
04:41:04,751 --> 04:41:06,619
WOULD COST YOU $300 IN AFRICA.

7450
04:41:06,619 --> 04:41:10,256
THE COST OF RUNNING REAGENTS AND

7451
04:41:10,256 --> 04:41:11,491
THE TIME AROUND TO GET THOSE

7452
04:41:11,491 --> 04:41:15,662
REAGENTS ARE VERY EXPENSIVE, AND

7453
04:41:15,662 --> 04:41:16,629
SO EVEN PEOPLE THAT HAVE THE

7454
04:41:16,629 --> 04:41:19,732
IDEAS AND CAN CONDUCT RESEARCH,

7455
04:41:19,732 --> 04:41:20,900
BECAUSE THEY ARE FORCED TO

7456
04:41:20,900 --> 04:41:22,101
COLLABORATE WITH SOMEBODY HERE

7457
04:41:22,101 --> 04:41:23,536
IN THE U.S. OR U.K. AND SHIP

7458
04:41:23,536 --> 04:41:25,104
THEIR SAMPLES, IT'S A LOT

7459
04:41:25,104 --> 04:41:27,073
EASIER, IT'S CHEAPER AND SO WE

7460
04:41:27,073 --> 04:41:29,042
ARE LAGGING BEHIND IN THAT VEIN,

7461
04:41:29,042 --> 04:41:32,245
AND SO WE NEED TO REALLY -- THE

7462
04:41:32,245 --> 04:41:36,916
SOLUTION IS TO FIND AND MOBILIZE

7463
04:41:36,916 --> 04:41:37,317
LEADERSHIP.

7464
04:41:37,317 --> 04:41:38,885
PEOPLE THAT CAN TALK TO THE

7465
04:41:38,885 --> 04:41:40,620
POLITICIANS, PEOPLE THAT CAN

7466
04:41:40,620 --> 04:41:41,721
COMMUNICATE POLICY, PEOPLE THAT

7467
04:41:41,721 --> 04:41:45,592
CAN COME UP WITH A COHERENT

7468
04:41:45,592 --> 04:41:46,759
PROGRAM OF HIV CURE RESEARCH

7469
04:41:46,759 --> 04:41:49,562
THAT IS REALLY TARGETED AT

7470
04:41:49,562 --> 04:41:53,700
ADDRESSING THOSE SUBTYPES THAT

7471
04:41:53,700 --> 04:41:55,902
MOSTLY CIRCULATE ON THE

7472
04:41:55,902 --> 04:41:57,537
CONTINENT.

7473
04:41:57,537 --> 04:41:59,472
>> THANK YOU.

7474
04:41:59,472 --> 04:41:59,806
EDWARD?

7475
04:41:59,806 --> 04:42:09,182
>> TH THANK YOU.

7476
04:42:09,182 --> 04:42:13,186
SO A POSTDOC AT JOHNS HOPKINS IN

7477
04:42:13,186 --> 04:42:24,430
TOM QUINN'S RAB  QUINN'S LAB, W

7478
04:42:25,732 --> 04:42:27,000
UGANDA.

7479
04:42:27,000 --> 04:42:30,003
I WAS THE MOST -- IN THE DAY OF

7480
04:42:30,003 --> 04:42:31,871
THE HIV IN UGANDA, AND WE LOST

7481
04:42:31,871 --> 04:42:35,141
MANY PEOPLE TO HIV.

7482
04:42:35,141 --> 04:42:36,309
FAST FORWARD, MY INTEREST IN

7483
04:42:36,309 --> 04:42:39,746
CURE RESEARCH STARTED AFTER I

7484
04:42:39,746 --> 04:42:41,314
COMPLETED MEDICAL SCHOOL AND

7485
04:42:41,314 --> 04:42:44,484
STARTED PROVIDING CLINICAL CARE

7486
04:42:44,484 --> 04:42:45,618
IN RAKAI.

7487
04:42:45,618 --> 04:42:47,153
THAT'S WHEN I STARTED GETTING

7488
04:42:47,153 --> 04:42:48,454
MULTIPLE DISCLOSURES FROM MANY

7489
04:42:48,454 --> 04:42:50,957
FAMILY MEMBERS ABOUT THEIR

7490
04:42:50,957 --> 04:42:55,461
STATUS AND IF THERE WAS ANY HOPE

7491
04:42:55,461 --> 04:42:58,564
THAT THIS THING COULD GO AWAY.

7492
04:42:58,564 --> 04:42:59,766
SO I STARTED LOOKING FOR

7493
04:42:59,766 --> 04:43:01,401
OPPORTUNITIES AND THAT'S HOW I

7494
04:43:01,401 --> 04:43:03,336
APPLIED TO THE IAS RESEARCH FOR

7495
04:43:03,336 --> 04:43:03,936
CURE ACADEMY AND HAD THE

7496
04:43:03,936 --> 04:43:07,907
OPPORTUNITY TO HAVE SHARON AND

7497
04:43:07,907 --> 04:43:11,778
STEVE AND TUMBE AND -- WHERE IS

7498
04:43:11,778 --> 04:43:13,212
KAREN?

7499
04:43:13,212 --> 04:43:14,881
AND THEM TRAIN US, GIVE US

7500
04:43:14,881 --> 04:43:16,215
REALLY THAT INTRODUCTION WHICH

7501
04:43:16,215 --> 04:43:21,888
WAS MY ENTRY TO THIS FIELD, AND

7502
04:43:21,888 --> 04:43:24,424
SHORTLY AFTER COLLABORATORS OF

7503
04:43:24,424 --> 04:43:28,361
RAKAI, DR. RED, ANDREW, AND

7504
04:43:28,361 --> 04:43:29,095
DR. JESSICA, I THINK THEY'RE

7505
04:43:29,095 --> 04:43:32,799
PROBABLY AROUND.

7506
04:43:32,799 --> 04:43:33,700
ACTUALLY INTRODUCING NEW

7507
04:43:33,700 --> 04:43:35,702
POTENTIAL PROJECT THAT I APPLIED

7508
04:43:35,702 --> 04:43:39,472
FOR AND THAT LED TO MY TRAINING

7509
04:43:39,472 --> 04:43:45,278
IN CANADA, HOW TO ANALYZE THIS,

7510
04:43:45,278 --> 04:43:47,046
AND BIOSTATISTICS AND

7511
04:43:47,046 --> 04:43:49,082
EPIDEMIOLOGY TRAINING.

7512
04:43:49,082 --> 04:43:53,586
SO THIS WAS TO GET THAT KIND OF

7513
04:43:53,586 --> 04:43:54,520
TRAINING.

7514
04:43:54,520 --> 04:43:56,723
EVENTUALLY IT LED TO MY CURRENT

7515
04:43:56,723 --> 04:43:59,359
POSTDOCTORAL FELLOWSHIP.

7516
04:43:59,359 --> 04:44:01,194
AT JOHNS HOPKINS IN TOM QUINN'S

7517
04:44:01,194 --> 04:44:01,427
LAB.

7518
04:44:01,427 --> 04:44:06,566
SO IT BEEN QUITE A JOURNEY FOR

7519
04:44:06,566 --> 04:44:09,035
ME BUT AN INTERESTING ONE.

7520
04:44:09,035 --> 04:44:19,579
NOW, IT IS TEMPTING TO MAKE MANY

7521
04:44:24,517 --> 04:44:30,790
DEMANDS OF YOU, BUT FORGET ABOUT

7522
04:44:30,790 --> 04:44:32,592
ON RESPONSIBILITIES, I THINK I

7523
04:44:32,592 --> 04:44:33,559
WOULD LIKE TO START WITH

7524
04:44:33,559 --> 04:44:33,826
OURSELVES.

7525
04:44:33,826 --> 04:44:35,895
WE HAVE A SAYING, IF YOU POINT

7526
04:44:35,895 --> 04:44:37,330
AT SOMEONE THREE FINGERS ARE

7527
04:44:37,330 --> 04:44:40,099
POINTING BACK AT YOU.

7528
04:44:40,099 --> 04:44:43,369
SO IN OUR OWN CASE, WE HAVE TO

7529
04:44:43,369 --> 04:44:46,072
OWN UP THIS PROBLEM.

7530
04:44:46,072 --> 04:44:48,674
AND THE WORK.

7531
04:44:48,674 --> 04:44:50,176
THE LARGEST BURDEN OF THE

7532
04:44:50,176 --> 04:44:56,749
DISEASE IS ON OUR CONTINENT, BUT

7533
04:44:56,749 --> 04:45:00,520
SOMETIMES WHEN WE'RE IN THIS THE

7534
04:45:00,520 --> 04:45:01,687
COLLABORATIONS, THIS IS A BIT

7535
04:45:01,687 --> 04:45:02,622
EMBARRASSING TO SAY BUT IT HAS

7536
04:45:02,622 --> 04:45:06,125
TO BE SAID, IN SOME CASES WE ARE

7537
04:45:06,125 --> 04:45:08,194
NOT VIEWED AS SERIOUS

7538
04:45:08,194 --> 04:45:10,196
CONTRIBUTORS TO THIS WORK.

7539
04:45:10,196 --> 04:45:15,835
AND SOMETIMES TRULY SO.

7540
04:45:15,835 --> 04:45:17,470
BUT WE HAVE TO MAKE THAT EXTRA

7541
04:45:17,470 --> 04:45:18,805
EFFORT TO PUT IN EXTRA EFFORT

7542
04:45:18,805 --> 04:45:20,406
EVEN WHEN YOU DO NOT HAVE THE

7543
04:45:20,406 --> 04:45:21,040
EXPERTISE, THERE ARE THINGS YOU

7544
04:45:21,040 --> 04:45:22,475
CAN DO FOR YOUR COLLABORATORS TO

7545
04:45:22,475 --> 04:45:24,877
KNOW THAT THIS IS A SERIOUS

7546
04:45:24,877 --> 04:45:30,049
PERSON THAT WE CAN WORK WITH.

7547
04:45:30,049 --> 04:45:33,386
AND SECONDLY, OUR GOVERNMENTS

7548
04:45:33,386 --> 04:45:36,289
ALSO NEED TO DO SOMETHING ABOUT

7549
04:45:36,289 --> 04:45:41,861
THIS.

7550
04:45:41,861 --> 04:45:43,429
IT SAYS IF YOU HAVE SOMEONE CRY

7551
04:45:43,429 --> 04:45:45,198
WITH YOU, THIS IS IN MY TRIBE,

7552
04:45:45,198 --> 04:45:46,399
IF YOU HAVE SOMEONE CRY WITH

7553
04:45:46,399 --> 04:45:50,937
YOU, YOU HAVE TO CRY LOUDER. LON

7554
04:45:50,937 --> 04:45:51,404
THAT PERSON.

7555
04:45:51,404 --> 04:45:55,942
SO WE HAVE GOODWILL OF OUR

7556
04:45:55,942 --> 04:45:57,410
FRIENDS, BUT WHAT ARE WE DOING?

7557
04:45:57,410 --> 04:46:00,146
WE MAY NOT HAVE THE SAME AMOUNT

7558
04:46:00,146 --> 04:46:04,851
OF MONEY, BUT IS THERE SOMETHING

7559
04:46:04,851 --> 04:46:05,918
SMALL THAT WE CAN ACTUALLY

7560
04:46:05,918 --> 04:46:06,752
CONTRIBUTE TO THIS WORK.

7561
04:46:06,752 --> 04:46:10,056
TIME WILL COME FROM FRIENDS ARE

7562
04:46:10,056 --> 04:46:11,257
NOT ABLE TO HELP US.

7563
04:46:11,257 --> 04:46:12,592
MAYBE NOT WITH HIV BUT WITH A

7564
04:46:12,592 --> 04:46:12,992
DIFFERENT PROBLEM.

7565
04:46:12,992 --> 04:46:15,027
IT DID HAPPEN DURING COVID IN

7566
04:46:15,027 --> 04:46:18,931
THE MIDDLE OF THE PANDEMIC.

7567
04:46:18,931 --> 04:46:22,802
EVERYBODY WAS HOLDING VACCINES,

7568
04:46:22,802 --> 04:46:28,341
AND WERE OUT IN THE COLD.

7569
04:46:28,341 --> 04:46:29,909
WHAT DO WE DO IN SUCH IPS

7570
04:46:29,909 --> 04:46:30,243
STANCE?

7571
04:46:30,243 --> 04:46:31,711
SO IN OUR CASE, THE GOVERNMENT

7572
04:46:31,711 --> 04:46:33,913
OF UGANDA DID SOMETHING I'VE

7573
04:46:33,913 --> 04:46:34,847
NEVER SEEN BEFORE.

7574
04:46:34,847 --> 04:46:37,517
I THINK RESEARCH INNOVATION

7575
04:46:37,517 --> 04:46:41,254
FUND, IT WAS I THINK AROUND

7576
04:46:41,254 --> 04:46:44,590
$20,000 PER PERSON THAT THE

7577
04:46:44,590 --> 04:46:47,860
GROUP FUNDED TO HEY, GUYS, DO

7578
04:46:47,860 --> 04:46:48,461
SOMETHING, DO SOMETHING ABOUT

7579
04:46:48,461 --> 04:46:48,928
THIS THING.

7580
04:46:48,928 --> 04:46:50,763
NOW WE DON'T NEED TO WAIT FOR

7581
04:46:50,763 --> 04:46:55,434
TOUGH TIMES LIKE THAT TO COME.

7582
04:46:55,434 --> 04:46:56,969
WE NEED TO ACTUALLY START DOING

7583
04:46:56,969 --> 04:46:58,905
THESE THINGS AS AFRICAN PEOPLE,

7584
04:46:58,905 --> 04:47:01,173
AS PEOPLE IN OTHER LMICs SO

7585
04:47:01,173 --> 04:47:03,576
THAT IN CASE WE ARE IN SUCH A

7586
04:47:03,576 --> 04:47:05,077
SITUATION EVER AGAIN, WE'RE ABLE

7587
04:47:05,077 --> 04:47:08,014
TO DO SOMETHING ON OUR OWN.

7588
04:47:08,014 --> 04:47:09,448
SHOULD I PAUSE THERE?

7589
04:47:09,448 --> 04:47:09,682
>> YES.

7590
04:47:09,682 --> 04:47:10,516
>> THANK YOU.

7591
04:47:10,516 --> 04:47:14,620
>> WE'LL BE ABLE TO COME
BACK

7592
04:47:14,620 --> 04:47:16,856
AFTERWARDS.

7593
04:47:16,856 --> 04:47:25,765
IMMACULATE?

7594
04:47:25,765 --> 04:47:27,300
>> GOOD AFTERNOON,
EVERYONE.

7595
04:47:27,300 --> 04:47:30,970
MY NAME IS IMMACULATE NANKYA.

7596
04:47:30,970 --> 04:47:33,139
I'M BASED IN UGANDA AT THE JOINT

7597
04:47:33,139 --> 04:47:36,876
CLINICAL RESEARCH CENTRE,

7598
04:47:36,876 --> 04:47:39,211
CO-DIRECTOR OF THE RUST BUILD

7599
04:47:39,211 --> 04:47:40,246
SAFER, COLAB RANGE OF MOTION

7600
04:47:40,246 --> 04:47:41,681
BETWEEN THE UNIVERSITY AND

7601
04:47:41,681 --> 04:47:42,615
UNIVERSITY OF PITTSBURGH, SO I

7602
04:47:42,615 --> 04:47:51,290
WORK IN COLLABORATION WITH JOHN

7603
04:47:51,290 --> 04:47:55,227
I'M A MOLECULAR BIOLOGIST, I'M A

7604
04:47:55,227 --> 04:47:57,997
MEDICAL BIOLOGIST VIROLOGIST

7605
04:47:57,997 --> 04:47:58,931
BASICALLY, AND BASICALLY I WAS

7606
04:47:58,931 --> 04:48:02,101
IN THE HIV RESISTANCE AND THEN

7607
04:48:02,101 --> 04:48:06,572
MOVED INTO HIV CURE WITH THE

7608
04:48:06,572 --> 04:48:08,040
PEOPLE HAVE MENTIONED, AND THE

7609
04:48:08,040 --> 04:48:11,777
ISSUE AT HAND CURRENTLY IS YES

7610
04:48:11,777 --> 04:48:13,212
THERE IS A LOT OF WORK THAT HAS

7611
04:48:13,212 --> 04:48:17,717
BEEN DONE IN THE SUBTYPE B, AND

7612
04:48:17,717 --> 04:48:19,652
THESE ARE PREDOMINANTLY MALE

7613
04:48:19,652 --> 04:48:21,320
COHORT, SO THERE IS A NEED TO

7614
04:48:21,320 --> 04:48:24,190
DIVERSIFY TO LOOK AT WHAT IS OUT

7615
04:48:24,190 --> 04:48:29,195
THERE, WHAT IS MAINLY IN AFRICA,

7616
04:48:29,195 --> 04:48:31,964
THEY ARE MORE PREDOMINANTLY

7617
04:48:31,964 --> 04:48:33,199
FEMALE, HETEROSEXUAL COMMUNITY,

7618
04:48:33,199 --> 04:48:38,471
THEY ARE MORE DIVERSE

7619
04:48:38,471 --> 04:48:40,239
POPULATIONS AND DIVERSE

7620
04:48:40,239 --> 04:48:41,440
SUBTYPES, AS YOU KNOW MOST OF

7621
04:48:41,440 --> 04:48:43,209
THE SUBTYPES IN AFRICA, AND

7622
04:48:43,209 --> 04:48:46,946
PRECISELY IN UGANDA, WE HAVE

7623
04:48:46,946 --> 04:48:49,949
SUBTYPE A, D, C, AND THEN THE

7624
04:48:49,949 --> 04:48:51,317
RECOMBINANTS.

7625
04:48:51,317 --> 04:48:54,920
SO -- AND AS WE ALL KNOW THAT

7626
04:48:54,920 --> 04:48:56,155
ALREADY MUCH OF THE WORK IS DONE

7627
04:48:56,155 --> 04:48:57,590
IN SUBTYPE B AND THERE IS NEED

7628
04:48:57,590 --> 04:49:00,860
TO OPTIMIZE SO THE KEY THING

7629
04:49:00,860 --> 04:49:02,895
HERE IS TO OPTIMIZE ASSAYS FROM

7630
04:49:02,895 --> 04:49:06,699
THE B TO THE NON-Bs.

7631
04:49:06,699 --> 04:49:11,804
AND ALSO RIGHT NOW WE'RE DOING

7632
04:49:11,804 --> 04:49:12,705
THAT KIND OF WORK.

7633
04:49:12,705 --> 04:49:16,976
BECAUSE I WORK IN COLLABORATION

7634
04:49:16,976 --> 04:49:18,944
WITH THIS HERE, SO OPTIMIZATION

7635
04:49:18,944 --> 04:49:21,213
ALSO BRINGS ALONG TRAINING, SO

7636
04:49:21,213 --> 04:49:22,815
WE HAVE PEOPLE COMING FROM

7637
04:49:22,815 --> 04:49:27,653
UGANDA TO COME HERE IN THE U.S.

7638
04:49:27,653 --> 04:49:29,388
AND THEY'RE TRAINED IN THE

7639
04:49:29,388 --> 04:49:30,723
OPTIMIZATION, GAINING ALSO THE

7640
04:49:30,723 --> 04:49:30,990
EXPERTISE.

7641
04:49:30,990 --> 04:49:32,124
AND THIS IS VERY CRUCIAL BECAUSE

7642
04:49:32,124 --> 04:49:33,292
YOU CAN'T DO THIS WORK WHEN YOU

7643
04:49:33,292 --> 04:49:34,527
DON'T HAVE THE EXPERTISE.

7644
04:49:34,527 --> 04:49:36,095
SO ONCE THESE PEOPLE ARE

7645
04:49:36,095 --> 04:49:38,030
TRAINED, THEN ALSO THERE IS NEED

7646
04:49:38,030 --> 04:49:40,366
TO -- THIS IS CAPACITY BUILDING,

7647
04:49:40,366 --> 04:49:41,934
SO THE CAPACITY BUILDING THEN

7648
04:49:41,934 --> 04:49:44,036
NOW MEANS THAT THERE IS ALSO

7649
04:49:44,036 --> 04:49:45,237
TECHNOLOGY TRANSFER, SO

7650
04:49:45,237 --> 04:49:46,539
BASICALLY IN THIS KIND OF WORK,

7651
04:49:46,539 --> 04:49:50,309
WE REALLY NEED TO BUILD THAT

7652
04:49:50,309 --> 04:49:51,644
CAPACITY TO DO THIS WORK, SO

7653
04:49:51,644 --> 04:49:56,115
THAT WE CAN CLEARLY UNDERSTAND

7654
04:49:56,115 --> 04:49:59,685
WHAT WE HAVE, THE RESEARCH WE'RE

7655
04:49:59,685 --> 04:50:01,420
DOING RIGHT NOW IS STILL AT --

7656
04:50:01,420 --> 04:50:04,590
WE ARE TRYING TO UNDERSTAND THE

7657
04:50:04,590 --> 04:50:07,059
ACTUAL DYNAMICS OF THE RESERVOIR

7658
04:50:07,059 --> 04:50:09,361
IN THE NON-Bs AND IT NEEDS A

7659
04:50:09,361 --> 04:50:10,563
LITTLE CHARACTERIZATION, IS

7660
04:50:10,563 --> 04:50:12,198
NEEDS A LOT OF -- ALL THESE

7661
04:50:12,198 --> 04:50:13,799
ASSAYS, BUT ALSO THE ASSAYS COME

7662
04:50:13,799 --> 04:50:18,337
WITH EQUIPMENT, SO WE FIND THAT

7663
04:50:18,337 --> 04:50:22,575
IN THIS -- OUR COUNTRIES, MOST

7664
04:50:22,575 --> 04:50:24,076
OF IT IS NOT AVAILABLE.

7665
04:50:24,076 --> 04:50:25,177
FOR MOST OF THE WORK WE HAVE

7666
04:50:25,177 --> 04:50:26,579
DONE PREVIOUSLY, WE HAVE BEEN

7667
04:50:26,579 --> 04:50:28,314
DOING SOME PART OF THE WORK IN

7668
04:50:28,314 --> 04:50:30,850
OUR COUNTRIES LIKE IN UGANDA,

7669
04:50:30,850 --> 04:50:32,785
AND THEN SHIP THE SAMPLES TO

7670
04:50:32,785 --> 04:50:33,319
HERE.

7671
04:50:33,319 --> 04:50:37,123
SO THAT THE LAST PART OF THE

7672
04:50:37,123 --> 04:50:38,424
ASSAYS, THE MEASUREMENT ASSAYS

7673
04:50:38,424 --> 04:50:39,291
ARE DONE HERE.

7674
04:50:39,291 --> 04:50:42,795
SO WE WILL NOT BE ABLE TO REALLY

7675
04:50:42,795 --> 04:50:45,164
SUCCESSFULLY DO THIS WORK WHEN

7676
04:50:45,164 --> 04:50:47,800
WE DON'T HAVE THE EQUIPMENT.

