>>WELCOME TO
THE JANUARY 2022 