7677
04:50:47,800 --> 04:50:49,568
THEN ONCE WE HAVE -- WE MAY NOT

7678
04:50:49,568 --> 04:50:52,238
BE -- I MAY NOT HAVE ALL THE

7679
04:50:52,238 --> 04:50:53,773
EQUIPMENT, I MAY NOT HAVE THE

7680
04:50:53,773 --> 04:50:56,008
DROPLET PCR AND THEN THE

7681
04:50:56,008 --> 04:50:57,243
NANOPOLE AND ALL THESE THINGS,

7682
04:50:57,243 --> 04:51:00,980
BUT AS MAYBE COLLABORATIONS ARE

7683
04:51:00,980 --> 04:51:01,914
REALLY VERY IMPORTANT FOR US, SO

7684
04:51:01,914 --> 04:51:03,682
IF WE CAN ALSO -- LIKE WE DO THE

7685
04:51:03,682 --> 04:51:05,050
NORTH TO SOUTH COLLABORATIONS,

7686
04:51:05,050 --> 04:51:07,219
IT ALSO IMPORTANT WITHIN

7687
04:51:07,219 --> 04:51:09,255
COUNTRY, WITHIN THE AFRICAN

7688
04:51:09,255 --> 04:51:13,259
CONTINENT TO HAVE

7689
04:51:13,259 --> 04:51:13,759
COLLABORATIONS.

7690
04:51:13,759 --> 04:51:14,860
SOMETIMES YOU TEND THAT WE FIND

7691
04:51:14,860 --> 04:51:16,262
TO KEEP OR YOU KNOW LIKE YOU

7692
04:51:16,262 --> 04:51:17,296
HIDE YOUR EQUIPMENT, YOU DON'T

7693
04:51:17,296 --> 04:51:21,066
WANT TO SHARE IT WITH SOMEONE

7694
04:51:21,066 --> 04:51:22,835
ELSE, AND THAT ALSO HINDERS OUR

7695
04:51:22,835 --> 04:51:23,669
PROGRESS IN RESEARCH.

7696
04:51:23,669 --> 04:51:25,571
SO REALLY I'D ADVOCATE FOR US TO

7697
04:51:25,571 --> 04:51:26,772
BE MORE OPEN TO COLLABORATIONS.

7698
04:51:26,772 --> 04:51:27,907
SOMETIMES WHEN I HAVE AN IDEA,

7699
04:51:27,907 --> 04:51:29,408
SOMEONE ELSE WILL NOT TAKE IT UP

7700
04:51:29,408 --> 04:51:30,576
BECAUSE THEY DON'T WANT TO WORK

7701
04:51:30,576 --> 04:51:32,011
WITH ME, THEY WOULD PREFER TO

7702
04:51:32,011 --> 04:51:33,779
WORK WITH SOMEONE IN THE NORTH

7703
04:51:33,779 --> 04:51:35,414
THAN SOMEONE IN THE SOUTH.

7704
04:51:35,414 --> 04:51:37,983
SO IT'S REALLY IMPORTANT AS WE

7705
04:51:37,983 --> 04:51:41,921
GO INTO THIS, NOT THAT -- SOUTH

7706
04:51:41,921 --> 04:51:45,057
TO SOUTH, WITHIN CO COUNTRY, WIN

7707
04:51:45,057 --> 04:51:47,560
THE CONTINENT IS IMPORTANT IF WE

7708
04:51:47,560 --> 04:51:49,195
ARE TO GO FARTHER IN THE CURE

7709
04:51:49,195 --> 04:51:49,428
AGENDA.

7710
04:51:49,428 --> 04:51:49,895
THANK YOU VERY MUCH.

7711
04:51:49,895 --> 04:51:54,934
>> THANK YOU, IMMA
IMMACULATE.

7712
04:51:54,934 --> 04:51:55,634
JULIE?

7713
04:51:55,634 --> 04:51:57,770
>> I'M JULIE AKE, DIRECTOR
OF

7714
04:51:57,770 --> 04:52:00,606
THE U.S. MILITARY HIV RESEARCH

7715
04:52:00,606 --> 04:52:01,807
PROGRAM.

7716
04:52:01,807 --> 04:52:07,880
WHICH MEANS I WORK IN KENYA AND

7717
04:52:07,880 --> 04:52:15,221
UGANDA AND IN TANZANIA, AND

7718
04:52:15,221 --> 04:52:22,127
TIAMU IN NIGERIA AS WELL AS

7719
04:52:22,127 --> 04:52:24,997
DR. SORCHI, IN THAILAND AND

7720
04:52:24,997 --> 04:52:25,898
INCREASINGLY WORKING IN THE

7721
04:52:25,898 --> 04:52:26,432
PHILIPPINES.

7722
04:52:26,432 --> 04:52:27,633
I'VE LEARNED MORE FROM THOSE

7723
04:52:27,633 --> 04:52:28,934
INDIVIDUALS IN THE COURSE OF MY

7724
04:52:28,934 --> 04:52:33,205
LIFE AND MY CAREER REALLY THAN

7725
04:52:33,205 --> 04:52:34,707
ANY OF THE TERRIFIC MENTORS I'VE

7726
04:52:34,707 --> 04:52:36,275
HAD HERE IN THE STATES, BECAUSE

7727
04:52:36,275 --> 04:52:38,644
OF THE REALLY OUTSTANDING WORK

7728
04:52:38,644 --> 04:52:40,913
THAT THEY DO IN THEIR LOCAL

7729
04:52:40,913 --> 04:52:42,181
COMMUNITIES, AND WE ALL LEARN

7730
04:52:42,181 --> 04:52:43,983
HOW TO DO CLINICAL TRIALS RIGHT

7731
04:52:43,983 --> 04:52:47,186
FROM THESE EXPERTS IN LOW AND

7732
04:52:47,186 --> 04:52:48,621
MIDDLE INCOME SETTINGS.

7733
04:52:48,621 --> 04:52:52,224
I WOULD ADD, AT MHRP, WE ALWAYS

7734
04:52:52,224 --> 04:52:53,826
DO THE BULK OF OUR RESEARCH

7735
04:52:53,826 --> 04:52:54,226
INTERNATIONALLY.

7736
04:52:54,226 --> 04:52:55,694
IT HOW I GREW UP.

7737
04:52:55,694 --> 04:52:57,596
I'VE ALWAYS SEEN THAT THE

7738
04:52:57,596 --> 04:53:00,332
POSSIBLE IS ALWAYS THERE IN

7739
04:53:00,332 --> 04:53:02,768
INTERNATIONAL SETTINGS.

7740
04:53:02,768 --> 04:53:04,436
PROBABLY CONDUCTED IN MY

7741
04:53:04,436 --> 04:53:07,039
EXPERIENCE, OFTEN BETTER.

7742
04:53:07,039 --> 04:53:08,741
AND SO WE SHOULD ALWAYS EXPECT

7743
04:53:08,741 --> 04:53:09,508
MORE.

7744
04:53:09,508 --> 04:53:11,143
GO FORTH BOLDLY IN THIS AREA AND

7745
04:53:11,143 --> 04:53:11,911
EXPECT SUCCESS.

7746
04:53:11,911 --> 04:53:15,881
WE'VE ONLY EVER SEEN IT IN TERMS

7747
04:53:15,881 --> 04:53:18,250
OF BEING ABLE TO OPERATIONALIZE

7748
04:53:18,250 --> 04:53:19,551
VERY COMPLEX STUDIES IN THESE

7749
04:53:19,551 --> 04:53:20,052
SETTINGS.

7750
04:53:20,052 --> 04:53:21,720
IT GIVES ME A HUGE AMOUNT OF

7751
04:53:21,720 --> 04:53:28,127
CONFIDENCE IN TERMS OF THE

7752
04:53:28,127 --> 04:53:29,061
DIRECTION THAT THE FIELD IS

7753
04:53:29,061 --> 04:53:29,662
TAKING.

7754
04:53:29,662 --> 04:53:30,930
I'LL SHARE MY OWN EXPERIENCE,

7755
04:53:30,930 --> 04:53:32,464
WE'VE ALWAYS DONE A LOT OF

7756
04:53:32,464 --> 04:53:33,399
VACCINE WORK INTERNATIONALLY,

7757
04:53:33,399 --> 04:53:35,935
BUT MORE RECENTLY, COMPLETED A

7758
04:53:35,935 --> 04:53:40,005
STUDY WHERE WE GAVE VRC01 DURING

7759
04:53:40,005 --> 04:53:43,575
ACUTE INFECTION SO OFTEN WITHIN

7760
04:53:43,575 --> 04:53:46,946
21 DAYS OF A NEGATIVE TEST IN

7761
04:53:46,946 --> 04:53:49,515
UGANDA, KENYA, TANZANIA AND

7762
04:53:49,515 --> 04:53:52,885
THAILAND ADMINISTERING

7763
04:53:52,885 --> 04:53:53,652
VRC01 OBVIOUSLY UNDERGOING

7764
04:53:53,652 --> 04:53:54,753
INFORMED CONSENT, THE SITES AND

7765
04:53:54,753 --> 04:53:56,922
THE LOCAL INVESTIGATORS ALSO

7766
04:53:56,922 --> 04:54:00,526
WERE ABLE TO TRAIN UP AND

7767
04:54:00,526 --> 04:54:02,828
PERFORM A NUMBER OF TISSUE

7768
04:54:02,828 --> 04:54:08,901
SAMPLING PREA DEURS.

7769
04:54:08,901 --> 04:54:10,336
THE LOCAL CLINICIANS, THEY SAY

7770
04:54:10,336 --> 04:54:11,971
SURE, YOU CAN TRAIN ME TO DO A

7771
04:54:11,971 --> 04:54:14,273
LYMPH NODE BIOPSY, I'M ALREADY

7772
04:54:14,273 --> 04:54:15,307
CREDENTIALED.

7773
04:54:15,307 --> 04:54:16,508
THEY CAN ALSO TAKE OUT MY

7774
04:54:16,508 --> 04:54:17,643
APPENDIX AND DELIVER MY BABY,

7775
04:54:17,643 --> 04:54:17,843
RIGHT?

7776
04:54:17,843 --> 04:54:19,545
I MEAN, WE SHOULD NEVER

7777
04:54:19,545 --> 04:54:22,114
UNDERESTIMATE WHAT IS CAPABLE IN

7778
04:54:22,114 --> 04:54:24,883
THAT SETTING, BUT THEY ALSO,

7779
04:54:24,883 --> 04:54:30,222
WITH THE GUT BIOPSIES THEY

7780
04:54:30,222 --> 04:54:31,757
CAPABLY PERFORMED, GENERATED

7781
04:54:31,757 --> 04:54:32,891
REALLY IMPORTANT DATA ON THE

7782
04:54:32,891 --> 04:54:37,663
PRESENCE OF VRC01 AND I'M GOI

7783
04:54:37,663 --> 04:54:38,964
GOING -- AMINO INFLAMMATORY

7784
04:54:38,964 --> 04:54:41,800
MARKEMARKERS, THEY DID AN OUTSTG

7785
04:54:41,800 --> 04:54:43,535
JOB SO I'M EXCITED WE HAVE AN

7786
04:54:43,535 --> 04:54:44,670
OPPORTUNITY TO REALLY SORT OF

7787
04:54:44,670 --> 04:54:47,106
STEP ON THE GAS FOR WORKING IN

7788
04:54:47,106 --> 04:54:48,407
INTERNATIONAL POPULATIONS AND

7789
04:54:48,407 --> 04:54:52,144
WITH THE SUPPORT THAT NIAID IS

7790
04:54:52,144 --> 04:54:55,748
INCREASINGLY PROVIDING WITH OUR

7791
04:54:55,748 --> 04:54:57,049
PARTNERS THAT I'VE MENTIONED,

7792
04:54:57,049 --> 04:54:59,852
ALSO WITH COLLEAGUES IN THE

7793
04:54:59,852 --> 04:55:01,186
PHILIPPINES, WE'RE LAUNCHING AN

7794
04:55:01,186 --> 04:55:02,388
INITIATIVE WE CALL DELIVER,

7795
04:55:02,388 --> 04:55:05,124
WHICH IS DEVELOPING LEADERSHIP

7796
04:55:05,124 --> 04:55:07,059
AND INNOVATION IN VIRAL

7797
04:55:07,059 --> 04:55:11,296
ERADICATION RESEARCH, REALLY

7798
04:55:11,296 --> 04:55:16,902
WITH AN AIM TOWARDS DOING MORE

7799
04:55:16,902 --> 04:55:19,671
MULTISITE IMPACTFUL CURE TRIALS,

7800
04:55:19,671 --> 04:55:22,374
CAPITALIZING ON THE ABILITY TO

7801
04:55:22,374 --> 04:55:25,778
INTERVENE AT THE TIME OF HIV

7802
04:55:25,778 --> 04:55:30,916
DIAGNOSIS, AND CHALLENGING

7803
04:55:30,916 --> 04:55:32,785
OURSELVES TO SEE IF -- NOT JUST

7804
04:55:32,785 --> 04:55:34,486
THROUGH THE COHORTS WE'VE BEEN

7805
04:55:34,486 --> 04:55:35,621
WORKING ON FOR YEARS BUT THROUGH

7806
04:55:35,621 --> 04:55:37,923
OUR PEPFAR PROGRAM PLATFORM, CAN

7807
04:55:37,923 --> 04:55:39,558
WE REALLY INTEGRATE WITH PUBLIC

7808
04:55:39,558 --> 04:55:45,230
HEALTH CASE FINDING STRATEGIES

7809
04:55:45,230 --> 04:55:46,532
TO WORK WITH THESE POPULATIONS

7810
04:55:46,532 --> 04:55:47,633
AND START TO DELIVER TRIALS TO

7811
04:55:47,633 --> 04:55:50,903
THE POPULATIONS GLOBALLY AS

7812
04:55:50,903 --> 04:55:52,871
THESE DIAGNOSES ARE BEING MADE.

7813
04:55:52,871 --> 04:55:53,872
REALLY EXCITED ABOUT THIS

7814
04:55:53,872 --> 04:55:54,306
EFFORT.

7815
04:55:54,306 --> 04:55:57,476
THAT'S WHAT WE'RE ALL HO HERE F,

7816
04:55:57,476 --> 04:55:57,743
ISN'T IT?

7817
04:55:57,743 --> 04:55:58,110
THANK YOU.

7818
04:55:58,110 --> 04:56:01,180
>> THANKS, JULIE.

7819
04:56:01,180 --> 04:56:04,016
AND NEXT IS HANEEFA, WHO WILL

7820
04:56:04,016 --> 04:56:05,250
FILL US IN ON SOME OF THESE

7821
04:56:05,250 --> 04:56:08,020
OPPORTUNITIES.

7822
04:56:08,020 --> 04:56:08,720
>> THANKS.

7823
04:56:08,720 --> 04:56:11,757
I'M REALLY EXCITED TO BE HERE.

7824
04:56:11,757 --> 04:56:17,863
MY NAME IS HANEEFA SALEEM, JOHNS

7825
04:56:17,863 --> 04:56:19,031
HOPKINS BLOOMBERG SCHOOL OF

7826
04:56:19,031 --> 04:56:19,364
PUBLIC HEALTH.

7827
04:56:19,364 --> 04:56:20,332
ONE OF THE ROLES THAT I ALSO

7828
04:56:20,332 --> 04:56:24,236
HOLD IS DIRECTOR OF THE INTERC

7829
04:56:24,236 --> 04:56:25,104
SUB-SAHARAN AFRICA WORKING

7830
04:56:25,104 --> 04:56:27,106
DWREUP AND I'M ALSO THE PROGRAM

7831
04:56:27,106 --> 04:56:28,307
LEAD FOR A NEW INITIATIVE THAT

7832
04:56:28,307 --> 04:56:33,145
WE JUST LAUNCHED, NIH FUNDED

7833
04:56:33,145 --> 04:56:34,947
CFAR AFRICURE PROGRAM.

7834
04:56:34,947 --> 04:56:36,682
WE'VE HEARD OF THE NEED TO

7835
04:56:36,682 --> 04:56:37,850
DIVERSIFY CURE RESEARCH AND PART

7836
04:56:37,850 --> 04:56:39,918
OF THAT IS DIVERSIFYING THE

7837
04:56:39,918 --> 04:56:40,185
WORKFORCE.

7838
04:56:40,185 --> 04:56:45,157
SO THE CFAR AFRICARE PROGRAM IS

7839
04:56:45,157 --> 04:56:46,892
INTENDED TO ADVANCE HIV CURE

7840
04:56:46,892 --> 04:56:48,127
RESEARCH IN AFRICA IN PARTICULAR

7841
04:56:48,127 --> 04:56:50,829
BY PROVIDING MENTOR

7842
04:56:50,829 --> 04:56:55,267
DEVELOPMENTAL AWARDS TO

7843
04:56:55,267 --> 04:56:56,502
INVESTIGATORS BASED IN AFRICA

7844
04:56:56,502 --> 04:56:58,704
WHO CAN ADDRESS SOME OF THE

7845
04:56:58,704 --> 04:56:59,638
ISSUES SPECIFIC FOR AFRICA.

7846
04:56:59,638 --> 04:57:01,173
THROUGH THIS PROGRAM, WE'RE

7847
04:57:01,173 --> 04:57:04,343
AIMING TO PROVIDE SMALL DEVEL

7848
04:57:04,343 --> 04:57:05,544
DEVELOPMENT AWARDS REALLY TO

7849
04:57:05,544 --> 04:57:06,945
INVEST IN THE PEOPLE WHO

7850
04:57:06,945 --> 04:57:08,680
HOPEFULLY WILL DO THIS WORK.

7851
04:57:08,680 --> 04:57:13,085
WE HEARD FROM SOME OF OUR OTHER

7852
04:57:13,085 --> 04:57:13,819
COLLEAGUES ON THE PANEL IN TERMS

7853
04:57:13,819 --> 04:57:15,654
OF THE NEED FOR INDEPENDENT

7854
04:57:15,654 --> 04:57:16,622
INVESTIGATORS IN AFRICA DOING

7855
04:57:16,622 --> 04:57:21,593
THIS TYPE OF WORK, SO WE'RE

7856
04:57:21,593 --> 04:57:22,995
REALLY TRYING TO PUSH FOR THAT

7857
04:57:22,995 --> 04:57:24,163
BY BUILDING CAPACITY LOCALLY.

7858
04:57:24,163 --> 04:57:26,365
THERE ARE SEVERAL ELEMENTS OF

7859
04:57:26,365 --> 04:57:26,932
THE PROGRAM.

7860
04:57:26,932 --> 04:57:28,000
FIRST THERE'S OBVIOUSLY THE

7861
04:57:28,000 --> 04:57:29,468
AWARD, BUT MORE IMPORTANTLY

7862
04:57:29,468 --> 04:57:34,640
THERE'S THE MENTORSHIP, SO

7863
04:57:34,640 --> 04:57:36,275
AWARDEES WILL BE MENTORED BY

7864
04:57:36,275 --> 04:57:38,210
SENIOR INVESTIGATORS ACROSS THE

7865
04:57:38,210 --> 04:57:39,745
CFARs, BUT THEN THERE ARE ALSO

7866
04:57:39,745 --> 04:57:41,480
LOCAL INVESTIGATORS IN AFRICA

7867
04:57:41,480 --> 04:57:42,714
WHO ARE DOING THIS WORK AND PART

7868
04:57:42,714 --> 04:57:44,850
OF THAT IS TO BUILD WHAT

7869
04:57:44,850 --> 04:57:46,051
IMMACULATE MENTIONED, SOME OF

7870
04:57:46,051 --> 04:57:47,586
THESE REGIONAL COLLABORATIONS

7871
04:57:47,586 --> 04:57:50,289
AND COLLABORATIONS WITHIN THE

7872
04:57:50,289 --> 04:57:52,090
CONTINENT.

7873
04:57:52,090 --> 04:57:54,026
SO WE'RE REALLY EXCITED ABOUT

7874
04:57:54,026 --> 04:57:54,526
THIS PROGRAM.

7875
04:57:54,526 --> 04:57:57,296
WE HAD A FLYER THAT WAS UP

7876
04:57:57,296 --> 04:57:59,364
EARLIER, BUT I'M HAPPY TO TALK

7877
04:57:59,364 --> 04:58:01,533
MORE ABOUT THIS PROGRAM, AND

7878
04:58:01,533 --> 04:58:04,102
WE'RE HOPING -- WE'RE LOOKING

7879
04:58:04,102 --> 04:58:05,070
FORWARD TO RECEIVING APPLICANTS

7880
04:58:05,070 --> 04:58:06,505
AND REALLY LAUNCHING THIS

7881
04:58:06,505 --> 04:58:10,242
PROGRAM, AND I WANT TO ENCOURAGE

7882
04:58:10,242 --> 04:58:11,610
ALL OF YOU WHO MAY BE WORKING

7883
04:58:11,610 --> 04:58:14,479
WITH INVESTIGATORS, MAY HAVE

7884
04:58:14,479 --> 04:58:15,781
COLLEAGUES IN AFRICA TO SPREAD

7885
04:58:15,781 --> 04:58:17,950
THE WORD OF THIS PROGRAM,

7886
04:58:17,950 --> 04:58:21,019
BECAUSE IT'S REALLY PART OF THIS

7887
04:58:21,019 --> 04:58:23,288
PRIORITY TO DIVERSIFY HIV

7888
04:58:23,288 --> 04:58:26,692
RESEARCH TO OTHER POPULATIONS.

7889
04:58:26,692 --> 04:58:31,797
>> GREAT, THANKS, HANEEFA.

7890
04:58:31,797 --> 04:58:33,465
LASTLY, WE'RE GOING TO HEAR FROM

7891
04:58:33,465 --> 04:58:35,634
THE AFRICAN COMMUNITY AND THAT'S

7892
04:58:35,634 --> 04:58:37,102
ELINA, IF YOU COULD INTRODUCE

7893
04:58:37,102 --> 04:58:37,369
YOURSELF.

7894
04:58:37,369 --> 04:58:38,537
>> THANK YOU VERY MUCH.

7895
04:58:38,537 --> 04:58:40,639
MY NAME IS ELINA MWASINGA.

7896
04:58:40,639 --> 04:58:42,140
I'M FROM MALAWI.

7897
04:58:42,140 --> 04:58:43,976
I LEAD AN ORGANIZATION CALLED

7898
04:58:43,976 --> 04:58:44,543
THE NATIONAL ASSOCIATION FOR

7899
04:58:44,543 --> 04:58:48,847
YOUNG PEOPLE LIVING WITH HIV.

7900
04:58:48,847 --> 04:58:52,884
HIV CURE RESEARCH ADVOCATE AND

7901
04:58:52,884 --> 04:58:55,254
I'M REALLY EXCITED TO BE HERE.

7902
04:58:55,254 --> 04:58:58,056
SO MY PERSONAL EXPERIENCE STEMS

7903
04:58:58,056 --> 04:59:01,360
FROM MY PERSONAL CHALLENGES THAT

7904
04:59:01,360 --> 04:59:04,229
I'VE FACED AS A PERSON LIVING

7905
04:59:04,229 --> 04:59:10,369
WITH HIV THE SO THE IMPACTS

7906
04:59:10,369 --> 04:59:13,905
FIRSTHAND LOOKING AT STIGMA

7907
04:59:13,905 --> 04:59:15,874
DISCRIMINATION, IT WAS REALLY

7908
04:59:15,874 --> 04:59:18,110
HARD, AND ALSO DEALING WITH THE

7909
04:59:18,110 --> 04:59:21,313
THE STRUGGLES OF THE PILL -- I

7910
04:59:21,313 --> 04:59:22,681
KNOW IT'S SOMETHING YOU JUST

7911
04:59:22,681 --> 04:59:24,049
HAVE TO ACCEPT BUT IT DOESN'T

7912
04:59:24,049 --> 04:59:24,783
GET ANY EASIER.

7913
04:59:24,783 --> 04:59:27,319
SO TO BE IN THIS SPACE TO LEARN

7914
04:59:27,319 --> 04:59:29,521
THAT THERE IS HOPE FOR HIV CURE

7915
04:59:29,521 --> 04:59:30,355
REALLY MEANS A LOT.

7916
04:59:30,355 --> 04:59:34,192
AND FOR THE YOUNG PEOPLE I

7917
04:59:34,192 --> 04:59:35,627
REPRESENT, SOMETIMES YOU MEET A

7918
04:59:35,627 --> 04:59:37,496
YOUNG PERSON ON THE VERGE OF

7919
04:59:37,496 --> 04:59:38,163
COMMITTING SUICIDE.

7920
04:59:38,163 --> 04:59:39,097
EVEN IF YOU TELL THEM THEY HAVE

7921
04:59:39,097 --> 04:59:40,132
TO TAKE THE DRUGS FOR THE REST

7922
04:59:40,132 --> 04:59:41,767
OF YOUR LIFE, IT DOESN'T BECOME

7923
04:59:41,767 --> 04:59:42,868
EASIER, BUT WHEN YOU TELL THEM

7924
04:59:42,868 --> 04:59:44,136
THAT, OH, THERE'S SOME

7925
04:59:44,136 --> 04:59:45,070
BREAKTHROUGHS, WE'VE GOT PEOPLE

7926
04:59:45,070 --> 04:59:48,040
BEING CURED OF HIV, THAT'S WHAT

7927
04:59:48,040 --> 04:59:48,473
GIVES THEM HOPE.

7928
04:59:48,473 --> 04:59:49,908
SO I REALLY APPRECIATE THE WORK

7929
04:59:49,908 --> 04:59:51,443
THAT THE RESEARCHERS ARE DOING

7930
04:59:51,443 --> 04:59:52,844
AND ALL THE KEY PLAYERS ARE

7931
04:59:52,844 --> 04:59:53,312
DOING.

7932
04:59:53,312 --> 04:59:54,680
I THINK YOU REALLY DESERVE A

7933
04:59:54,680 --> 04:59:56,315
ROUND OF APPLAUSE BECAUSE YOU

7934
04:59:56,315 --> 04:59:58,150
ARE DOING GREAT WORK.

7935
04:59:58,150 --> 04:59:59,584
AND BEING IN THIS SPACE IS SUCH

7936
04:59:59,584 --> 05:00:00,886
A GREAT OPPORTUNITY, SO I'M

7937
05:00:00,886 --> 05:00:02,454
REALLY, REALLY LOOKING FORWARD

7938
05:00:02,454 --> 05:00:04,790
TO THE MORE OUTCOMES OF THE WORK

7939
05:00:04,790 --> 05:00:08,560
THAT'S BEING DONE IN THE LAB, AS

7940
05:00:08,560 --> 05:00:10,962
WELL AS IN THE COMMUNITIES.

7941
05:00:10,962 --> 05:00:13,031
SO MY WORK IN HIV CURE RESEARCH

7942
05:00:13,031 --> 05:00:14,733
STARTED ABOUT A YEAR AGO, WHEN I

7943
05:00:14,733 --> 05:00:17,269
WAS ENGAGED WITH AVEC, AND I'VE

7944
05:00:17,269 --> 05:00:21,707
BEEN WORKING A LOT WITH JESSICA,

7945
05:00:21,707 --> 05:00:23,575
SANDRA, I'VE BEEN EXPOSED TO

7946
05:00:23,575 --> 05:00:24,776
THE -- AT FIRST IT'S REALLY

7947
05:00:24,776 --> 05:00:26,178
DIFFICULT TO EVEN UNDERSTAND

7948
05:00:26,178 --> 05:00:27,846
WHAT AN HIV RESERVOIR IS, BUT

7949
05:00:27,846 --> 05:00:28,947
I'M GLAD THAT I WAS VERY

7950
05:00:28,947 --> 05:00:30,382
FAMILIAR IN THIS ROOM WITH A LOT

7951
05:00:30,382 --> 05:00:33,085
OF WORDS AND I COULD RELATE TO A

7952
05:00:33,085 --> 05:00:37,889
LOT OF THE PRESENTATION.

7953
05:00:37,889 --> 05:00:41,026
SO I THINK LOOKING AT AFRICA IN

7954
05:00:41,026 --> 05:00:42,728
TERMS OF THE COMMUNITY, IN TERMS

7955
05:00:42,728 --> 05:00:46,531
OF HIV CURE, MY RESEARCH, AND

7956
05:00:46,531 --> 05:00:47,933
WE'RE ALSO DEALING WITH MYTH,

7957
05:00:47,933 --> 05:00:49,267
FOR EXAMPLE, THERE'S MYTH THAT

7958
05:00:49,267 --> 05:00:50,435
IF YOU SLEEP WITH A VIRGIN

7959
05:00:50,435 --> 05:00:52,070
YOU'RE GOING TO BE CURED.

7960
05:00:52,070 --> 05:00:53,939
SO I BELIEVE AS WE TALK ABOUT

7961
05:00:53,939 --> 05:00:55,607
HIV CURE RESEARCH, IT'S

7962
05:00:55,607 --> 05:00:59,978
IMPORTANT THAT WE START TO

7963
05:00:59,978 --> 05:01:00,645
EMPOWER COMMUNITIES WITH THIS

7964
05:01:00,645 --> 05:01:00,946
KNOWLEDGE.

7965
05:01:00,946 --> 05:01:03,348
I THINK WE LEARN A LOT FROM

7966
05:01:03,348 --> 05:01:03,682
COVID-19.

7967
05:01:03,682 --> 05:01:05,283
WHEN THE VACCINE CAME OUT, THERE

7968
05:01:05,283 --> 05:01:07,452
WAS SO MUCH UNRESPONSIVENESS

7969
05:01:07,452 --> 05:01:09,421
BECAUSE THERE WAS NOT THAT QUICK

7970
05:01:09,421 --> 05:01:10,622
KNOWLEDGE, BUT IF WE START NOW

7971
05:01:10,622 --> 05:01:13,558
AND WHEN THE CURE COMES, I THINK

7972
05:01:13,558 --> 05:01:15,327
WE WON'T SPEND MUCH TIME

7973
05:01:15,327 --> 05:01:17,863
CONVINCING PEOPLE WHO ALREADY

7974
05:01:17,863 --> 05:01:19,131
HAVE -- KNOWLEDGE, SO I THINK

7975
05:01:19,131 --> 05:01:20,766
THE TIME IS NOW TO START

7976
05:01:20,766 --> 05:01:22,501
BUILDING UP THIS IN OUR

7977
05:01:22,501 --> 05:01:25,604
COMMUNITIES AND WE NEED TO

7978
05:01:25,604 --> 05:01:27,873
ENSURE THAT -- CLAB RAYTIVE

7979
05:01:27,873 --> 05:01:29,608
EFFORTS AND PLATFORMS WHERE

7980
05:01:29,608 --> 05:01:30,475
RESEARCHERS CAN ALSO ENGAGE WITH

7981
05:01:30,475 --> 05:01:31,076
THE COMMUNITIES.

7982
05:01:31,076 --> 05:01:33,879
AND I THINK EARLIER WE TALKED

7983
05:01:33,879 --> 05:01:35,747
ABOUT THE INFRASTRUCTURES IN

7984
05:01:35,747 --> 05:01:37,816
AFRICA, SO ALREADY AFRICA

7985
05:01:37,816 --> 05:01:39,451
DEPENDS SO MUCH ON DONOR FUNDED

7986
05:01:39,451 --> 05:01:41,219
LOOKING AT PEPFAR AND GLOBAL

7987
05:01:41,219 --> 05:01:44,890
FUND LIKE ALMOST 80% GOES

7988
05:01:44,890 --> 05:01:46,892
TOWARDS COMMUNITIES AND OUR

7989
05:01:46,892 --> 05:01:49,628
GOVERNMENTS DO MAKE COMMITMENTS

7990
05:01:49,628 --> 05:01:50,729
TO CONTRIBUTE A CERTAIN

7991
05:01:50,729 --> 05:01:51,696
PERCENTAGE BUT THAT NEVER

7992
05:01:51,696 --> 05:01:57,402
HAPPENS, SO I THINK AS ALREADY

7993
05:01:57,402 --> 05:01:58,103
MENTIONED, IT'S IMPORTANT THAT

7994
05:01:58,103 --> 05:01:59,304
WE ALSO HOLD OUR GOVERNMENT

7995
05:01:59,304 --> 05:02:00,572
ACCOUNTABLE TO START PLANNING

7996
05:02:00,572 --> 05:02:02,808
FOR DOMESTIC RESOURCES TOWARDS

7997
05:02:02,808 --> 05:02:04,576
HIV CURE RESEARCH.

7998
05:02:04,576 --> 05:02:06,111
I'LL END HERE FOR NOW.

7999
05:02:06,111 --> 05:02:09,948
THANK YOU.

8000
05:02:09,948 --> 05:02:15,954
[APPLAUSE]

8001
05:02:15,954 --> 05:02:18,457
>> I WANT TO THANL THE
PANELISTS

8002
05:02:18,457 --> 05:02:19,524
FOR BEING BRIEF SO WE HAVE

8003
05:02:19,524 --> 05:02:20,592
PLENTY OF TIME BUT I'M GOING TO

8004
05:02:20,592 --> 05:02:21,426
DO A BRIEF SUMMARY.

8005
05:02:21,426 --> 05:02:24,896
I WANT TO STIMULATE SOME OF YOU

8006
05:02:24,896 --> 05:02:25,864
OUT IN THE AUDIENCE BEFORE YOU

8007
05:02:25,864 --> 05:02:28,600
LEAVE THIS CONFERENCE, AND ALSO

8008
05:02:28,600 --> 05:02:29,668
THE PANELISTS.

8009
05:02:29,668 --> 05:02:31,970
SO LET ME JUST SUMMARIZE WHAT

8010
05:02:31,970 --> 05:02:36,341
SOME OF THE THEMES THAT I HEARD.

8011
05:02:36,341 --> 05:02:39,377
FIRST IS THAT THERE IS A DIRE

8012
05:02:39,377 --> 05:02:40,846
NEED FOR MORE INTENSIVE TRAINING

8013
05:02:40,846 --> 05:02:42,881
IN THIS FIELD OF CURE RESEARCH.

8014
05:02:42,881 --> 05:02:46,051
IT'S HIGHLY TECHNICAL, AND THERE

8015
05:02:46,051 --> 05:02:48,887
NEEDS TO BE A LOT OF

8016
05:02:48,887 --> 05:02:51,923
COLLABORATION NORTH-SOUTH AND

8017
05:02:51,923 --> 05:02:52,457
SOUTH-SOUTH.

8018
05:02:52,457 --> 05:02:55,961
AND ACTUALLY, THE

8019
05:02:55,961 --> 05:02:57,929
COLLABORATORIES ARE THE PERFECT

8020
05:02:57,929 --> 05:03:00,232
EXAMPLE OF THAT TYPE OF

8021
05:03:00,232 --> 05:03:01,666
COLLABORATION.

8022
05:03:01,666 --> 05:03:03,001
I'VE SEEN IT INDIVIDUALLY WITH

8023
05:03:03,001 --> 05:03:04,069
THE DIFFERENT COLLABORATORIES

8024
05:03:04,069 --> 05:03:06,338
I'VE WORKED WITH OR HAVE BEEN

8025
05:03:06,338 --> 05:03:06,705
AFFILIATED WITH.

8026
05:03:06,705 --> 05:03:11,009
HOW YOU REACH OUT ACROSS

8027
05:03:11,009 --> 05:03:12,344
DIFFERENT INSTITUTIONS.

8028
05:03:12,344 --> 05:03:13,411
THAT COMPETITIVE SCIENTISTS GET

8029
05:03:13,411 --> 05:03:16,481
TOGETHER TO ACTUALLY WORK ON A

8030
05:03:16,481 --> 05:03:19,518
PARTICULAR PROBLEM AND FORGE

8031
05:03:19,518 --> 05:03:19,951
FORWARD.

8032
05:03:19,951 --> 05:03:24,456
SO I DO BELIEVE THAT THE CURE

8033
05:03:24,456 --> 05:03:28,393
COLLABORATORIES ARE PROBABLY THE

8034
05:03:28,393 --> 05:03:31,062
BEST SCENARIO IN WHICH WE CAN

8035
05:03:31,062 --> 05:03:33,732
EMBRACE THE PROBLEMS

8036
05:03:33,732 --> 05:03:37,002
INTERNATIONALLY ON CURE RESEARCH

8037
05:03:37,002 --> 05:03:38,336
AND HAVE THIS TYPE OF

8038
05:03:38,336 --> 05:03:38,970
COLLABORATION.

8039
05:03:38,970 --> 05:03:42,707
THE COLLABORATORIES NEED TO NOT

8040
05:03:42,707 --> 05:03:44,442
JUST BE IN ONE CITY AND MOST OF

8041
05:03:44,442 --> 05:03:46,978
THEM ARE NOT, THEY'RE MULTIPLE

8042
05:03:46,978 --> 05:03:48,647
CITIES IN THE U.S., BUT NOW THEY

8043
05:03:48,647 --> 05:03:54,152
NEED TO REACH OUT, HELP WITH THE

8044
05:03:54,152 --> 05:03:58,523
TRAINING OF OF REALLY EXCITING

8045
05:03:58,523 --> 05:03:59,491
SCIENTISTS, WELL EDUCATED BUT

8046
05:03:59,491 --> 05:04:01,960
NEED THE TRAINING IN SPECIFIC

8047
05:04:01,960 --> 05:04:04,229
TECHNIQUES AND HOW TO MOVE THAT

8048
05:04:04,229 --> 05:04:04,563
FORWARD.

8049
05:04:04,563 --> 05:04:07,799
I ALSO HEARD THAT WE NEEDED A

8050
05:04:07,799 --> 05:04:10,035
GREATER FOCUS OF THESE

8051
05:04:10,035 --> 05:04:11,736
COLLABORATORIES, THE ONES THAT

8052
05:04:11,736 --> 05:04:15,540
WE'VE ALL HEARD FROM, ON NON-B

8053
05:04:15,540 --> 05:04:17,976
SUBTYPES.

8054
05:04:17,976 --> 05:04:19,511
THEY MAKE UP A SMALL PROPORTION

8055
05:04:19,511 --> 05:04:20,178
OF THE GLOBAL PROBLEM THAT WE

8056
05:04:20,178 --> 05:04:22,914
FACE.

8057
05:04:22,914 --> 05:04:24,115
AND SO THAT'S A CHALLENGE TO ALL

8058
05:04:24,115 --> 05:04:27,185
OF YOU.

8059
05:04:27,185 --> 05:04:28,353
START THINKING OUT OF THE BOX.

8060
05:04:28,353 --> 05:04:30,989
GET SOME CLADE Cs, SOME Ds,

8061
05:04:30,989 --> 05:04:32,924
SOME As, SOME RECOMBINANTS.

8062
05:04:32,924 --> 05:04:35,126
CAN YOU DO IPDA EASILY, SO THAT

8063
05:04:35,126 --> 05:04:39,264
YOU CAN MEASURE THE RESERVOIRS

8064
05:04:39,264 --> 05:04:40,599
EFFECTIVELY WHEN YOU'RE DEALING

8065
05:04:40,599 --> 05:04:44,569
WITH NON-CLADE Bs.

8066
05:04:44,569 --> 05:04:45,837
SO THAT WAS ONE OF THE THINGS

8067
05:04:45,837 --> 05:04:46,404
BROUGHT UP.

8068
05:04:46,404 --> 05:04:47,973
I ALSO HEARD THAT CLINICAL

8069
05:04:47,973 --> 05:04:51,910
RESEARCH IS VERY POSSIBLE, THAT

8070
05:04:51,910 --> 05:04:55,146
THE COMMUNITY EMBRACES THAT,

8071
05:04:55,146 --> 05:04:57,582
THAT THOSE WHO WORK IN AFRICA,

8072
05:04:57,582 --> 05:05:00,085
WHETHER IT'S GETTING INTESTINAL

8073
05:05:00,085 --> 05:05:04,055
BIOPSIES OR IT'S DOING TREATMENT

8074
05:05:04,055 --> 05:05:07,425
INTERRUPTIONS, OTHER TYPES OF

8075
05:05:07,425 --> 05:05:07,826
INVESTIGATIONS.

8076
05:05:07,826 --> 05:05:12,097
ALL OF THAT IS SOMETHING THAT

8077
05:05:12,097 --> 05:05:13,565
CAN BE DONE IN AFRICA, DOESN'T

8078
05:05:13,565 --> 05:05:18,570
HAVE TO JUST BE DONE IN THE U.S.

8079
05:05:18,570 --> 05:05:19,537
AND I THINK THE COMMUNITY WANTS

8080
05:05:19,537 --> 05:05:21,539
TO BE INVOLVED IN THAT, THAT THE

8081
05:05:21,539 --> 05:05:24,676
SCIENTIFIC LEADERS CAN REALLY

8082
05:05:24,676 --> 05:05:27,946
TAKE ON SOME OF THESE

8083
05:05:27,946 --> 05:05:28,847
INITIATIVES, SO EVEN THOUGH

8084
05:05:28,847 --> 05:05:30,615
WE'RE TALKING ABOUT CRISPR AND

8085
05:05:30,615 --> 05:05:35,153
WHAT WE'RE DOING WITH CRISPR IN

8086
05:05:35,153 --> 05:05:36,554
U.S. SCIENCE LABORATORIES, I

8087
05:05:36,554 --> 05:05:38,123
THINK SOME OF THAT CAN BE DONE

8088
05:05:38,123 --> 05:05:40,091
WITH THE NON-CLADE Bs AND IT

8089
05:05:40,091 --> 05:05:43,862
CAN BE DONE IN AFRICA I AND THE

8090
05:05:43,862 --> 05:05:45,096
COHORTS CAN BE BUILT IN THE

8091
05:05:45,096 --> 05:05:47,932
MEANTIME TO EFFICIENTLY GO

8092
05:05:47,932 --> 05:05:49,834
FORWARD FOR THOSE TYPES OF

8093
05:05:49,834 --> 05:05:51,269
INVESTIGATIONS.

8094
05:05:51,269 --> 05:05:54,506
I HEARD A NEED FOR

8095
05:05:54,506 --> 05:05:55,707
INFRASTRUCTURE.

8096
05:05:55,707 --> 05:05:58,777
THAT THE TYPE OF EQUIPMENT YOU

8097
05:05:58,777 --> 05:06:02,480
ALL USE IS NOT IN AFRICA.

8098
05:06:02,480 --> 05:06:04,349
IN VERY FEW PLACES.

8099
05:06:04,349 --> 05:06:07,786
MAYBE SOUTH AFRICA'S GOT SOME IN

8100
05:06:07,786 --> 05:06:09,087
CAPETOWN, MAYBE IN JOHANNESBURG,

8101
05:06:09,087 --> 05:06:10,655
BUT CERTAINLY NOT IN THE EASTERN

8102
05:06:10,655 --> 05:06:13,725
CAPE WHERE I'VE WORKED.

8103
05:06:13,725 --> 05:06:15,026
IT CERTAINLY JUST STARTING TO

8104
05:06:15,026 --> 05:06:18,496
COME INTO UGANDA.

8105
05:06:18,496 --> 05:06:21,900
THE FIRST DIGITAL DOP L DROPLETR

8106
05:06:21,900 --> 05:06:23,868
JUST MAKING ITS WAY INTO UGANDA.

8107
05:06:23,868 --> 05:06:25,937
SO THERE'S A REAL NEED TO

8108
05:06:25,937 --> 05:06:27,338
LOOKING AT THAT TECHNOLOGY.

8109
05:06:27,338 --> 05:06:30,308
YOU CAN TRAIN SOMEONE IN YOUR

8110
05:06:30,308 --> 05:06:32,277
LAB, PUT THEM BACK IN AFRICA AT

8111
05:06:32,277 --> 05:06:34,579
THEIR HOME WITH THEIR COMMUNITY,

8112
05:06:34,579 --> 05:06:36,314
AND THEY MAY OR MAY NOT BE ABLE

8113
05:06:36,314 --> 05:06:38,483
TO FOLLOW THROUGH ON SOME OF

8114
05:06:38,483 --> 05:06:40,251
THESE UNLESS THERE'S AN INVEST M

8115
05:06:40,251 --> 05:06:43,054
IN INFRASTRUCTURE.

8116
05:06:43,054 --> 05:06:44,489
AND EDWARD SAID THE AFRICAN

8117
05:06:44,489 --> 05:06:47,025
GOVERNMENTS AND THEIR FUNDING

8118
05:06:47,025 --> 05:06:49,394
AGENCIES NEED TO PULL A LITTLE

8119
05:06:49,394 --> 05:06:51,896
BIT OF WEIGHT IN THAT PROCESS.

8120
05:06:51,896 --> 05:06:53,131
WHETHER THAT'S THESIBLE OR NOT,

8121
05:06:53,131 --> 05:06:57,235
THESE FEASIBLE ORNOT, I'M GOINGO

8122
05:06:57,235 --> 05:06:58,436
EDWARD AND THE COMMUNITIES TO

8123
05:06:58,436 --> 05:06:59,070
RAISE THAT.

8124
05:06:59,070 --> 05:07:01,840
WE HEARD THAT THERE IS A FUNDING

8125
05:07:01,840 --> 05:07:03,174
OPPORTUNITY.

8126
05:07:03,174 --> 05:07:07,112
DEADLINES, NOVEMBER 10TH.

8127
05:07:07,112 --> 05:07:08,980
CALLED AFRCURE.

8128
05:07:08,980 --> 05:07:09,848
YOU SAWED ADD.

8129
05:07:09,848 --> 05:07:12,083
READ THROUGH IT.

8130
05:07:12,083 --> 05:07:13,418
IT'S A MENTORSHIP RELATIONSHIP

8131
05:07:13,418 --> 05:07:16,321
BUT IT'S WHAT STARTS THE PROC 

8132
05:07:16,321 --> 05:07:17,388
PROCESS.

8133
05:07:17,388 --> 05:07:18,923
AND CAN BRING A LOT OF RICHES TO

8134
05:07:18,923 --> 05:07:21,693
THE HOST LABORATORIES THAT ARE

8135
05:07:21,693 --> 05:07:24,763
MENTORING TO THE ONES TAKING

8136
05:07:24,763 --> 05:07:26,364
PLACE IN VARIOUS COUNTRIES OF

8137
05:07:26,364 --> 05:07:30,034
AFRICA.

8138
05:07:30,034 --> 05:07:30,935
AND WE HEARD FROM THE COMMUNITY

8139
05:07:30,935 --> 05:07:32,604
THERE'S A REAL NEED FOR THIS

8140
05:07:32,604 --> 05:07:33,605
TYPE OF RESEARCH TO MOVE

8141
05:07:33,605 --> 05:07:35,673
FORWARD.

8142
05:07:35,673 --> 05:07:39,644
I WOULD SAY 20 YEARS AGO, NO ONE

8143
05:07:39,644 --> 05:07:41,613
OR VERY FEW PEOPLE FELT THAT WE

8144
05:07:41,613 --> 05:07:44,983
WERE GOING TO BE ABLE TO BRING

8145
05:07:44,983 --> 05:07:48,119
OUR BRAND NEW TRIPLE THERAPY

8146
05:07:48,119 --> 05:07:52,490
ANTIRETROVIRAL DRUGS TO AFRICA.

8147
05:07:52,490 --> 05:07:53,858
AND LO AND BEHOLD, YES, IT'S 20

8148
05:07:53,858 --> 05:07:57,028
YEARS LATER, BUT WE HAVE, IN THE

8149
05:07:57,028 --> 05:08:00,198
RANGE OF ABOUT 30 MILLION PEOPLE

8150
05:08:00,198 --> 05:08:01,933
ON TREATMENT, THE VAST MAJORITY

8151
05:08:01,933 --> 05:08:05,603
OF THAT NUMBER IS IN AFRICA, AND

8152
05:08:05,603 --> 05:08:08,807
THE VIRAL SUPPRESSION RATES IN

8153
05:08:08,807 --> 05:08:11,843
SOME PLACES LIKE RAKAI OR IN

8154
05:08:11,843 --> 05:08:13,745
MALAWI AND SOME OTHER PLACES IS

8155
05:08:13,745 --> 05:08:15,079
ACTUALLY BETTER THAN IT IS IN

8156
05:08:15,079 --> 05:08:16,614
THE SOUTH OF THE U.S.

8157
05:08:16,614 --> 05:08:18,950
IT'S A HUGE SUCCESS, AND IT

8158
05:08:18,950 --> 05:08:22,654
WOULD BE ASHAMED TO BE WAITING

8159
05:08:22,654 --> 05:08:24,656
FOR SO LONG TO START ENGAGING

8160
05:08:24,656 --> 05:08:27,659
THE CURE RESEARCH ON THE

8161
05:08:27,659 --> 05:08:29,227
CONTINENT.

8162
05:08:29,227 --> 05:08:31,863
SO LET ME STOP A BIT ON

8163
05:08:31,863 --> 05:08:33,565
SUMMARIZING SOME OF THE POINTS

8164
05:08:33,565 --> 05:08:36,534
THAT I JUST HEARD.

8165
05:08:36,534 --> 05:08:37,735
THERE WERE OTHER POINTS MADE,

8166
05:08:37,735 --> 05:08:38,970
BUT I'M GOING TO THROW A

8167
05:08:38,970 --> 05:08:41,873
CHALLENGE OUT TO THE AUDIENCE.

8168
05:08:41,873 --> 05:08:44,442
WHY DO RESEARCH IN AFRICA?

8169
05:08:44,442 --> 05:08:45,643
WHAT'S THE MOTIVATION?

8170
05:08:45,643 --> 05:08:47,979
WHAT'S THE RESEARCH QUESTIONS?

8171
05:08:47,979 --> 05:08:49,848
AND I THINK EACH ONE OF YOU WILL

8172
05:08:49,848 --> 05:08:56,354
HAVE TO THINK ABOUT THAT, BUT

8173
05:08:56,354 --> 05:08:57,755
LET ME SUMMARIZE SOME THAT CARL

8174
05:08:57,755 --> 05:08:58,756
AND HIS COLLEAGUES HAVE COME UP

8175
05:08:58,756 --> 05:08:59,624
WITH AND IF THEY'RE THINKING

8176
05:08:59,624 --> 05:09:01,192
ABOUT IT, YOU DEFINITELY SHOULD

8177
05:09:01,192 --> 05:09:03,094
BE THINKING ABOUT IT FOR FUTURE

8178
05:09:03,094 --> 05:09:03,962
FUNDING.

8179
05:09:03,962 --> 05:09:07,031
SO WHAT ARE SOME OF THE KEY

8180
05:09:07,031 --> 05:09:08,333
UNKNOWNS OUT THERE?

8181
05:09:08,333 --> 05:09:10,535
WHAT DIFFERENCES EXIST AMONG THE

8182
05:09:10,535 --> 05:09:12,303
DIFFERENT HIV SUBTYPES, AND THE

8183
05:09:12,303 --> 05:09:16,708
DIFFERENT POPULATIONS?

8184
05:09:16,708 --> 05:09:18,977
WITH RESPECT TO THE RESERVOIR

8185
05:09:18,977 --> 05:09:21,613
COMPOSITION, ITS CLONALITY, IT'S

8186
05:09:21,613 --> 05:09:24,249
DECAY, ARE DYNAMICS DIFFERENT

8187
05:09:24,249 --> 05:09:26,217
WITH THESE OTHER SUBTYPES?

8188
05:09:26,217 --> 05:09:28,920
WHAT ARE THE RATES OF POST

8189
05:09:28,920 --> 05:09:31,222
TREATMENT CONTROL?

8190
05:09:31,222 --> 05:09:33,825
WHAT'S THE EFFECTIVENESS OF

8191
05:09:33,825 --> 05:09:37,428
CURATIVE STRATEGIES AS YOU START

8192
05:09:37,428 --> 05:09:42,267
TESTING THESE IN THE U.S.?

8193
05:09:42,267 --> 05:09:45,203
WHAT ROLE DOES SEX, AGE,

8194
05:09:45,203 --> 05:09:47,505
COMORBIDITIES, COMORTALITIES,

8195
05:09:47,505 --> 05:09:49,407
COINFECTION, GENETICS,

8196
05:09:49,407 --> 05:09:51,376
ENVIRONMENTAL FACTORS, AND

8197
05:09:51,376 --> 05:09:55,747
GEOGRAPHY AT LARGE, PLAY IN

8198
05:09:55,747 --> 05:09:57,015
THOSE DIFFERENCES?  SO LOTS OF

8199
05:09:57,015 --> 05:09:59,083
THINGS TO THINK ABOUT.

8200
05:09:59,083 --> 05:10:00,151
THAT'S JUST SORT OF THE TIP OF

8201
05:10:00,151 --> 05:10:01,419
THE ICEBERG WITHOUT GETTING TOO

8202
05:10:01,419 --> 05:10:02,520
TECHNICAL, BUT ONE COULD EASILY

8203
05:10:02,520 --> 05:10:05,590
GO INTO THE TECHNICALITIES OF

8204
05:10:05,590 --> 05:10:11,229
THOSE TYPES OF ISSUES.

8205
05:10:11,229 --> 05:10:12,864
SO I WILL DEFINITELY STOP THERE,

8206
05:10:12,864 --> 05:10:14,999
THAT'S MY FIVE-MINUTE SPIEL.

8207
05:10:14,999 --> 05:10:19,137
I SEE JESSICA AT THE MICROPHONE,

8208
05:10:19,137 --> 05:10:20,038
AND ALSO OVER THERE, I CAN'T SEE

8209
05:10:20,038 --> 05:10:24,242
AS WELL, BUT LET ME OPEN UP THE

8210
05:10:24,242 --> 05:10:25,076
MICS BECAUSE I WANT YOU TO

8211
05:10:25,076 --> 05:10:29,447
ENGAGE WITH THE PANELISTS AND

8212
05:10:29,447 --> 05:10:32,083
HEAR FROM YOU AS TO WHAT YOU

8213
05:10:32,083 --> 05:10:34,352
THINK IS FEASIBLE, HEAR FROM THE

8214
05:10:34,352 --> 05:10:36,955
PANELISTS WHAT THEY FEEL WOULD

8215
05:10:36,955 --> 05:10:46,331
BE THE BEST WAY FORWARD FOR THEM

8216
05:10:46,331 --> 05:10:47,765
AND THEIR COLLEAGUES WORKING IN

8217
05:10:47,765 --> 05:10:48,032
AFRICA.

8218
05:10:48,032 --> 05:10:48,399
>> I'LL START.

8219
05:10:48,399 --> 05:10:52,704
SO I HAVE A QUESTION FOR THE

8220
05:10:52,704 --> 05:10:53,037
PANEL.

8221
05:10:53,037 --> 05:10:54,339
I'M INTERESTED TO HEAR HOW MUCH

8222
05:10:54,339 --> 05:10:56,674
YOU FEEL IT IS A BARRIER TO

8223
05:10:56,674 --> 05:11:01,579
RESEARCH ON THE CONTINENT,

8224
05:11:01,579 --> 05:11:02,814
AVAILABILITY OF FUNDING THAT CAN

8225
05:11:02,814 --> 05:11:05,984
BE HELD BY AFRICAN PIs.

8226
05:11:05,984 --> 05:11:08,152
SO THIS QUESTION STEMS FROM MY

8227
05:11:08,152 --> 05:11:09,954
OBSERVATION THAT NOT ONLY IS IT

8228
05:11:09,954 --> 05:11:14,258
THAT FREQUENTLY THE SAMPLES ARE

8229
05:11:14,258 --> 05:11:18,196
COLLECTED IN E UGANDA WHERE I WK

8230
05:11:18,196 --> 05:11:19,630
AND SHIPPED BACK TO NORTH

8231
05:11:19,630 --> 05:11:19,864
AMERICA.

8232
05:11:19,864 --> 05:11:21,733
I'M IN CANADA, ALSO MY

8233
05:11:21,733 --> 05:11:22,567
COLLABORATORS IN THE UNITED

8234
05:11:22,567 --> 05:11:23,701
STATES, BUT ALSO THE MONEY AND

8235
05:11:23,701 --> 05:11:25,770
THEN THE PAPERS TEND TO GO THAT

8236
05:11:25,770 --> 05:11:26,971
WAY.

8237
05:11:26,971 --> 05:11:29,140
SO AS A CANADIAN, OUR LARGE

8238
05:11:29,140 --> 05:11:30,775
FUNDING ORGANIZATION IS CIHR FOR

8239
05:11:30,775 --> 05:11:34,345
HEALTH RESEARCH, AND YOU HAVE TO

8240
05:11:34,345 --> 05:11:36,347
BE AT A CANADIAN INSTITUTE TO

8241
05:11:36,347 --> 05:11:37,548
APPLY FOR THAT FUNDING.

8242
05:11:37,548 --> 05:11:39,083
AND I KNOW THE NIH IS MORE OPEN

8243
05:11:39,083 --> 05:11:40,752
AND YOU CAN APPLY

8244
05:11:40,752 --> 05:11:41,953
INTERNATIONALLY TO NIH GRANTS,

8245
05:11:41,953 --> 05:11:43,154
BUT IT'S HARD TO COMPETE FOR

8246
05:11:43,154 --> 05:11:44,589
THEM.

8247
05:11:44,589 --> 05:11:49,961
AND SO WITH THE LACK OF

8248
05:11:49,961 --> 05:11:51,262
AVAILABILITY OF LOCAL NATIONAL

8249
05:11:51,262 --> 05:11:52,230
FUNDING, I'LL SPEAK SPECIFICALLY

8250
05:11:52,230 --> 05:11:54,332
FOR UGANDA LOCALLY, IT HARD FOR

8251
05:11:54,332 --> 05:11:55,733
MY UGANDAN COLLEAGUES TO COMPETE

8252
05:11:55,733 --> 05:11:58,236
FOR NIH FUNDING AND THEY SIMPLY

8253
05:11:58,236 --> 05:11:59,570
CAN'T, FOR CHR FUNDING.

8254
05:11:59,570 --> 05:12:02,206
SO THEN WE HAVE THIS SITUATION

8255
05:12:02,206 --> 05:12:03,641
WHERE THE CANADIAN IS APPLYING

8256
05:12:03,641 --> 05:12:05,043
FOR THE GRANT, HOLDING THE

8257
05:12:05,043 --> 05:12:07,178
GRANT, AND THEN TRANSFERS A

8258
05:12:07,178 --> 05:12:07,445
SUBAWARD.

8259
05:12:07,445 --> 05:12:08,579
THE SAMPLES ARE COLLECTED THERE,

8260
05:12:08,579 --> 05:12:09,981
AND THEN THE SAMPLES COME BACK

8261
05:12:09,981 --> 05:12:13,017
AND ISN'T IT SO FRUSTRATING WHEN

8262
05:12:13,017 --> 05:12:14,252
THE LAST PERSON WHO TOUCHES THE

8263
05:12:14,252 --> 05:12:15,686
SAMPLE IS THE LAST AUTHOR OR THE

8264
05:12:15,686 --> 05:12:17,655
FIRST AUTHOR ON THE PAPER.

8265
05:12:17,655 --> 05:12:24,595
AND THAT PA PARADYNAMIC, I WONDD

8266
05:12:24,595 --> 05:12:26,798
HOW WE CAN SHIFT THAT.

8267
05:12:26,798 --> 05:12:31,202
I THINK THE AFRICARE -- WE CAN

8268
05:12:31,202 --> 05:12:32,637
HAVE MORE PEOPLE TRAINED,

8269
05:12:32,637 --> 05:12:34,772
COMPETE FOR NIH GRANTS FOR

8270
05:12:34,772 --> 05:12:35,106
HPIs.

8271
05:12:35,106 --> 05:12:37,075
THESE ARE MY OWN THOUGHTS BUT

8272
05:12:37,075 --> 05:12:38,476
I'M INTERESTED HOW THE PANEL

8273
05:12:38,476 --> 05:12:39,710
VIEWS THAT, DO YOU VIEW THAT AS

8274
05:12:39,710 --> 05:12:41,879
BEING A MAJOR BARRIER AND WHAT

8275
05:12:41,879 --> 05:12:43,214
MIGHT WE BE ABLE TO DO TO

8276
05:12:43,214 --> 05:12:48,052
ADDRESS THAT?

8277
05:12:48,052 --> 05:12:51,823
>> I CAN TAKE A STAB AT
THAT.

8278
05:12:51,823 --> 05:12:54,025
SO LET ME START FROM A POSITIVE

8279
05:12:54,025 --> 05:12:59,997
ASPECT OF THIS.

8280
05:12:59,997 --> 05:13:01,566
I THINK AFRICA HAS SO MUCH

8281
05:13:01,566 --> 05:13:03,634
POTENTIAL AND CAN COMPETE AND BE

8282
05:13:03,634 --> 05:13:08,005
AN EQUAL PARTNER ON THE TABLE TO

8283
05:13:08,005 --> 05:13:12,076
SHIFT THE HIV AGENDA.

8284
05:13:12,076 --> 05:13:13,811
WE DEMONSTRATED DURING COVID, WE

8285
05:13:13,811 --> 05:13:16,848
LED THE WORLD IN CHARACTERIZING

8286
05:13:16,848 --> 05:13:19,150
SARS-COV-2 2, THE VARIANTS AND

8287
05:13:19,150 --> 05:13:19,851
CONTRIBUTED SIGNIFICANT RI TO

8288
05:13:19,851 --> 05:13:22,253
THE DEVELOPMENT OF PROTECTIVE

8289
05:13:22,253 --> 05:13:23,321
VACCINES THAT HELPED THE WORLD.

8290
05:13:23,321 --> 05:13:30,428
SO THAT'S A CLEAR DEMONSTRATION.

8291
05:13:30,428 --> 05:13:33,397
IN PLACES WHERE YOU HAVE

8292
05:13:33,397 --> 05:13:34,365
LEADERSHIP, THEY UNDERSTAND THE

8293
05:13:34,365 --> 05:13:35,466
PROBLEMS, THEY CAN REACH OUT TO

8294
05:13:35,466 --> 05:13:38,102
THE STAKEHOLDERS, TO EVEN

8295
05:13:38,102 --> 05:13:39,070
MOBILIZE LOCAL RESOURCES.

8296
05:13:39,070 --> 05:13:40,705
I CAN GIVE AN EXAMPLE OF

8297
05:13:40,705 --> 05:13:42,373
TANZANIA, THE GOVERNMENT OF

8298
05:13:42,373 --> 05:13:44,208
TANZANIA HAS PUT UP 20 MILLION

8299
05:13:44,208 --> 05:13:50,681
U.S. DOLLARS IN RESEARCH FOR

8300
05:13:50,681 --> 05:13:53,084
SICKLE CELL ANEMIA, GENE THERAPY

8301
05:13:53,084 --> 05:13:54,085
RESEARCH IN SICKLE CELL ANEMIA.

8302
05:13:54,085 --> 05:13:54,919
SO THERE IS THAT.

8303
05:13:54,919 --> 05:13:56,120
SO WHAT WE ARE LACKING IN TERMS

8304
05:13:56,120 --> 05:13:59,757
OF THE HIV CURE PROGRAM IS

8305
05:13:59,757 --> 05:14:00,725
LEADERSHIP, AND OWNERSHIP.

8306
05:14:00,725 --> 05:14:04,162
AND GETTING BACK TO YOUR

8307
05:14:04,162 --> 05:14:05,363
QUESTION, WHEN THE GRANT IS

8308
05:14:05,363 --> 05:14:10,568
WRITTEN BY A CANADIAN WITH -- IN

8309
05:14:10,568 --> 05:14:13,204
AFRICA, WHOSE IDEA IS THAT?

8310
05:14:13,204 --> 05:14:16,140
WHO CONCEPTUALIZED THE IDEA?

8311
05:14:16,140 --> 05:14:18,776
IS IT THE CANADIAN INVESTIGATOR

8312
05:14:18,776 --> 05:14:19,810
OR AFRICAN INVESTIGATOR?

8313
05:14:19,810 --> 05:14:22,280
WHEN THE FUNDING KOMEN COMES TH,

8314
05:14:22,280 --> 05:14:23,614
WHERE DO THE BULK OF THE MONEY

8315
05:14:23,614 --> 05:14:24,549
GO, THE OVERHEADS AND

8316
05:14:24,549 --> 05:14:24,982
EVERYTHING?

8317
05:14:24,982 --> 05:14:26,684
AND WHAT IS CONTAINED IN THE

8318
05:14:26,684 --> 05:14:27,685
SUBAWARD?

8319
05:14:27,685 --> 05:14:31,489
SO IF YOU GET A MILLION DOLLARS

8320
05:14:31,489 --> 05:14:35,893
AND YOU SUBAWARD 100,000, TO

8321
05:14:35,893 --> 05:14:38,663
ACTUALLY DO ANY MEANINGFUL BASIC

8322
05:14:38,663 --> 05:14:39,730
SCIENCE RESEARCH, IN THE GIPPING

8323
05:14:39,730 --> 05:14:40,231
I SAID THAT.

8324
05:14:40,231 --> 05:14:41,399
THE COST OF DOING RESEARCH ON

8325
05:14:41,399 --> 05:14:42,567
THE CONTINENT IS MUCH, MUCH

8326
05:14:42,567 --> 05:14:42,934
HIGHER.

8327
05:14:42,934 --> 05:14:44,969
SO THE BIGGEST BARRIER IS

8328
05:14:44,969 --> 05:14:49,674
RESOURCES TO BEGIN WITH.

8329
05:14:49,674 --> 05:14:53,578
BECAUSE THERE'S FEWER RESOURCES,

8330
05:14:53,578 --> 05:14:55,046
WE HAVE TO DEPEND ON THE WEST.

8331
05:14:55,046 --> 05:14:56,781
THE SOLUTION TO THAT IS DIRECT

8332
05:14:56,781 --> 05:15:00,384
FUNDING, OPPORTUNITIES TO FUND

8333
05:15:00,384 --> 05:15:02,420
AFRICA DIRECTLY BEING INVOLVED

8334
05:15:02,420 --> 05:15:03,854
IN THE CONCEPTUALIZATION OF THE

8335
05:15:03,854 --> 05:15:07,825
IDEA SO THAT THE IDEA TAKES INTO

8336
05:15:07,825 --> 05:15:09,060
ACCOUNT THE REALITY ON THE

8337
05:15:09,060 --> 05:15:15,700
GROUND.

8338
05:15:15,700 --> 05:15:17,134
>> I'M GOING TO KEEP THIS
MOVING

8339
05:15:17,134 --> 05:15:18,336
BECAUSE THE LINE IS BUILDING AND

8340
05:15:18,336 --> 05:15:20,171
THAT WAS AN EXCELLENT RESPONSE.

8341
05:15:20,171 --> 05:15:22,473
NEXT QUESTION.

8342
05:15:22,473 --> 05:15:23,708
>> THANKS.

8343
05:15:23,708 --> 05:15:25,977
I'M MOHETH FROM WEILL CORNELL.

8344
05:15:25,977 --> 05:15:30,014
I WORK IN DR. GUIN LEE'S LAB,

8345
05:15:30,014 --> 05:15:33,651
AND I HAD A COUPLE COMMENTS.

8346
05:15:33,651 --> 05:15:36,120
FIRST I AGREE WITH ZAZA THAT

8347
05:15:36,120 --> 05:15:37,822
RESEARCH IN AFRICA OR LIKE

8348
05:15:37,822 --> 05:15:40,224
OUTSIDE OF THE AMERICAN

8349
05:15:40,224 --> 05:15:41,492
CONTINENT AND EUROPE, IT COSTS A

8350
05:15:41,492 --> 05:15:42,893
LOT.

8351
05:15:42,893 --> 05:15:45,196
I WAS ABOUT TO ASK YOU IF YOU

8352
05:15:45,196 --> 05:15:52,470
HAD ANY PLANS TO -- I MEAN,

8353
05:15:52,470 --> 05:15:55,906
ANCHORAGE MANUFACTURING AND ALSO

8354
05:15:55,906 --> 05:15:57,842
QUALITY ANALYSIS AND CERTIFYING

8355
05:15:57,842 --> 05:16:00,011
YOUR OWN REAGENTS SO THAT THE

8356
05:16:00,011 --> 05:16:02,079
COSTS COULD GO DOWN AS MUCH AS

8357
05:16:02,079 --> 05:16:04,215
YOU CAN POSSIBLY BRING IT DOWN.

8358
05:16:04,215 --> 05:16:06,417
AND WOULD THAT ACTUALLY HELP YOU

8359
05:16:06,417 --> 05:16:10,288
IN ANY WAY TO CONDUCT MORE

8360
05:16:10,288 --> 05:16:11,222
MEANINGFUL RESEARCH?

8361
05:16:11,222 --> 05:16:12,490
I UNDERSTAND THAT TRAINING IS

8362
05:16:12,490 --> 05:16:13,791
IMPORTANT, BUT WITHOUT

8363
05:16:13,791 --> 05:16:14,792
RESOURCES, YOU'RE NOT GOING TO

8364
05:16:14,792 --> 05:16:16,327
BE ABLE TO DO A LOT OF

8365
05:16:16,327 --> 05:16:19,263
MEANINGFUL RESEARCH FOR YOU TO

8366
05:16:19,263 --> 05:16:24,001
EVEN REACH FOR THE INCENTIVES

8367
05:16:24,001 --> 05:16:30,074
LIKE WAS MENTIONED.

8368
05:16:30,074 --> 05:16:32,743
IF YOU'RE NOT ACTUALLY ABLE TO

8369
05:16:32,743 --> 05:16:34,312
DO MEANINGFUL RESEARCH HOW ARE

8370
05:16:34,312 --> 05:16:35,446
YOU EVEN GOING TO APPLY FOR

8371
05:16:35,446 --> 05:16:36,981
THESE AWARDS AND FELLOWSHIPS

8372
05:16:36,981 --> 05:16:39,850
WITHOUT RESOURCES?

8373
05:16:39,850 --> 05:16:41,919
SO MY QUESTION IS HOW ARE YOU

8374
05:16:41,919 --> 05:16:43,521
PLANNING ON ADDRESSING THE

8375
05:16:43,521 --> 05:16:44,188
MANUFACTURING AND THE

8376
05:16:44,188 --> 05:16:47,058
ACCESSIBILITY TO REAGENTS?

8377
05:16:47,058 --> 05:16:50,227
>> SO THAT IS A MUCH
BIGGER

8378
05:16:50,227 --> 05:16:51,529
PROBLEM THAT ONE INVESTIGATOR

8379
05:16:51,529 --> 05:16:54,965
CANNOT SOLVE.

8380
05:16:54,965 --> 05:16:56,701
SO IT'S A BUSINESS PROBLEM.

8381
05:16:56,701 --> 05:16:58,436
WE CANNOT ORDER REAGENTS

8382
05:16:58,436 --> 05:16:59,737
DIRECTLY FROM THE MANUFACTURERS

8383
05:16:59,737 --> 05:17:01,305
IN THE U.S.

8384
05:17:01,305 --> 05:17:02,373
THERE'S A MIDDLEMAN.

8385
05:17:02,373 --> 05:17:05,976
AND THE MIDDLEMAN PUTS UP A BIG

8386
05:17:05,976 --> 05:17:07,078
MARKUP FOR US TO GET THE REAGENT

8387
05:17:07,078 --> 05:17:08,512
TO YOUR LAB, YOU HAVE TO GO

8388
05:17:08,512 --> 05:17:11,782
THROUGH A LOCAL SUPPLIER, AND

8389
05:17:11,782 --> 05:17:12,917
YOU DEPEND ON THEM.

8390
05:17:12,917 --> 05:17:14,552
FOR THEM THEY WANT TO MAKE A

8391
05:17:14,552 --> 05:17:17,221
PROFIT SO THEY CANNOT SHIP AN

8392
05:17:17,221 --> 05:17:18,489
ANTIBODY FOR YOU BECAUSE THEY

8393
05:17:18,489 --> 05:17:21,892
WON'T MA MAKE A PROFIT SO YOU'LL

8394
05:17:21,892 --> 05:17:24,195
HAVE TO WAIT FOR THEM TO MAKE

8395
05:17:24,195 --> 05:17:25,629
VOLUMES, SOMETIMES THEY ARE WAY

8396
05:17:25,629 --> 05:17:26,931
EXAGGERATED AND I THINK THAT

8397
05:17:26,931 --> 05:17:28,699
BUSINESS IS UNREGULATED.

8398
05:17:28,699 --> 05:17:30,935
THE SOLUTION TO THAT IS THAT THE

8399
05:17:30,935 --> 05:17:31,669
FUNDERS NEED TO COME TOGETHER,

8400
05:17:31,669 --> 05:17:35,072
THE NIH, THE WELLCOME TRUST, THE

8401
05:17:35,072 --> 05:17:36,741
BILL GATES FOUNDATION TO

8402
05:17:36,741 --> 05:17:38,309
NEGOTIATE ON OUR BEHALF TO THESE

8403
05:17:38,309 --> 05:17:39,777
COMPANIES TO FIND A WAY IN WHICH

8404
05:17:39,777 --> 05:17:41,011
WE CAN LOWER THE COST, AND IT

8405
05:17:41,011 --> 05:17:43,314
HAS TO BE A CONDITION LIKE IF

8406
05:17:43,314 --> 05:17:52,289
YOU'RE GOING TO BUY A FLOW SIGHE

8407
05:17:52,289 --> 05:17:53,591
YOU A COMPETITIVE PRICE.

8408
05:17:53,591 --> 05:17:55,292
SO IT'S A MUCH BIGGER PROBLEM

8409
05:17:55,292 --> 05:17:58,162
THAT REQUIRES THE FUNDERS, THE

8410
05:17:58,162 --> 05:18:01,665
GOVERNMENTS, ON THE GROUND AND

8411
05:18:01,665 --> 05:18:04,635
MOBILIZATION OF LARGER GROUP OF

8412
05:18:04,635 --> 05:18:05,069
PEOPLE.

8413
05:18:05,069 --> 05:18:06,170
AGAIN WITH THEM IT'S ABOUT

8414
05:18:06,170 --> 05:18:06,604
VOLUMES.

8415
05:18:06,604 --> 05:18:10,875
IF MORE PEOPLE ARE PIEI BUYING R

8416
05:18:10,875 --> 05:18:12,176
THEM LIKE FOR INSTANCE, IF WE'RE

8417
05:18:12,176 --> 05:18:13,310
COLLABORATING LIKE MY COLLEAGUE

8418
05:18:13,310 --> 05:18:16,013
SAID FROM UGANDA, ZAMBIA, SOUTH

8419
05:18:16,013 --> 05:18:17,782
AFRICA, WE'RE ALL DOING SIMILAR

8420
05:18:17,782 --> 05:18:19,750
RESEARCH, WE CAN NEGOTIATE UP

8421
05:18:19,750 --> 05:18:20,751
FRONT WITH A COMPANY TO LOWER

8422
05:18:20,751 --> 05:18:22,186
THE COST BECAUSE WE CAN

8423
05:18:22,186 --> 05:18:22,787
GUARANTEE BUSINESS BECAUSE WE

8424
05:18:22,787 --> 05:18:23,721
KNOW WE ARE FUNDING AND WE'RE

8425
05:18:23,721 --> 05:18:27,758
GOING TO BE BUYING CONSTANTLY

8426
05:18:27,758 --> 05:18:28,325
FROM THEM.

8427
05:18:28,325 --> 05:18:29,026
SO THAT'S SOMETHING THAT HAS

8428
05:18:29,026 --> 05:18:30,127
BEEN IDENTIFIED AND SOLUTION

8429
05:18:30,127 --> 05:18:30,961
NEEDS TO BE FOUND.

8430
05:18:30,961 --> 05:18:32,596
IF WE'RE GOING TO HAVE

8431
05:18:32,596 --> 05:18:33,697
MEANINGFUL BASIC SCIENCE

8432
05:18:33,697 --> 05:18:35,132
RESEARCH ON THE CONTINENT, WE

8433
05:18:35,132 --> 05:18:36,367
NEED TO FIND A WAY TO LOWER THE

8434
05:18:36,367 --> 05:18:37,668
COST OF DOING BUSINESS ON THE

8435
05:18:37,668 --> 05:18:37,935
CONTINENT.

8436
05:18:37,935 --> 05:18:41,405
>> A SMALL FOLLOW-UP, HAVE
YOU

8437
05:18:41,405 --> 05:18:44,108
THOUGHT OF APPROACHING INDIAN

8438
05:18:44,108 --> 05:18:45,976
LABORATORIES WHERE THEY MIGHT

8439
05:18:45,976 --> 05:18:48,813
HAVE ACCESS TO THESE RESOURCES

8440
05:18:48,813 --> 05:18:50,247
AND CAN MAYBE PROVIDE IT FOR

8441
05:18:50,247 --> 05:18:53,651
CHEAPER?

8442
05:18:53,651 --> 05:18:55,085
BECAUSE I DON'T SEE A LOT OF

8443
05:18:55,085 --> 05:18:57,021
REPRESENTATION OF INDIAN COHORTS

8444
05:18:57,021 --> 05:18:58,189
IN MOST OF THE STUDIES AND I

8445
05:18:58,189 --> 05:18:59,256
WOULD LIKE TO BRING UP THAT

8446
05:18:59,256 --> 05:19:00,124
CONVERSATION TOO.

8447
05:19:00,124 --> 05:19:03,327
THANKS A LOT FOR YOUR ANSWER.

8448
05:19:03,327 --> 05:19:05,563
>> LET'S MOVE THIS
FORWARD.

8449
05:19:05,563 --> 05:19:07,498
I WILL JUST MAKE THE COMMENT

8450
05:19:07,498 --> 05:19:10,734
THAT THIS RESOURCE ABOUT THE

8451
05:19:10,734 --> 05:19:13,370
REAGENTS AND OTHER THINGS WAS

8452
05:19:13,370 --> 05:19:16,974
THE BIGGEST OBSTACLE FOR ARVs

8453
05:19:16,974 --> 05:19:20,811
COMING TO AFRICA.

8454
05:19:20,811 --> 05:19:23,547
BUT THE CLINTON FOUNDATION, THE

8455
05:19:23,547 --> 05:19:26,851
U.N., UN AIDS, WHO, NIH, THERE

8456
05:19:26,851 --> 05:19:30,321
WERE LOTS OF EFFORTS WHERE THEY

8457
05:19:30,321 --> 05:19:32,189
CAME TOGETHER.

8458
05:19:32,189 --> 05:19:34,592
SO MAYBE WE CAN USE THAT AS A

8459
05:19:34,592 --> 05:19:36,694
PARADIGM GOING FORWARD, BUT I

8460
05:19:36,694 --> 05:19:41,298
THINK BTHANK BOTH QUESTIONERS O.

8461
05:19:41,298 --> 05:19:41,499
NEXT.

8462
05:19:41,499 --> 05:19:42,533
>> THANK YOU FOR THIS
PANEL.

8463
05:19:42,533 --> 05:19:44,735
THIS IS A REALLY CRITICAL TOPIC

8464
05:19:44,735 --> 05:19:45,069
FOR ALL OF US.

8465
05:19:45,069 --> 05:19:46,136
I THINK WE'VE BEEN TALKING ABOUT

8466
05:19:46,136 --> 05:19:48,272
HOW TO ENGAGE A GLOBAL EFFORT IN

8467
05:19:48,272 --> 05:19:49,640
HIV RESEARCH FOR A LONG TIME.

8468
05:19:49,640 --> 05:19:51,175
BUT I WOULD MAKE TWO POINTS.

8469
05:19:51,175 --> 05:19:53,143
ONE, I WOULD SORT OF -- I WANT

8470
05:19:53,143 --> 05:19:55,980
TO AGREE THAT RESOURCES IS A

8471
05:19:55,980 --> 05:19:59,817
MAJOR DRIVER FOR ENGAGEMENT.

8472
05:19:59,817 --> 05:20:01,785
AND 20 YEARS AGO WITH THE ONSET

8473
05:20:01,785 --> 05:20:03,621
OF THE CPRA PROGRAM, I THINK

8474
05:20:03,621 --> 05:20:05,422
THAT WAS A REALLY VISIONARY

8475
05:20:05,422 --> 05:20:06,857
INVESTMENT ON INFRASTRUCTURE AND

8476
05:20:06,857 --> 05:20:08,492
TRAINING THAT LED TO TRIALS AND

8477
05:20:08,492 --> 05:20:10,027
EVEN TODAY WE'RE STILL USING

8478
05:20:10,027 --> 05:20:11,562
SAMPLES FROM THAT PROGRAM THAT

8479
05:20:11,562 --> 05:20:13,097
LED TO LEADERSHIP GROWTH, THAT

8480
05:20:13,097 --> 05:20:16,634
LED TO NETWORKS, WHERE THAT WERE

8481
05:20:16,634 --> 05:20:18,636
EVENTUALLY PICKED UP BY THE ACTG

8482
05:20:18,636 --> 05:20:20,471
AND I THINK MAYBE IT'S TIME THAT

8483
05:20:20,471 --> 05:20:22,072
WE REVISIT THAT INVESTMENT AGAIN

8484
05:20:22,072 --> 05:20:23,674
IN CURE CENTERS OF RESEARCH

8485
05:20:23,674 --> 05:20:25,209
GLOBALLY.

8486
05:20:25,209 --> 05:20:28,078
AND MAYBE INFUSE RESOURCES FOR

8487
05:20:28,078 --> 05:20:29,780
THE PURPOSES OF ACHIEVING WHAT

8488
05:20:29,780 --> 05:20:33,417
WE ALL WANT, WHICH IS A GLOBAL

8489
05:20:33,417 --> 05:20:34,051
ENGAGEMENT.

8490
05:20:34,051 --> 05:20:35,586
THE SECOND POINT, I'VE BEEN IN

8491
05:20:35,586 --> 05:20:36,987
STUDY SECTION FOR 25 YEARS AND

8492
05:20:36,987 --> 05:20:38,289
I'VE SEEN MANY APPLICATIONS AS

8493
05:20:38,289 --> 05:20:39,557
ALREADY NOTED THAT ARE NOT

8494
05:20:39,557 --> 05:20:40,958
COMPETITIVE BECAUSE THESE STUDY

8495
05:20:40,958 --> 05:20:44,828
SECTION MEMBERS ARE NOT AS AWARE

8496
05:20:44,828 --> 05:20:46,564
OF THE OBJECTIVES OF A GLOBAL

8497
05:20:46,564 --> 05:20:47,464
ENGAGEMENT MISSION.

8498
05:20:47,464 --> 05:20:50,301
SO IF THERE'S GOING TO BE

8499
05:20:50,301 --> 05:20:52,503
INVESTMENTS IN GLOBAL

8500
05:20:52,503 --> 05:20:57,207
ENGAGEMENT, WE REALLY NEED TO

8501
05:20:57,207 --> 05:20:58,409
EMPHASIZE SPECIAL PANELS THAT

8502
05:20:58,409 --> 05:21:00,511
BRING EMPHASIS FROM THE GLOBAL

8503
05:21:00,511 --> 05:21:01,845
ENVIRONMENT TO THAT REVIEW

8504
05:21:01,845 --> 05:21:02,813
SESSION BECAUSE I THINK THAT MAY

8505
05:21:02,813 --> 05:21:04,381
ALSO BE A VERY DIRECT WAY TO

8506
05:21:04,381 --> 05:21:06,250
MAKE SURE THAT THE CREDITS OF

8507
05:21:06,250 --> 05:21:07,785
THE APPLICATIONS ARE DISCUSSED

8508
05:21:07,785 --> 05:21:10,721
WITHIN THE CONTEXT OF THEIR

8509
05:21:10,721 --> 05:21:11,822
ENVIRONMENTS AND THAT'S

8510
05:21:11,822 --> 05:21:12,656
SOMETHING TO CONSIDER.

8511
05:21:12,656 --> 05:21:20,864
THANK YOU.

8512
05:21:20,864 --> 05:21:22,633
>> EXCELLENT COMMENT, AND
I SEE

8513
05:21:22,633 --> 05:21:24,034
KARL MAKING NOTES.

8514
05:21:24,034 --> 05:21:24,501
NEXT, DEBBIE.

8515
05:21:24,501 --> 05:21:26,003
>> I HAD ACTUALLY A
QUESTION AND

8516
05:21:26,003 --> 05:21:27,538
A SIMILAR COMMENT AND THEN SOME

8517
05:21:27,538 --> 05:21:29,306
CONSIDERATION.

8518
05:21:29,306 --> 05:21:31,175
SO HANEEFA THANK YOU FOR LEADING

8519
05:21:31,175 --> 05:21:32,142
THIS EFFORT.

8520
05:21:32,142 --> 05:21:34,144
YOU USED THE WORD SMALL MONEYS

8521
05:21:34,144 --> 05:21:35,946
AND I THINK WHEN WE HAD INTERNAL

8522
05:21:35,946 --> 05:21:36,880
CONVERSATIONS ABOUT WHAT MONEY

8523
05:21:36,880 --> 05:21:38,115
SHOULD BE IN TERMS OF INVESTMENT

8524
05:21:38,115 --> 05:21:40,618
IN A GIVEN INDIVIDUAL.

8525
05:21:40,618 --> 05:21:42,453
WHAT I RECALL, THERE WAS A

8526
05:21:42,453 --> 05:21:44,254
SIZABLE AMOUNT, SO AN

8527
05:21:44,254 --> 05:21:45,356
INVESTIGATOR -- A MID CAREER

8528
05:21:45,356 --> 05:21:47,758
LEVEL INVESTIGATOR COULD HAVE A

8529
05:21:47,758 --> 05:21:49,560
REASONABLE AMOUNT OF MONEY.

8530
05:21:49,560 --> 05:21:50,661
IT'S STILL NOT SUFFICIENT, BUT

8531
05:21:50,661 --> 05:21:51,862
TO AT LEAST GET STARTED.

8532
05:21:51,862 --> 05:21:53,497
SO I THINK IT WOULD BE IMPORTANT

8533
05:21:53,497 --> 05:21:55,666
TO CLARIFY WHAT THAT DOLLAR

8534
05:21:55,666 --> 05:21:57,768
AMOUNT IS AS WE THINK ABOUT AN

8535
05:21:57,768 --> 05:21:58,869
APPLICATION AND THE GOALS.

8536
05:21:58,869 --> 05:22:01,905
AND SECONDLY, YOU KNOW, IN

8537
05:22:01,905 --> 05:22:04,375
WORKING WITH OUR COLLEAGUES IN

8538
05:22:04,375 --> 05:22:07,311
AFRICA, AND APPLYING FOR GRANTS,

8539
05:22:07,311 --> 05:22:09,546
EXACTLY WHAT WAS SAID, THE BAR

8540
05:22:09,546 --> 05:22:11,382
AND THE ASSESSMENT FOR RANKING

8541
05:22:11,382 --> 05:22:14,118
APPLICATIONS IS SO HIGH THAT OUR

8542
05:22:14,118 --> 05:22:16,387
AFRICAN COLLEAGUES GET VERY

8543
05:22:16,387 --> 05:22:17,488
DISCOURAGED WHEN A SMALL

8544
05:22:17,488 --> 05:22:18,522
APPLICATION IS TURNED DOWN.

8545
05:22:18,522 --> 05:22:21,625
SO I THINK WE NEED TO KIND OF

8546
05:22:21,625 --> 05:22:24,928
THINK THROUGH A FRAMEWORK FOR

8547
05:22:24,928 --> 05:22:25,996
SUCCESS OF THIS PROGRAM INSTEAD

8548
05:22:25,996 --> 05:22:28,332
OF THIS SORT OF CONVENTIONAL WAY

8549
05:22:28,332 --> 05:22:29,566
OF YOU SUBMIT YOUR APPLICATION

8550
05:22:29,566 --> 05:22:30,934
AND WHAT'S THE SCIENCE BUT

8551
05:22:30,934 --> 05:22:33,170
REALLY DO YOU HAVE THE RIGHT

8552
05:22:33,170 --> 05:22:34,138
MENTORSHIP ENVIRONMENT, IS THIS

8553
05:22:34,138 --> 05:22:35,239
PERSON GOING TO REALLY -- IS

8554
05:22:35,239 --> 05:22:37,174
THIS A TRUE INVESTMENT, OR JUST

8555
05:22:37,174 --> 05:22:39,576
WE'RE GOING TO DO THIS FOR THIS

8556
05:22:39,576 --> 05:22:40,244
INDIVIDUAL, AND I WOULD

8557
05:22:40,244 --> 05:22:42,079
ENCOURAGE YOU TO REALLY THINK

8558
05:22:42,079 --> 05:22:46,283
THROUGH TWO LEVELS, SOMEONE

8559
05:22:46,283 --> 05:22:47,685
THAT'S ADVANCED AS IMMACULATE IN

8560
05:22:47,685 --> 05:22:49,286
TERMS OF BEING ABLE TO GET

8561
05:22:49,286 --> 05:22:51,221
SIGNIFICANT FUNDING BUT THINK

8562
05:22:51,221 --> 05:22:52,656
ABOUT THE YOUNG PEOPLE, THE

8563
05:22:52,656 --> 05:22:54,525
EARLY INVESTIGATORS, I GET

8564
05:22:54,525 --> 05:22:55,592
REACHED OUT ALL THE TIME, I WANT

8565
05:22:55,592 --> 05:22:56,960
TO GET INVOLVED IN CURE

8566
05:22:56,960 --> 05:22:58,162
RESEARCH, HOW CAN I GET FUNDED

8567
05:22:58,162 --> 05:22:59,463
AND THERE'S REALLY NO MECHANISM

8568
05:22:59,463 --> 05:23:01,165
TO GET SOMEONE STARTED.

8569
05:23:01,165 --> 05:23:03,567
SO THINKING THROUGH A TWO-TIER

8570
05:23:03,567 --> 05:23:05,736
PROCESS SO YOU HAVE A CONTINUOUS

8571
05:23:05,736 --> 05:23:07,071
PIPELINE TO KEEP THAT GROWING.

8572
05:23:07,071 --> 05:23:09,173
AND THEN MY THIRD FOR

8573
05:23:09,173 --> 05:23:16,113
CONSIDERATIONS IS, ZAZA AND --

8574
05:23:16,113 --> 05:23:17,347
EXCELLENT LABORATORIES, AND AS

8575
05:23:17,347 --> 05:23:19,283
TOM SAID A LOT OF THE

8576
05:23:19,283 --> 05:23:19,717
COLLABORATORIES HAVE

8577
05:23:19,717 --> 05:23:21,151
INVESTIGATORS IN

8578
05:23:21,151 --> 05:23:21,819
RESOURCE-CONSTRAINED SETTINGS,

8579
05:23:21,819 --> 05:23:23,420
SO WHY DON'T WE START WITH WHERE

8580
05:23:23,420 --> 05:23:24,488
THE INFRASTRUCTURE EXISTS TO

8581
05:23:24,488 --> 05:23:28,058
MAKE THE PROGRAM SUCCESSFUL IN

8582
05:23:28,058 --> 05:23:28,759
ITS FIRST ROUND.

8583
05:23:28,759 --> 05:23:31,495
THAT'S JUST FOR CONSIDERATION.

8584
05:23:31,495 --> 05:23:33,497
>> THAT'S WHERE SOUTH TO
SOUTH

8585
05:23:33,497 --> 05:23:35,632
COLLABORATION CAN REALLY TAKE

8586
05:23:35,632 --> 05:23:36,734
OFF.

8587
05:23:36,734 --> 05:23:37,835
ESTABLISH A COUPLE CENTERS OF

8588
05:23:37,835 --> 05:23:41,004
EXCELLENCE IN CURE RESEARCH WITH

8589
05:23:41,004 --> 05:23:42,573
AFRICAN INVESTIGATORS AT THE

8590
05:23:42,573 --> 05:23:44,975
LEAD, AND THEN DO SOUTH TO SOUTH

8591
05:23:44,975 --> 05:23:48,178
WITHIN THE CONTINENT.

8592
05:23:48,178 --> 05:23:48,579
, I THINK

8593
05:23:48,579 --> 05:23:49,780
WOULD BE A GREAT WAY.

8594
05:23:49,780 --> 05:23:51,248
I WISH THERE WAS A LOT MORE TIME

8595
05:23:51,248 --> 05:23:53,383
BECAUSE WE COULD ASK YOU ABOUT

8596
05:23:53,383 --> 05:23:55,018
YOUR EXPERIENCE WITH IMPACT AND

8597
05:23:55,018 --> 05:23:57,955
HOW WELL THAT FUNCTIONED WITHIN

8598
05:23:57,955 --> 05:23:59,256
AFRICA AND SOME OF THE STUDIES

8599
05:23:59,256 --> 05:24:01,258
THAT YOU PRESENTED EARLIER.

8600
05:24:01,258 --> 05:24:02,826
BUT WE'LL SAVE THAT TO

8601
05:24:02,826 --> 05:24:03,727
AFTERWARDS, DEBBIE.

8602
05:24:03,727 --> 05:24:06,764
I'LL SEE HER BACK IN BALTIMORE.

8603
05:24:06,764 --> 05:24:07,231
NEXT.

8604
05:24:07,231 --> 05:24:09,566
>> YES, HELLO.

8605
05:24:09,566 --> 05:24:12,636
THANK YOU FOR BEING HERE.

8606
05:24:12,636 --> 05:24:16,073
I'M A COMMUNITY REPRESENTATIVE

8607
05:24:16,073 --> 05:24:19,042
OF THE REACH COLLABORATORY IN

8608
05:24:19,042 --> 05:24:20,677
NEW YORK.

8609
05:24:20,677 --> 05:24:22,045
FIRST I WOULD LIKE TO REMIND

8610
05:24:22,045 --> 05:24:24,381
EVERYBODY THAT THE REACH

8611
05:24:24,381 --> 05:24:27,017
COLLABORATORY ASSISTED THE RAKAI

8612
05:24:27,017 --> 05:24:30,354
HEALTH SCIENCE PROGRAM WITH

8613
05:24:30,354 --> 05:24:34,057
INSTALLATION OF A NEW DDPCR.

8614
05:24:34,057 --> 05:24:35,159
THIS IS PERHAPS AT THE BEGINNING

8615
05:24:35,159 --> 05:24:38,695
OF SOME KIND OF A MORE CLOSE

8616
05:24:38,695 --> 05:24:40,731
COLLABORATION, TECHNICAL

8617
05:24:40,731 --> 05:24:41,832
ASSISTANCE, WHATEVER -- HOWEVER

8618
05:24:41,832 --> 05:24:44,601
WE NEED TO GO.

8619
05:24:44,601 --> 05:24:45,769
I'M A COMMUNITY REPRESENTATIVE

8620
05:24:45,769 --> 05:24:48,105
AND I KNOW AND I REMEMBER THAT

8621
05:24:48,105 --> 05:24:50,707
HIV HAS BEEN IDENTIFIED ABOUT 40

8622
05:24:50,707 --> 05:24:56,847
YEARS AGO I WOULD LIKE TO KNOW

8623
05:24:56,847 --> 05:24:57,915
AS A COMMUNITY REPRESENTATIVE,

8624
05:24:57,915 --> 05:25:01,385
HOW DOES THE COMMUNITY FEEL

8625
05:25:01,385 --> 05:25:07,958
ABOUT CURE?

8626
05:25:07,958 --> 05:25:12,095
IN YOUR COMMUNITIES, --

8627
05:25:12,095 --> 05:25:14,998
EXTENDING RESEARCH AND CLINICAL

8628
05:25:14,998 --> 05:25:22,906
TRIALS HELP POPULARIZE HIV CURE

8629
05:25:22,906 --> 05:25:24,174
AND WOULD THE PEOPLE IN YOUR

8630
05:25:24,174 --> 05:25:25,843
COMMUNITIES PARTICIPATE?

8631
05:25:25,843 --> 05:25:27,010
>> ELINA, CAN YOU ADDRESS
THAT,

8632
05:25:27,010 --> 05:25:28,979
PLEASE?

8633
05:25:28,979 --> 05:25:34,218
GREAT QUESTION.

8634
05:25:34,218 --> 05:25:38,355
>> I THINK IT EXTENDS TO
WHAT'S

8635
05:25:38,355 --> 05:25:40,490
THE REACH ON THE GROUND IN THE

8636
05:25:40,490 --> 05:25:41,191
HIV CURE RESEARCH.

8637
05:25:41,191 --> 05:25:43,293
I THINK WHEN WE BRING OUT THAT

8638
05:25:43,293 --> 05:25:43,994
UNDERSTANDING, THAT'S WHERE WE

8639
05:25:43,994 --> 05:25:45,362
START TO DEFINE.

8640
05:25:45,362 --> 05:25:47,497
I KNOW WE COME TO UNDERSTAND OF

8641
05:25:47,497 --> 05:25:49,333
THE DIFFERENT STRATEGIES ON CURE

8642
05:25:49,333 --> 05:25:51,001
RESEARCH THAT ARE THERE, BUT I

8643
05:25:51,001 --> 05:25:54,271
THINK WHAT WE BRING TO THE

8644
05:25:54,271 --> 05:25:55,572
COMMUNITY TO GO OVER JUST THE

8645
05:25:55,572 --> 05:25:57,908
SENSE BUT I THINK WE ATTACH IN

8646
05:25:57,908 --> 05:25:59,643
REAL LIFE STORIES, AND I THINK

8647
05:25:59,643 --> 05:26:00,644
WE EXPLAIN THAT, THAT'S WHEN I

8648
05:26:00,644 --> 05:26:02,646
THINK WE'RE LOOKING INTO THE

8649
05:26:02,646 --> 05:26:05,849
COMPONENT OF IF YOU'RE ABLE

8650
05:26:05,849 --> 05:26:07,818
TO -- WE'RE STARTING WITH THE

8651
05:26:07,818 --> 05:26:09,253
BASIC -- DOES IT GO TO YOU AND

8652
05:26:09,253 --> 05:26:10,287
WE UNDERSTAND YOU CANNOT

8653
05:26:10,287 --> 05:26:11,989
TRANSMIT AND THEN YOU'RE

8654
05:26:11,989 --> 05:26:13,223
STARTING TO BRING IN THE

8655
05:26:13,223 --> 05:26:18,161
DEFINITION OF CURE AND STAGE SO

8656
05:26:18,161 --> 05:26:19,563
I THINK IT BRINGS IN A DIFFERENT

8657
05:26:19,563 --> 05:26:20,597
CONTEXT AND DIFFERENT BACKGROUND

8658
05:26:20,597 --> 05:26:24,468
OF THE COMMUNITIES, AND ENGAGING

8659
05:26:24,468 --> 05:26:25,402
THE COMMUNITIES, I THINK IT'S

8660
05:26:25,402 --> 05:26:29,139
ABOUT STARTING FROM STEP ONE.

8661
05:26:29,139 --> 05:26:33,710
SO WE MOVE -- I HEARD -- WITH

8662
05:26:33,710 --> 05:26:35,579
THE COMMUNITY THAT THERE'S

8663
05:26:35,579 --> 05:26:36,413
INFORMATION TO MAKE SURE THE

8664
05:26:36,413 --> 05:26:37,748
COMMUNITIES ARE FULLY ENGAGED AS

8665
05:26:37,748 --> 05:26:40,384
WELL AS TO ADVOCATE.

8666
05:26:40,384 --> 05:26:50,627
>> THANK YOU.

8667
05:26:51,628 --> 05:26:53,363
>> MY FAMILY HAS
PARTICIPATED IN

8668
05:26:53,363 --> 05:26:56,233
THIS COHORT FOR 30-SOMETHING

8669
05:26:56,233 --> 05:27:04,174
YEARS.

8670
05:27:04,174 --> 05:27:05,609
THIS IS THEIR HOPE, WHAT SOMEONE

8671
05:27:05,609 --> 05:27:06,977
TOLD ME.

8672
05:27:06,977 --> 05:27:08,745
THEY BELIEVE BY GIVING THEIR

8673
05:27:08,745 --> 05:27:12,449
BLOOD, EVERY TIME, SOMETHING

8674
05:27:12,449 --> 05:27:13,517
GOOD EVENTUALLY WILL COME OUT OF

8675
05:27:13,517 --> 05:27:17,054
THIS.

8676
05:27:17,054 --> 05:27:18,188
THAT'S THE BIGGEST MOTIVATOR FOR

8677
05:27:18,188 --> 05:27:21,892
THEM TO KEEP DOING THIS.

8678
05:27:21,892 --> 05:27:25,095
>> THANK YOU.

8679
05:27:25,095 --> 05:27:26,363
>> WE NEED TO MOVE ON.

8680
05:27:26,363 --> 05:27:27,397
>> THANK YOU SO MUCH.

8681
05:27:27,397 --> 05:27:31,568
THIS IS JUST A COMMENT, COMING

8682
05:27:31,568 --> 05:27:33,236
FROM WHAT I SEE IN MY COUNTRY,

8683
05:27:33,236 --> 05:27:34,504
THAT'S UGANDA, IS THAT I THINK

8684
05:27:34,504 --> 05:27:36,940
THERE IS NEED FOR US IN AFRICA

8685
05:27:36,940 --> 05:27:39,109
AS WELL TO COME UP WITH, I DON'T

8686
05:27:39,109 --> 05:27:41,745
KNOW, MAYBE LIKE A CONTINENTAL

8687
05:27:41,745 --> 05:27:43,146
ANALYSIS OF WHAT IS ACTUALLY --

8688
05:27:43,146 --> 05:27:46,049
WHAT IS THIS TRICK THAT WE HAVE

8689
05:27:46,049 --> 05:27:48,552
AS A -- COUNTRY IN TERMS OF HIV

8690
05:27:48,552 --> 05:27:50,087
CURE RESEARCH, WHAT ARE OUR

8691
05:27:50,087 --> 05:27:54,391
WEAKNESSES, BECAUSE I FEEL LIKE

8692
05:27:54,391 --> 05:27:56,360
SOMETIMES WHEN WE LOOK AT A

8693
05:27:56,360 --> 05:27:57,461
COUNTRY, INSTITUTIONS ARE ALL

8694
05:27:57,461 --> 05:27:58,228
DOING DIFFERENT THINGS, THEY

8695
05:27:58,228 --> 05:28:00,897
HAVE PROBABLY DIFFERENT -- AND

8696
05:28:00,897 --> 05:28:02,366
THEY HAVE PROBABLY DIFFERENT

8697
05:28:02,366 --> 05:28:04,835
MACHINE, SO HOW TO ENSURE THAT

8698
05:28:04,835 --> 05:28:07,637
ALL OUR RESEARCHERS IN A COUNTRY

8699
05:28:07,637 --> 05:28:08,939
KNOW WHAT IS HAPPENING AT

8700
05:28:08,939 --> 05:28:10,507
INSTITUTION A SO THAT WHEN THEY

8701
05:28:10,507 --> 05:28:11,708
NEED ANYTHING, THEY CAN EASILY

8702
05:28:11,708 --> 05:28:13,176
GO THERE AND THEY DON'T HAVE TO

8703
05:28:13,176 --> 05:28:15,145
DUPLICATE OR EVEN FIND MORE

8704
05:28:15,145 --> 05:28:17,948
EXPENSES AND ALL THAT, SO MAYBE

8705
05:28:17,948 --> 05:28:19,716
AS COUNTRIES, WE HAVE TO LOOK AT

8706
05:28:19,716 --> 05:28:22,319
LIKE MAYBE LIKE INSTITUTIONAL

8707
05:28:22,319 --> 05:28:23,720
SORT ANALYSIS AND THEN THAT CAN

8708
05:28:23,720 --> 05:28:25,155
COME UP TO COUNTRY AND THEN

8709
05:28:25,155 --> 05:28:27,491
MAYBE IT CAN EVEN COME UP TO THE

8710
05:28:27,491 --> 05:28:27,758
CONTINENT.

8711
05:28:27,758 --> 05:28:29,860
AND THEN ALSO I JUST WANT TO

8712
05:28:29,860 --> 05:28:31,595
MAKE A COMMENT ON WHAT THE

8713
05:28:31,595 --> 05:28:34,931
COMMUNITY THINKS ABOUT HIV CURE.

8714
05:28:34,931 --> 05:28:36,633
IT IS DIFFERENT ACCORDING TO

8715
05:28:36,633 --> 05:28:37,334
EACH.

8716
05:28:37,334 --> 05:28:39,002
MY MOTHER WOULD WANT AN HIV CURE

8717
05:28:39,002 --> 05:28:40,237
BECAUSE SHE'S CURRENTLY HAVING A

8718
05:28:40,237 --> 05:28:42,105
HEART DISEASE, SO PROBABLY THOSE

8719
05:28:42,105 --> 05:28:45,108
ISSUES OF HEART FAILURE, LIVER

8720
05:28:45,108 --> 05:28:46,276
FAILURE AND ALL THAT ARE GIVING

8721
05:28:46,276 --> 05:28:48,745
HER MORE REASON FOR AN HIV CURE.

8722
05:28:48,745 --> 05:28:50,113
I WANT AN HIV CURE BECAUSE I'M

8723
05:28:50,113 --> 05:28:51,014
TIRED OF MEDICATION.

8724
05:28:51,014 --> 05:28:54,551
SO I THINK THE REASONS ACCORDING

8725
05:28:54,551 --> 05:28:56,887
TO AGE OR SEX ARE DIFFERENT.

8726
05:28:56,887 --> 05:28:57,888
THANK YOU.

8727
05:28:57,888 --> 05:28:59,723
>> I'VE GOT TO ASK, ZAZA,
DO YOU

8728
05:28:59,723 --> 05:29:01,792
WANT TO COMMENT ON THAT?

8729
05:29:01,792 --> 05:29:04,694
MAYBE IMMACULATE?

8730
05:29:04,694 --> 05:29:06,229
>> I THINK A QUICK COMMENT
ON

8731
05:29:06,229 --> 05:29:07,431
THAT.

8732
05:29:07,431 --> 05:29:11,334
IT'S VERY, VERY TRUE THAT

8733
05:29:11,334 --> 05:29:15,138
RESEARCH EVERYWHERE IS SILOED.

8734
05:29:15,138 --> 05:29:16,606
INCLUDING HERE IN THE U.S.

8735
05:29:16,606 --> 05:29:19,142
IN AFRICA IT'S EVEN MORE SILOED

8736
05:29:19,142 --> 05:29:20,911
BECAUSE YOU ARE ONLY ALIGNED

8737
05:29:20,911 --> 05:29:21,978
WITH PEOPLE THAT YOU WORK WITH

8738
05:29:21,978 --> 05:29:22,913
AND WHERE YOU'RE GETTING YOUR

8739
05:29:22,913 --> 05:29:25,982
FUNDING TO DO YOUR RESEARCH, AND

8740
05:29:25,982 --> 05:29:27,184
MOSTLY YOU'LL FIND THAT THE

8741
05:29:27,184 --> 05:29:29,820
PEOPLE THAT YOU ARE WORKING WITH

8742
05:29:29,820 --> 05:29:31,054
TO FUND YOUR RESEARCH WHO ARE

8743
05:29:31,054 --> 05:29:32,389
HELPING YOU ARE PEOPLE FROM

8744
05:29:32,389 --> 05:29:33,523
THE -- AND THOSE ARE THE PEOPLE

8745
05:29:33,523 --> 05:29:34,591
YOU INTERACT WITH.

8746
05:29:34,591 --> 05:29:36,593
BUT THERE IS NEED LIKE YOU SAY

8747
05:29:36,593 --> 05:29:38,261
TO HAVE SOUTH TO SOUTH

8748
05:29:38,261 --> 05:29:38,728
COLLABORATION.

8749
05:29:38,728 --> 05:29:39,930
SO HOW DO WE DO THAT?

8750
05:29:39,930 --> 05:29:41,965
WE NEED TO INCENTIVIZE THAT.

8751
05:29:41,965 --> 05:29:44,868
THE ONLY WAY YOU CAN I INCENTIVE

8752
05:29:44,868 --> 05:29:48,438
THAT IS SAY YOU FUND AN AFRICAN

8753
05:29:48,438 --> 05:29:48,772
COLLABORATORY.

8754
05:29:48,772 --> 05:29:52,542
AND THOSE PEOPLE ARE FORCED TO

8755
05:29:52,542 --> 05:29:53,577
WORK TOGETHER BECAUSE EVERYONE

8756
05:29:53,577 --> 05:29:56,113
NOW HAS A SKIN IN THE GAME.

8757
05:29:56,113 --> 05:29:57,380
THE NEED TO DELIVER ON THE

8758
05:29:57,380 --> 05:29:58,615
OBJECTIVES OF THE STUDY AND THEN

8759
05:29:58,615 --> 05:30:01,184
YOU'LL FIND WHO HAS STRENGTH IN

8760
05:30:01,184 --> 05:30:02,752
COHORT FORMULATION, WHO HAS

8761
05:30:02,752 --> 05:30:04,955
STRENGTH IN RESERVOIR ASSAYS,

8762
05:30:04,955 --> 05:30:06,823
WHO HAS STRENGTH IN IMMUNOLOGY,

8763
05:30:06,823 --> 05:30:08,358
CAN WE ALL COME TOGETHER, AND

8764
05:30:08,358 --> 05:30:09,392
PEOPLE BEGIN TO TALK TO EACH

8765
05:30:09,392 --> 05:30:11,228
OTHER, THE STUDENTS NEED TO

8766
05:30:11,228 --> 05:30:13,029
INTERACT AND NEED TO WORK AS A

8767
05:30:13,029 --> 05:30:15,532
TEAM AND FOR ME, THAT'S THE WAY

8768
05:30:15,532 --> 05:30:16,199
FORWARD.

8769
05:30:16,199 --> 05:30:19,136
IF THERE IS FUNDING MODALITIES

8770
05:30:19,136 --> 05:30:22,272
THAT ATTRACT -- FORCES PEOPLE TO

8771
05:30:22,272 --> 05:30:24,141
WORK TOGETHER TO SAY YOU NEED TO

8772
05:30:24,141 --> 05:30:26,776
COME TOGETHER AND YOU ARE MORE

8773
05:30:26,776 --> 05:30:28,545
LIKELY TO GET THIS FUNDING IF

8774
05:30:28,545 --> 05:30:33,183
YOU ACTUALLY BAND TOGETHER AS

8775
05:30:33,183 --> 05:30:34,050
AFRICAN INVESTIGATORS, I THINK

8776
05:30:34,050 --> 05:30:39,389
THAT WILL GET US SOMEWHERE.

8777
05:30:39,389 --> 05:30:42,392
SO MOSTLY IN SOUTH AFRICA,

8778
05:30:42,392 --> 05:30:44,628
WITHIN SOUTH AFRICA, PEOPLE

8779
05:30:44,628 --> 05:30:47,531
WORKING IN JOHANNESBURG DON'T

8780
05:30:47,531 --> 05:30:49,132
EVEN TALK TO PEOPLE WORKING IN

8781
05:30:49,132 --> 05:30:50,901
CAPETOWN, SO ON AND SO FORTH AND

8782
05:30:50,901 --> 05:30:53,136
THE SAME THING IN MALAWI, THE

8783
05:30:53,136 --> 05:30:54,271
SAME THING IN UGANDA.

8784
05:30:54,271 --> 05:30:55,605
IF WE CAN HAVE FUNDING THAT

8785
05:30:55,605 --> 05:30:57,774
ACTUALLY TRIES TO BREAK THOSE

8786
05:30:57,774 --> 05:31:00,377
SILOS, I THINK WE CAN MAKE

8787
05:31:00,377 --> 05:31:01,444
HEADWAY.

8788
05:31:01,444 --> 05:31:01,745
>> GREAT.

8789
05:31:01,745 --> 05:31:05,248
WE HAVE THREE PEOPLE AT THAT

8790
05:31:05,248 --> 05:31:05,615
MICROPHONE.

8791
05:31:05,615 --> 05:31:09,019
I'M GOING TO HAVE YOU EACH ASK

8792
05:31:09,019 --> 05:31:09,619
YOUR QUESTION.

8793
05:31:09,619 --> 05:31:11,221
LET'S GET ALL THREE QUESTIONS UP

8794
05:31:11,221 --> 05:31:12,389
BECAUSE THEN WE HAVE TO CLOSE

8795
05:31:12,389 --> 05:31:13,757
THE PANEL.

8796
05:31:13,757 --> 05:31:14,324
OR COMMENT.

8797
05:31:14,324 --> 05:31:15,292
DOESN'T HAVE TO BE A QUESTION.

8798
05:31:15,292 --> 05:31:17,360
>> I'LL TRY TO BE VERY
FAST.

8799
05:31:17,360 --> 05:31:19,329
I'M GUIN LEE FROM WHI WEILL COR.

8800
05:31:19,329 --> 05:31:20,964
SO I JUST WANT TO SHARE A STORY

8801
05:31:20,964 --> 05:31:22,899
MAYBE AND A PERSONAL EXPERIENCE

8802
05:31:22,899 --> 05:31:24,701
OF KNOWLEDGE TRANSFER, AND SO

8803
05:31:24,701 --> 05:31:31,508
I'M FUNDED BY AN R01 THAT

8804
05:31:31,508 --> 05:31:35,111
INVOLVES WORKING WITH A COHORT

8805
05:31:35,111 --> 05:31:39,883
IN UGANDA, AND SO I MADE SURE TO

8806
05:31:39,883 --> 05:31:41,818
WRITE IN A KNOWLEDGE TRANSFER

8807
05:31:41,818 --> 05:31:44,221
COMPONENT IN THE R01, IT'S MY

8808
05:31:44,221 --> 05:31:46,189
SOLO R01 SO NOT RELATED TO

8809
05:31:46,189 --> 05:31:48,091
REACH, BUT WRITING IN A

8810
05:31:48,091 --> 05:31:48,858
KNOWLEDGE TRANSFER COMPONENT IN

8811
05:31:48,858 --> 05:31:51,027
THE R01 SO NOW I'M CONNECTED TO

8812
05:31:51,027 --> 05:31:53,563
A MENTEE THERE, AND SO WE SET UP

8813
05:31:53,563 --> 05:31:54,898
WEEKLY MEETINGS, SO I WOULD TALK

8814
05:31:54,898 --> 05:31:57,200
TO THIS MENTEE EVERY WEEK AND I

8815
05:31:57,200 --> 05:31:58,435
WILL TEACH THE MENTEE HOW TO,

8816
05:31:58,435 --> 05:32:00,537
FOR EXAMPLE, USE GRAPH PRISSMM,

8817
05:32:00,537 --> 05:32:06,943
HOW TO, FOR EXAMPLE, USE  EXCEL,

8818
05:32:06,943 --> 05:32:10,647
BUT ALSO TO ANALYZE DATA SO DRY

8819
05:32:10,647 --> 05:32:11,448
ANALYTICAL SKILLS CAN BE PASSED

8820
05:32:11,448 --> 05:32:13,116
ON VIRTUALLY.

8821
05:32:13,116 --> 05:32:16,386
SO WE HAVE BEEN CONTINUING ON

8822
05:32:16,386 --> 05:32:20,857
WITH THO THOSE WEEKLY MEETINGS R

8823
05:32:20,857 --> 05:32:24,194
OVER A YEAR AND THE MENTEE HAS

8824
05:32:24,194 --> 05:32:27,464
SUCCESSFULLY PRODUCED -- SO

8825
05:32:27,464 --> 05:32:28,765
THESE ARE LITTLE THINGS WE CAN

8826
05:32:28,765 --> 05:32:29,933
DO TO TRANSFER THE KNOWLEDGE AND

8827
05:32:29,933 --> 05:32:31,601
IT DOESN'T HAVE TO BE WET LAB

8828
05:32:31,601 --> 05:32:33,737
AND REAGENT FOCUSED, JUST LITTLE

8829
05:32:33,737 --> 05:32:34,838
THINGS, A LITTLE AT A TIME, I

8830
05:32:34,838 --> 05:32:37,240
THINK.

8831
05:32:37,240 --> 05:32:39,743
THAT'S WHAT I WANT TO SHARE.

8832
05:32:39,743 --> 05:32:40,610
THANKS.

8833
05:32:40,610 --> 05:32:42,779
>> THANKS, GREAT PANEL.

8834
05:32:42,779 --> 05:32:45,815
I JUST HAVE A COMMENT.

8835
05:32:45,815 --> 05:32:48,051
I'M WEARING MY IAS HAT HERE AND

8836
05:32:48,051 --> 05:32:53,857
THAT IS WH I THINK THERE'S A NUF

8837
05:32:53,857 --> 05:32:55,191
SIMILAR EFFORTS.

8838
05:32:55,191 --> 05:32:57,227
BRILLIANT TO SEE GETTING BEHIND

8839
05:32:57,227 --> 05:32:59,629
FUNDING RESEARCH, SOME OTHER

8840
05:32:59,629 --> 05:33:01,031
EFFORTS OBVIOUSLY THROUGH THE

8841
05:33:01,031 --> 05:33:02,666
EIS AND TRAINING THROUGH THE

8842
05:33:02,666 --> 05:33:07,337
RESEARCH ACADEMIES AIDS FUND AND

8843
05:33:07,337 --> 05:33:09,039
GATES ARE ABOUT TO INVEST

8844
05:33:09,039 --> 05:33:12,409
HEAVILY IN ADVOCACY FOR CURE IN

8845
05:33:12,409 --> 05:33:14,077
AN AFRICAN-LED INITIATIVE

8846
05:33:14,077 --> 05:33:17,647
TOGETHER WITH AVAC AND IAS, AND

8847
05:33:17,647 --> 05:33:20,583
I THINK IN THE END WHAT WE WANT

8848
05:33:20,583 --> 05:33:22,886
IS AFRICAN-LED, AFRICAN-FUNDED

8849
05:33:22,886 --> 05:33:24,954
SCIENCE.

8850
05:33:24,954 --> 05:33:28,091
SO WE NEED A BIT OF MORE

8851
05:33:28,091 --> 05:33:30,293
COHERENT ADVOCACY VOICE WITH

8852
05:33:30,293 --> 05:33:31,761
FUNDERS AND LEADERS IN AFRICA,

8853
05:33:31,761 --> 05:33:33,797
AND I JUST WONDER WHETHER WE HAD

8854
05:33:33,797 --> 05:33:35,465
A BIT MORE COORDINATION AROUND

8855
05:33:35,465 --> 05:33:39,035
SOME OF THESE EFFORTS.

8856
05:33:39,035 --> 05:33:40,570
WE COULD GET TOGETHER A BIT OF

8857
05:33:40,570 --> 05:33:43,273
NARRATIVE FOR GREATER ADVOCACY

8858
05:33:43,273 --> 05:33:45,575
AND I'VE BEEN INVOLVED IN SOME

8859
05:33:45,575 --> 05:33:47,610
EFFORTS AIMED AT THIS, AND ONE

8860
05:33:47,610 --> 05:33:53,049
OF THOSE INVOLVED JOHN KANGESAN

8861
05:33:53,049 --> 05:33:54,884
BEFORE HE MOVED TO PEPFAR, IT

8862
05:33:54,884 --> 05:33:55,885
WAS JUST IN THE LAST TWO MONTHS

8863
05:33:55,885 --> 05:33:58,621
OF HIM AT THE AFRICAN CDC.

8864
05:33:58,621 --> 05:34:01,358
AND HE WAS VERY RECEPTIVE TO THE

8865
05:34:01,358 --> 05:34:03,526
WHOLE CONCEPT OF WHY CURE

8866
05:34:03,526 --> 05:34:05,829
RESEARCH NEEDS TO HAPPEN IN

8867
05:34:05,829 --> 05:34:10,300
AFRICA, WHY THERE NEEDS TO BE

8868
05:34:10,300 --> 05:34:11,134
KNOWLEDGE AMONGST THE

8869
05:34:11,134 --> 05:34:11,801
COMMUNITIES AND HE COULD ALSO

8870
05:34:11,801 --> 05:34:13,470
SEE THE ECONOMIC ARGUMENT FOR

8871
05:34:13,470 --> 05:34:17,307
LEADERS IN THE AFRICAN CONTINENT

8872
05:34:17,307 --> 05:34:19,109
TO INVEST IN THIS FOR THEMSELVES

8873
05:34:19,109 --> 05:34:19,542
ECONOMICALLY.

8874
05:34:19,542 --> 05:34:21,878
SO I THINK JOHN WOULD BE A

8875
05:34:21,878 --> 05:34:25,348
REALLY GOOD PERSON TO ENGAGE AS

8876
05:34:25,348 --> 05:34:28,184
BOTH FROM A PEPFAR POINT OF VIEW

8877
05:34:28,184 --> 05:34:30,186
AND KNOWLEDGE OF THE CDC AND IAS

8878
05:34:30,186 --> 05:34:31,554
CAN HELP PLAY A ROLE BUT I THINK

8879
05:34:31,554 --> 05:34:34,457
WE DO NEED A COORDINATED EFFORT

8880
05:34:34,457 --> 05:34:35,392
AROUND WHAT ARE THE NEEDS, WHAT

8881
05:34:35,392 --> 05:34:36,593
ARE THE CURRENT OPPORTUNITIES,

8882
05:34:36,593 --> 05:34:38,128
AND HOW ARE WE REALLY GOING TO

8883
05:34:38,128 --> 05:34:40,130
GET TO SOMETHING THAT'S

8884
05:34:40,130 --> 05:34:42,265
AFRICAN-LED AND FUNDED, AND A

8885
05:34:42,265 --> 05:34:45,168
WAY OF ENGAGING AFRICAN

8886
05:34:45,168 --> 05:34:45,502
LEADERSHIP.

8887
05:34:45,502 --> 05:34:49,506
AND THE START COULD BE CDC AND

8888
05:34:49,506 --> 05:34:55,745
PEPFAR.

8889
05:34:55,745 --> 05:34:57,013
>> GREAT COMMENT.

8890
05:34:57,013 --> 05:34:57,747
TOTALLY AGREE.

8891
05:34:57,747 --> 05:34:58,014
LAST ONE.

8892
05:34:58,014 --> 05:35:01,184
>> MY NAME IS JUSTINE FROM

8893
05:35:01,184 --> 05:35:01,451
UGANDA.

8894
05:35:01,451 --> 05:35:06,856
I WORK WITH THE -- PROJECT

8895
05:35:06,856 --> 05:35:10,026
MOSTLY COLLABORATING WITH THE

8896
05:35:10,026 --> 05:35:12,328
U.S. MHRP AND I WANTED TO JUST

8897
05:35:12,328 --> 05:35:14,898
TALK ABOUT THE TIME THAT WE

8898
05:35:14,898 --> 05:35:16,533
PROCESS THE LYMPH NODES AND

8899
05:35:16,533 --> 05:35:20,370
BIOPSIES FOR CURE RESEARCH, HIV,

8900
05:35:20,370 --> 05:35:22,772
AND FOR THE GUT BIOPSIES.

8901
05:35:22,772 --> 05:35:25,842
WHAT WE DID WITH STAINING THEM,

8902
05:35:25,842 --> 05:35:27,343
AND LOOKING AT THE DATA USING

8903
05:35:27,343 --> 05:35:31,781
THE FLOW CYTOMETERS, WE

8904
05:35:31,781 --> 05:35:32,916
DEMONSTRATED WE HAVE -- LIKE IT

8905
05:35:32,916 --> 05:35:36,686
IS VERY POSSIBLE TO CHARACTERIZE

8906
05:35:36,686 --> 05:35:41,591
REALTIME ET RESERVOIR IN LOW AND

8907
05:35:41,591 --> 05:35:45,795
MIDDLE INCOME COUNTRIES, SO

8908
05:35:45,795 --> 05:35:47,864
NEEDS WITHIN TRAINING RESOURCES,

8909
05:35:47,864 --> 05:35:49,732
ESPECIALLY GRANT-WRITING SKILLS,

8910
05:35:49,732 --> 05:35:52,368
AND THE RELEVANT EQUIPMENT.

8911
05:35:52,368 --> 05:35:56,639
THANK YOU.

8912
05:35:56,639 --> 05:35:59,309
>> THANK YOU.

8913
05:35:59,309 --> 05:35:59,576
[APPLAUSE]

8914
05:35:59,576 --> 05:36:02,045
>> WE'RE AT THE END OF OUR

8915
05:36:02,045 --> 05:36:05,648
ALLOTTED TIME, BUT I WANT TO SEE

8916
05:36:05,648 --> 05:36:07,283
IF ANY OF THE PANELISTS, BECAUSE

8917
05:36:07,283 --> 05:36:09,519
WE JUST HAD SOME COMMENTS, IF

8918
05:36:09,519 --> 05:36:11,054
ANY OF YOU VERY QUICKLY WANT TO

8919
05:36:11,054 --> 05:36:12,522
GIVE A FINAL WORD TO THIS

8920
05:36:12,522 --> 05:36:12,922
AUDIENCE?

8921
05:36:12,922 --> 05:36:13,957
YOU DON'T GET THIS OPPORTUNITY

8922
05:36:13,957 --> 05:36:18,261
VERY OFTEN.

8923
05:36:18,261 --> 05:36:23,600
SO ANYONE DOWN THE LINE.

8924
05:36:23,600 --> 05:36:25,034
EDWARD WANTS TO GO FIRST, JULIE.

8925
05:36:25,034 --> 05:36:26,269
ZAZA, YOU'RE NOT GOING TO SAY

8926
05:36:26,269 --> 05:36:26,603
ANYTHING?

8927
05:36:26,603 --> 05:36:32,542
NO, NO, EDWARD IS FIRST.

8928
05:36:32,542 --> 05:36:34,611
>> FIRST I WOULD LIKE TO
SAY

8929
05:36:34,611 --> 05:36:35,445
THANK YOU TO THE AMERICAN

8930
05:36:35,445 --> 05:36:37,714
PEOPLE.

8931
05:36:37,714 --> 05:36:40,950
YOUR GENEROSITY HAS SAVED

8932
05:36:40,950 --> 05:36:42,252
MILLIONS OF LIVES OVER THE LAST

8933
05:36:42,252 --> 05:36:46,222
20 YEARS.

8934
05:36:46,222 --> 05:36:51,561
AND TWO, THE NIH AND THE OTHER

8935
05:36:51,561 --> 05:36:52,629
INSTITUTIONS THAT HAVE PROVIDED

8936
05:36:52,629 --> 05:36:54,397
TRAINING FOR PEOPLE FROM LOW AND

8937
05:36:54,397 --> 05:36:55,765
MIDDLE INCOME COUNTRIES ACROSS

8938
05:36:55,765 --> 05:36:59,769
THE SPECTRUM, THANK YOU.

8939
05:36:59,769 --> 05:37:02,805
AND NOW TH THE INCREASING

8940
05:37:02,805 --> 05:37:04,340
COMMITMENT THAT WE ARE SEEING

8941
05:37:04,340 --> 05:37:07,043
TARGETING SUPPORTING RESEARCHERS

8942
05:37:07,043 --> 05:37:08,378
AND COMMUNITY PEOPLE AND

8943
05:37:08,378 --> 05:37:11,347
ADVOCATES TO DO THIS WORK IN

8944
05:37:11,347 --> 05:37:12,315
AFRICA IS MOVING IN THE RIGHT

8945
05:37:12,315 --> 05:37:14,551
DIRECTION.

8946
05:37:14,551 --> 05:37:18,121
SO SO FAR, YOU'VE GIVEN US --

8947
05:37:18,121 --> 05:37:19,722
YOU'VE TAUGHT US HOW TO FISH,

8948
05:37:19,722 --> 05:37:21,090
AND YOU'RE BEGINNING TO GIVE US

8949
05:37:21,090 --> 05:37:23,860
SOME FISHING HOOKS.

8950
05:37:23,860 --> 05:37:25,995
THE NEXT THING I THINK WE WANT

8951
05:37:25,995 --> 05:37:29,465
TO SEE IS INCREASING -- IS YOU

8952
05:37:29,465 --> 05:37:31,100
TEACHING US ACTUALLY HOW TO MAKE

8953
05:37:31,100 --> 05:37:33,670
THE FISHING HOOKS OURSELVES SO

8954
05:37:33,670 --> 05:37:35,939
THAT WHEN THAT TIME COMES, WE

8955
05:37:35,939 --> 05:37:37,674
CAN HELP OURSELVES MUCH BETTER.

8956
05:37:37,674 --> 05:37:39,175
THANK YOU.

8957
05:37:39,175 --> 05:37:45,481
[APPLAUSE]

8958
05:37:45,481 --> 05:37:47,116
>> MAYBE JUST ONE POINT
THAT WE

8959
05:37:47,116 --> 05:37:49,085
DIDN'T JUST POINT OUT BECAUSE

8960
05:37:49,085 --> 05:37:51,721
THE PROBLEM IS MULTI-LAYERED, SO

8961
05:37:51,721 --> 05:37:52,956
THERE'S THE ISSUE OF ALSO

8962
05:37:52,956 --> 05:37:54,457
ATTRACTING YOUNG TALENT, LIKE

8963
05:37:54,457 --> 05:37:56,192
EDWARD HERE.

8964
05:37:56,192 --> 05:37:58,061
SO I'VE BEEN WORKING IN SOUTH

8965
05:37:58,061 --> 05:37:59,762
AFRICA FOR MORE THAN 10 YEARS

8966
05:37:59,762 --> 05:38:02,298
NOW, AND THE KEY TO, YOU KNOW,

8967
05:38:02,298 --> 05:38:04,701
THE SUCCESSFUL PROGRAM IS

8968
05:38:04,701 --> 05:38:06,869
ATTRACTING YOUNG TALENT, AND SO

8969
05:38:06,869 --> 05:38:08,171
TO ATTRACT AND RETAINING THE

8970
05:38:08,171 --> 05:38:08,605
TALENT.

8971
05:38:08,605 --> 05:38:11,274
SO WE'VE DONE VERY WELL TO

8972
05:38:11,274 --> 05:38:12,508
ATTRACT, YOU'VE DONE VERY WELL

8973
05:38:12,508 --> 05:38:15,011
TO TRAIN, BUT YOU'VE DONE VERY

8974
05:38:15,011 --> 05:38:18,381
POORLY AT RETAINING.

8975
05:38:18,381 --> 05:38:21,317
MORE THAN 90% OF PEOPLE WITH

8976
05:38:21,317 --> 05:38:22,185
PH.D.s I'VE TRAINED MYSELF

8977
05:38:22,185 --> 05:38:23,386
HAVE LEFT THE CONTINENT, AND

8978
05:38:23,386 --> 05:38:24,621
THAT IS A PROBLEM, AND I DON'T

8979
05:38:24,621 --> 05:38:26,089
KNOW WHAT THE SOLUTION IS TO

8980
05:38:26,089 --> 05:38:28,758
THAT, BUT AS LONG AS WE KEEP

8981
05:38:28,758 --> 05:38:32,695
LOSING GOOD TALENT TO THE WEST,

8982
05:38:32,695 --> 05:38:34,197
THEY COME FOR VISITING THE LAB

8983
05:38:34,197 --> 05:38:38,501
AND END UP STAYING.

8984
05:38:38,501 --> 05:38:39,302
IT'S ALWAYS GOING TO BE

8985
05:38:39,302 --> 05:38:40,970
DIFFICULT AND THAT'S SOMETHING

8986
05:38:40,970 --> 05:38:41,871
THAT ALSO NEEDS TO BE THOUGHT

8987
05:38:41,871 --> 05:38:44,874
ABOUT IN TERMS OF CAREER

8988
05:38:44,874 --> 05:38:46,075
PROGRESSION, AND WHEN PEOPLE AT

8989
05:38:46,075 --> 05:38:48,544
THE END OF THEIR TRAINING, THEY

8990
05:38:48,544 --> 05:38:49,779
COME TO YOU AND SAY WHAT NEXT,

8991
05:38:49,779 --> 05:38:51,014
YOU DON'T HAVE AN ANSWER,

8992
05:38:51,014 --> 05:38:52,982
THERE'S NO FACULTY POSITION,

8993
05:38:52,982 --> 05:38:55,351
THERE ARE NO -- THE LIMITED

8994
05:38:55,351 --> 05:38:57,053
OPPORTUNITIES FOR PEOPLE IN

8995
05:38:57,053 --> 05:38:58,921
SCIENCE TO HAVE A CAREER ON THE

8996
05:38:58,921 --> 05:39:01,024
CONTINENT AND TO PROGRESS.

8997
05:39:01,024 --> 05:39:03,793
THERE ARE VERY FEW PEOPLE LIKE

8998
05:39:03,793 --> 05:39:05,762
ME WHO CAME AND GOT A GOOD

8999
05:39:05,762 --> 05:39:07,030
EDUCATION IN THE U.S. AND WENT

9000
05:39:07,030 --> 05:39:08,364
BACK AND MADE A MEANINGFUL

9001
05:39:08,364 --> 05:39:09,365
CAREER OUT OF IT.

9002
05:39:09,365 --> 05:39:11,734
IT'S NOT BEEN EASY BUT IT'S VERY

9003
05:39:11,734 --> 05:39:12,368
RARE.

9004
05:39:12,368 --> 05:39:15,038
THERE ARE FEW PEOPLE THAT HAVE

9005
05:39:15,038 --> 05:39:17,407
DONE THAT, BUT MOST PEOPLE FAIL

9006
05:39:17,407 --> 05:39:19,375
TO DO THAT AND ESPECIALLY

9007
05:39:19,375 --> 05:39:20,476
OUTSIDE SOUTH AFRICA, IT'S

9008
05:39:20,476 --> 05:39:21,444
EXTREMELY DIFFICULT, SO IT'S THE

9009
05:39:21,444 --> 05:39:23,446
IDEA OF CAPACITY BUILDING AS

9010
05:39:23,446 --> 05:39:25,314
HAPPENED QUITE A BIT ABOUT

9011
05:39:25,314 --> 05:39:27,750
TRAINING PEOPLE BUT THE

9012
05:39:27,750 --> 05:39:30,053
RETENTION AND PATHWAY TO BEING

9013
05:39:30,053 --> 05:39:31,220
INDEPENDENT INVESTIGATOR ON THE

9014
05:39:31,220 --> 05:39:32,422
CONTINENT IS NOT VERY

9015
05:39:32,422 --> 05:39:32,989
WELL-DEFINED AT THE MOMENT.

9016
05:39:32,989 --> 05:39:37,293
THANK YOU.

9017
05:39:37,293 --> 05:39:39,462
>> THANK YOU, EVERYONE,
WHO HAS

9018
05:39:39,462 --> 05:39:40,763
STAYED AROUND TO THE END.

9019
05:39:40,763 --> 05:39:41,798
APPRECIATE YOUR TIME.

9020
05:39:41,798 --> 05:39:44,600
I JUST HAD JUST A FEW COMMENTS.

9021
05:39:44,600 --> 05:39:47,904
I WAS JUST LOOKING AT THE

9022
05:39:47,904 --> 05:39:49,205
NOSIs THAT HAVE COME OUT AND I

9023
05:39:49,205 --> 05:39:50,206
SEE THERE'S SO MUCH OPPORTUNITY

9024
05:39:50,206 --> 05:39:50,540
IN THERE.

9025
05:39:50,540 --> 05:39:52,141
THERE'S SO MUCH THAT CAN BE

9026
05:39:52,141 --> 05:39:53,810
DONE, THERE'S SO MUCH THAT --

9027
05:39:53,810 --> 05:39:55,144
AND WHEN YOU LOOK AT ALL THESE,

9028
05:39:55,144 --> 05:39:59,182
THERE'S SO MUCH, MYSELF, I'M

9029
05:39:59,182 --> 05:40:00,850
LIKE OKAY, ME AND MY GROUP ARE

9030
05:40:00,850 --> 05:40:02,585
PLANNING TO PUT IN MAYBE LIKE

9031
05:40:02,585 --> 05:40:04,821
TWO OF THEM, BUT I'M LIKE OKAY,

9032
05:40:04,821 --> 05:40:07,156
SO WE PUT IN, DO WE STAND A

9033
05:40:07,156 --> 05:40:07,690
CHANCE?

9034
05:40:07,690 --> 05:40:10,093
MOST TIMES, IS IT LIKELY THAT

9035
05:40:10,093 --> 05:40:12,261
THE ONES -- THE PLAYERS ARE THE

9036
05:40:12,261 --> 05:40:13,529
ONES WHO ARE GOING TO GET THEM

9037
05:40:13,529 --> 05:40:16,099
OR IS THERE AN OPPORTUNITY THAT

9038
05:40:16,099 --> 05:40:17,934
NEW KIDS ON THE BLOCK ARE

9039
05:40:17,934 --> 05:40:19,001
GETTING THESE OPPORTUNITIES,

9040
05:40:19,001 --> 05:40:22,171
BECAUSE IT'S REALLY SO DIVERSE,

9041
05:40:22,171 --> 05:40:23,139
BUT IF OPPORTUNITIES ARE OPEN

9042
05:40:23,139 --> 05:40:24,974
NOT TO EVERYONE BUT WHO IS ABLE,

9043
05:40:24,974 --> 05:40:27,477
I THINK THERE IS MUCH FOR

9044
05:40:27,477 --> 05:40:27,977
EVERYONE.

9045
05:40:27,977 --> 05:40:30,513
AND I'M ALSO LOOKING AT AN

9046
05:40:30,513 --> 05:40:31,414
OPPORTUNITY LIKE IS THERE A

9047
05:40:31,414 --> 05:40:34,050
CHANCE OF HAVING AFRICAN GRANTS

9048
05:40:34,050 --> 05:40:34,917
FOR AFRICANS?

9049
05:40:34,917 --> 05:40:38,821
BECAUSE NOW THIS IS LMICs BUT

9050
05:40:38,821 --> 05:40:41,924
YES, CAN WE HAVE THE OPPORTUNITY

9051
05:40:41,924 --> 05:40:43,326
TO PUT IN AND CONSIDERED SO AS

9052
05:40:43,326 --> 05:40:44,961
WE GET THIS, WE ARE BUILDING

9053
05:40:44,961 --> 05:40:45,228
CAPACITY.

9054
05:40:45,228 --> 05:40:47,764
WHEN YOU GET A GRANT, IT REALLY

9055
05:40:47,764 --> 05:40:49,532
BRINGS -- IT JUST TAKES YOU

9056
05:40:49,532 --> 05:40:52,869
FORTH INTO SOMETHING ELSE AND

9057
05:40:52,869 --> 05:40:54,270
MORE AND TO MORE AND TO MORE.

9058
05:40:54,270 --> 05:40:56,873
ALSO THE OTHER THING WOULD MAYBE

9059
05:40:56,873 --> 05:40:58,474
BE AS THESE GRANTS ARE BEING

9060
05:40:58,474 --> 05:41:01,811
AWARDED, IS THERE AN OPPORTUNITY

9061
05:41:01,811 --> 05:41:04,347
OF EXPLAINING THE DEVELOPMENTAL

9062
05:41:04,347 --> 05:41:05,548
AWARDS, THESE ARE SMALL GRANTS

9063
05:41:05,548 --> 05:41:08,084
THAT CAN HELP NEWER PEOPLE COME

9064
05:41:08,084 --> 05:41:11,387
ON BOARD AND THEN EXPAND THEIR

9065
05:41:11,387 --> 05:41:12,755
EXPERTISE.

9066
05:41:12,755 --> 05:41:14,123
SO IF YOU HAVE MORE

9067
05:41:14,123 --> 05:41:14,724
DEVELOPMENTAL GRANTS, THEN

9068
05:41:14,724 --> 05:41:15,725
YOU'LL HAVE MORE PEOPLE HAVING

9069
05:41:15,725 --> 05:41:18,528
MORE OPPORTUNITIES TO WRITE EVEN

9070
05:41:18,528 --> 05:41:21,164
BIGGER GRANTS, AND THIS WILL

9071
05:41:21,164 --> 05:41:22,064
EXPAND THE EXPERTISE ON

9072
05:41:22,064 --> 05:41:22,331
CONTINENT.

9073
05:41:22,331 --> 05:41:26,035
THANK YOU.

9074
05:41:26,035 --> 05:41:28,571
>> ANY OTHER COMMENTS?

9075
05:41:28,571 --> 05:41:30,139
JULIE, HANEEFA?

9076
05:41:30,139 --> 05:41:31,874
>> I DID ORIGINALLY BUT MY

9077
05:41:31,874 --> 05:41:34,544
COLLEAGUES SAID SO MANY

9078
05:41:34,544 --> 05:41:35,244
IMPORTANT THINGS.

9079
05:41:35,244 --> 05:41:36,979
MAYBE I WOULD JUST COMMENT THAT

9080
05:41:36,979 --> 05:41:42,185
A REALLY KEY IMPORTANT AUDIENCE

9081
05:41:42,185 --> 05:41:43,486
ARE NOT OUR COLLEAGUES IN

9082
05:41:43,486 --> 05:41:45,655
MINISTRIES OF HEALTH BUT ALSO IN

9083
05:41:45,655 --> 05:41:48,124
THE MINISTRIES OF FINANCE.

9084
05:41:48,124 --> 05:41:50,526
IT IS PEOPLE LIKE THAT WHO

9085
05:41:50,526 --> 05:41:52,061
UNDERSTAND THAT VERY WELL AND SO

9086
05:41:52,061 --> 05:41:54,630
I THINK THAT IS A REALLY

9087
05:41:54,630 --> 05:41:55,498
IMPORTANT PIECE OF ADVICE THAT

9088
05:41:55,498 --> 05:41:57,867
WE JUST HEARD FROM, FROM SHARON.

9089
05:41:57,867 --> 05:41:59,135
AND MAYBE THE LAST THING I WOULD

9090
05:41:59,135 --> 05:42:01,137
SAY IS THAT WE ARE SO INDEBTED

9091
05:42:01,137 --> 05:42:04,874
TO THE VOLUNTEERS THAT HAVE --

9092
05:42:04,874 --> 05:42:06,275
AND PARTICIPANTS IN STUDIES WHO

9093
05:42:06,275 --> 05:42:10,413
HAVE TAKEN US SO FAR IN THE

9094
05:42:10,413 --> 05:42:11,514
EARLY PHASE, MAYBE THE END OF

9095
05:42:11,514 --> 05:42:13,249
THE BEGINNING, RIGHT, OF HIV

9096
05:42:13,249 --> 05:42:18,821
CURE RESEARCH, PRIMARILY HERE

9097
05:42:18,821 --> 05:42:19,322
BASED IN THE U.S.

9098
05:42:19,322 --> 05:42:24,227
FOR EVERY ONE OF THROWS VALU THD

9099
05:42:24,227 --> 05:42:24,794
PARTICIPANTS, THERE ARE

9100
05:42:24,794 --> 05:42:27,830
THOUSANDS OF PEOPLE GLOBALLY

9101
05:42:27,830 --> 05:42:29,332
WHOSE VOICE MAY NOT BE HEARD

9102
05:42:29,332 --> 05:42:30,867
BECAUSE OF THEIR PERSONAL

9103
05:42:30,867 --> 05:42:31,734
CIRCUMSTANCES OR JUST THE

9104
05:42:31,734 --> 05:42:33,169
SETTING IN WHICH THAT THEY LIVE.

9105
05:42:33,169 --> 05:42:35,605
THESE INITIATIVES, THESE FOCUSED

9106
05:42:35,605 --> 05:42:38,341
COORDINATED EFFORTS TO REALLY

9107
05:42:38,341 --> 05:42:39,642
ELEVATE NOT JUST CLINICAL, I

9108
05:42:39,642 --> 05:42:43,379
SHOULD SAY ALSO THE KEY

9109
05:42:43,379 --> 05:42:45,147
IMPORTANCE OF THE OUTCOME BASIC

9110
05:42:45,147 --> 05:42:46,616
RESEARCH BEING DONE IN LOW AND

9111
05:42:46,616 --> 05:42:48,684
MIDDLE INCOME SETTINGS, THIS IS

9112
05:42:48,684 --> 05:42:50,052
REALLY ELEVATING RAISING THOSE

9113
05:42:50,052 --> 05:42:50,386
VOICES.

9114
05:42:50,386 --> 05:42:52,922
I MEAN, INCREDIBLY IMPACTFUL,

9115
05:42:52,922 --> 05:42:53,890
SOME OF THE MOST IMPORTANT WORK

9116
05:42:53,890 --> 05:42:55,758
WE CAN POSSIBLY BE DOING AS A

9117
05:42:55,758 --> 05:42:56,592
COMMUNITY, EVERYONE IN THIS

9118
05:42:56,592 --> 05:42:57,927
ROOM, IT'S JUST REALLY

9119
05:42:57,927 --> 05:43:00,229
FULFILLING TO BE HAVING THIS

9120
05:43:00,229 --> 05:43:04,467
DISCUSSION AT THIS TIME.

9121
05:43:04,467 --> 05:43:07,403
>> OKAY, LAST WORDS DOWN
THERE

9122
05:43:07,403 --> 05:43:15,111
AT THE END OF THE PANEL HERE.

9123
05:43:15,111 --> 05:43:17,213
>> I JUST WANT TO BE
QUICK.

9124
05:43:17,213 --> 05:43:19,181
JUST SORT OF REITERATE THAT WE

9125
05:43:19,181 --> 05:43:20,816
DO HAVE THE CFAR AFRICA PROGRAM.

9126
05:43:20,816 --> 05:43:22,652
IT'S NOT GOING TO ADDRESS ALL OF

9127
05:43:22,652 --> 05:43:25,054
THE PROBLEMS AND ALL OF THE

9128
05:43:25,054 --> 05:43:27,757
CHALLENGES, BUT IT IS ONE STEP

9129
05:43:27,757 --> 05:43:29,992
TO REALLY INVEST IN NEW

9130
05:43:29,992 --> 05:43:32,028
INVESTIGATORS, EARLY CAREER

9131
05:43:32,028 --> 05:43:34,163
INVESTIGATORS, AND IT REALLY

9132
05:43:34,163 --> 05:43:35,197
TARGETING INVESTIGATORS WHO ARE

9133
05:43:35,197 --> 05:43:36,866
BASED IN AFRICA WHO HAVE

9134
05:43:36,866 --> 05:43:38,634
AFFILIATIONS IN AFRICAN

9135
05:43:38,634 --> 05:43:40,569
INSTITUTIONS TO TRY TO AVOID

9136
05:43:40,569 --> 05:43:44,607
SOME OF THAT BRAIN DRAIN OR AT

9137
05:43:44,607 --> 05:43:46,676
LEAST TRY TO MITIGATE SOME OF

9138
05:43:46,676 --> 05:43:47,343
THAT BRAIN DRAIN.

9139
05:43:47,343 --> 05:43:49,011
SO WE'RE REALLY EXCITED TO GET

9140
05:43:49,011 --> 05:43:52,548
STARTED ON THIS INITIATIVE, AND

9141
05:43:52,548 --> 05:43:54,684
REALLY FOCUS ON INVESTING IN

9142
05:43:54,684 --> 05:43:57,820
THOSE EARLY STAGE INVESTIGATORS.

9143
05:43:57,820 --> 05:43:59,322
>> I'LL ALSO BE BRIEF.

9144
05:43:59,322 --> 05:44:01,157
I THINK WE TALKED A LOT ABOUT

9145
05:44:01,157 --> 05:44:02,692
THE FUNDING OPPORTUNITIES.

9146
05:44:02,692 --> 05:44:04,560
I THINK I'M ALSO LOOKING AT

9147
05:44:04,560 --> 05:44:06,162
SPECIFICITY OF AS WE'RE TALKING

9148
05:44:06,162 --> 05:44:08,864
ABOUT THE HIV CURE RESEARCH

9149
05:44:08,864 --> 05:44:12,201
FUNDING WE SHOULD ALSO THINK OF

9150
05:44:12,201 --> 05:44:12,835
COMMUNITY-SPECIFIC, I KNOW WE

9151
05:44:12,835 --> 05:44:14,437
ONLY TALK ABOUT -- WE ONLY TALK

9152
05:44:14,437 --> 05:44:18,641
SO MUCH ABOUT COMMUNITY

9153
05:44:18,641 --> 05:44:19,608
ENROLLMENT, FOLLOW UP SHOULD

9154
05:44:19,608 --> 05:44:21,510
ALSO BE SPECIFIC AND STANDALONE

9155
05:44:21,510 --> 05:44:22,645
COMMUNITY RESOURCES.

9156
05:44:22,645 --> 05:44:24,280
AND I'M ALSO THINKING THERE ARE

9157
05:44:24,280 --> 05:44:25,514
MANY GLOBAL COMMITMENTS THAT

9158
05:44:25,514 --> 05:44:27,083
GOVERNMENT AND HEAD OF STATES

9159
05:44:27,083 --> 05:44:27,616
MAKE.

9160
05:44:27,616 --> 05:44:28,918
I THINK IT'S ALSO ABOUT TIME WE

9161
05:44:28,918 --> 05:44:30,786
START MAKING COMMITMENTS TOWARDS

9162
05:44:30,786 --> 05:44:32,555
HIV CURE RESEARCH AS WELL AS --

9163
05:44:32,555 --> 05:44:33,122
AND RESOURCES.

9164
05:44:33,122 --> 05:44:34,390
I THINK THIS IS SOMETHING THAT

9165
05:44:34,390 --> 05:44:37,126
WE CAN EASILY FOLLOW UP IF IT'S

9166
05:44:37,126 --> 05:44:37,626
DOCUMENTED AS WELL.

9167
05:44:37,626 --> 05:44:41,364
THANK YOU.

9168
05:44:41,364 --> 05:44:43,699
>> THANK YOU TO THE WHOLE
PANEL.

9169
05:44:43,699 --> 05:44:49,205
[APPLAUSE]

9170
05:44:49,205 --> 05:44:52,408
I TURN IT OVER TO OUR

9171
05:44:52,408 --> 05:45:01,851
COLLEAGUES, KARL.

9172
05:45:01,851 --> 05:45:03,786
>> THANKS A LOT.

9173
05:45:03,786 --> 05:45:07,156
APPRECIATE IT.

9174
05:45:07,156 --> 05:45:08,724
SO JUST A FEW CLOSING REMARKS

9175
05:45:08,724 --> 05:45:10,860
BEFORE I HAND IT OVER TO KARL.

9176
05:45:10,860 --> 05:45:15,765
SO WE HAD TWO DAYS OF FA FANTASC

9177
05:45:15,765 --> 05:45:16,198
SCIENTIFIC TREAT.

9178
05:45:16,198 --> 05:45:17,133
THIS WOULD NOT HAVE BEEN

9179
05:45:17,133 --> 05:45:18,567
POSSIBLE WITHOUT THE SUPPORT OF

9180
05:45:18,567 --> 05:45:19,101
OUR LEADERSHIP.

9181
05:45:19,101 --> 05:45:22,571
I WANT TO THANK THE DIRECTOR OF

9182
05:45:22,571 --> 05:45:23,672
NIAID, ESPECIALLY FOR AGREEING

9183
05:45:23,672 --> 05:45:26,142
TO GIVE OPENING REMARKS, AND

9184
05:45:26,142 --> 05:45:28,677
KARL DIEFFENBACH, DIRECTOR OF

9185
05:45:28,677 --> 05:45:32,581
THE DIVISION OF AIDS FOR SUPPORT

9186
05:45:32,581 --> 05:45:33,716
OF THE CURE PROGRAM AND DIRECTOR

9187
05:45:33,716 --> 05:45:37,386
OF BASIC SCIENCE PROGRAM,

9188
05:45:37,386 --> 05:45:39,388
DR. DIANA FINZI FOR GUIDING US

9189
05:45:39,388 --> 05:45:43,359
THROUGH THIS PROCESS, AND OF

9190
05:45:43,359 --> 05:45:44,894
COURSE KARL FOR TRUSTING US TO

9191
05:45:44,894 --> 05:45:46,062
RUN THIS PROGRAM AND THIS

9192
05:45:46,062 --> 05:45:47,063
MEETING THIS WOULD NOT HAVE BEEN

9193
05:45:47,063 --> 05:45:48,297
POSSIBLE WITHOUT THE PROGRAM

9194
05:45:48,297 --> 05:45:49,598
MANAGEMENT TEAM WHICH CONSISTS

9195
05:45:49,598 --> 05:45:51,333
OF PROGRAM OFFICERS FROM OTHER

9196
05:45:51,333 --> 05:45:52,735
ICs, BUT I'M ESPECIALLY

9197
05:45:52,735 --> 05:45:55,171
THANKFUL TO MY COLLEAGUES IN MY

9198
05:45:55,171 --> 05:45:56,472
BRANCH, PATHOGENESIS AND

9199
05:45:56,472 --> 05:45:57,406
THERAPEUTICS INTERVENTIONS

9200
05:45:57,406 --> 05:45:58,974
BRANCH, WITHOUT THEIR HELP, IT'S

9201
05:45:58,974 --> 05:46:01,110
A TEAM EFFORT, SO I'M GLAD I

9202
05:46:01,110 --> 05:46:02,745
WOULD CALL THIS AS A GREAT

9203
05:46:02,745 --> 05:46:02,978
SUCCESS.

9204
05:46:02,978 --> 05:46:05,714
AND I JUST WANT TO THANK THE

9205
05:46:05,714 --> 05:46:06,816
CO-SPONSORS ICs WHO HAVE

9206
05:46:06,816 --> 05:46:08,751
SUPPORTED THIS PROGRAM.

9207
05:46:08,751 --> 05:46:09,919
AND ESPECIALLY THE MEMBERS OF

9208
05:46:09,919 --> 05:46:10,953
THE COLLABORATORY.

9209
05:46:10,953 --> 05:46:12,288
WITHOUT THEIR SCIENTIFIC

9210
05:46:12,288 --> 05:46:13,089
PRESENTATION, THIS WOULD NOT

9211
05:46:13,089 --> 05:46:14,190
HAVE BEEN COMPLETE.

9212
05:46:14,190 --> 05:46:15,858
I THANK EVERY ONE OF THEM WHO

9213
05:46:15,858 --> 05:46:16,992
CAME HERE ALL THE WAY TO MAKE

9214
05:46:16,992 --> 05:46:18,027
THIS A GREAT EVENT.

9215
05:46:18,027 --> 05:46:21,230
SO WE ARE ABOUT 503 REGISTRANTS

9216
05:46:21,230 --> 05:46:23,065
AND 30 ON SITE, AND THERE WERE

9217
05:46:23,065 --> 05:46:24,900
ABOUT 350 PEOPLE WATCHING IT

9218
05:46:24,900 --> 05:46:26,569
VIRTUALLY ON NIH VIDEOCAST.

9219
05:46:26,569 --> 05:46:27,670
WE THANK THEM ALL.

9220
05:46:27,670 --> 05:46:31,807
AND FINALLY, I WANT TO THANK THE

9221
05:46:31,807 --> 05:46:32,241
SPONSORS.

9222
05:46:32,241 --> 05:46:33,943
WE DID NOT KNOW WHETHER WE WOULD

9223
05:46:33,943 --> 05:46:36,178
HAVE THE CA CAFETERIA OPEN IN TE

9224
05:46:36,178 --> 05:46:37,580
LAST TWO DAYS BUT WE DID, WE

9225
05:46:37,580 --> 05:46:38,948
WERE PERSISTENT, WE MADE THEM

9226
05:46:38,948 --> 05:46:40,916
OPEN AT LEAST FOR THESE TWO DAYS

9227
05:46:40,916 --> 05:46:42,651
AND FOR THE COFFEE SERVICE THAT

9228
05:46:42,651 --> 05:46:45,154
WE HAD FREE PROVIDED BY THE

9229
05:46:45,154 --> 05:46:46,922
FAES, AND I WANT TO THANK THE

9230
05:46:46,922 --> 05:46:48,991
NIH EVENTS STAFF FOR FANTASTIC

9231
05:46:48,991 --> 05:46:50,192
SUPPORT, THE CONFERENCE PEOPLE,

9232
05:46:50,192 --> 05:46:51,160
THE GUY IN THE BOOTH, THANK YOU,

9233
05:46:51,160 --> 05:46:53,729
AND MILES HERE.

9234
05:46:53,729 --> 05:46:54,330
FANTASTIC.

9235
05:46:54,330 --> 05:46:56,899
IT'S BEEN WONDERFUL SUPPORT,

9236
05:46:56,899 --> 05:46:57,900
REALLY APPRECIATE THE NIH VIDEO

9237
05:46:57,900 --> 05:46:58,234
STAFF.

9238
05:46:58,234 --> 05:46:59,668
THEY'VE BEEN TELECASTING THIS,

9239
05:46:59,668 --> 05:47:01,403
AND I GET WONDERFUL RESPONSE

9240
05:47:01,403 --> 05:47:03,038
FROM THEM, FROM THE PEOPLE

9241
05:47:03,038 --> 05:47:03,806
WATCHING WORLDWIDE.

9242
05:47:03,806 --> 05:47:04,340
IT'S WONDERFUL.

9243
05:47:04,340 --> 05:47:07,042
AND I WANT TO THANK THE NIAID

9244
05:47:07,042 --> 05:47:08,177
EVENTS PEOPLE WHO ARE

9245
05:47:08,177 --> 05:47:09,345
RESPONSIBLE FOR CREATING THE

9246
05:47:09,345 --> 05:47:10,446
WEBSITE.

9247
05:47:10,446 --> 05:47:15,684
AND THE CONFERENCE SERVICES,

9248
05:47:15,684 --> 05:47:17,286
LUMINA, THOSE ARE THE LADIES WHO

9249
05:47:17,286 --> 05:47:18,487
WERE AT THE REGISTRATION DESK,

9250
05:47:18,487 --> 05:47:21,557
THEY DID A PHENOMENAL JOB,

9251
05:47:21,557 --> 05:47:22,124
FANTASTIC SUPPORT SERVICE.

9252
05:47:22,124 --> 05:47:23,459
WITH THAT I WANT TO HAND IT OVER

9253
05:47:23,459 --> 05:47:23,993
TO KARL.

9254
05:47:23,993 --> 05:47:24,527
THANK YOU ALL.

9255
05:47:24,527 --> 05:47:27,763
[APPLAUSE]

9256
05:47:27,763 --> 05:47:32,234
>> I JUST WANT TO THANK
UDAI FOR

9257
05:47:32,234 --> 05:47:33,002
LEADING THE ORGANIZATION OF THE

9258
05:47:33,002 --> 05:47:35,538
MEETING THIS YEAR, DID A

9259
05:47:35,538 --> 05:47:37,740
FANTASTIC JOB ALONG WITH HIS

9260
05:47:37,740 --> 05:47:38,474
COLLEAGUES, AS WELL AS ALL THE

9261
05:47:38,474 --> 05:47:41,177
OTHER PROGRAM STAFF.

9262
05:47:41,177 --> 05:47:44,313
SO THANKS, UDAI, FOR DOING A

9263
05:47:44,313 --> 05:47:46,182
GREAT JOB.

9264
05:47:46,182 --> 05:47:48,083
WE DON'T HAVE A DATE YET FOR THE

9265
05:47:48,083 --> 05:47:49,285
NEXT ITERATION OF THE STRATEGIES

9266
05:47:49,285 --> 05:47:52,254
FOR A CURE IN 2025 PRESUMABLY,

9267
05:47:52,254 --> 05:47:54,690
BUT WE'LL BE SENDING OUT SOME

9268
05:47:54,690 --> 05:47:56,659
SURVEYS AND WE WELCOME ALL

9269
05:47:56,659 --> 05:47:58,060
FEEDBACK ON HOW WE CAN MAKE THIS

9270
05:47:58,060 --> 05:48:00,062
MEETING BETTER AS WELL AS WHAT

9271
05:48:00,062 --> 05:48:01,564
THE NEXT JOINT MDC MEETING

9272
05:48:01,564 --> 05:48:03,632
SHOULD BE FOR NEXT YEAR.

9273
05:48:03,632 --> 05:48:05,067
SO SAFE TRAVELS, EVERYONE, AND

9274
05:48:05,067 --> 05:48:06,268
THANK YOU FOR YOUR

9275
05:48:06,268 --> 05:48:06,602
PARTICIPATION.

9276
05:48:06,602 --> 05:48:16,779
[APPLAUSE]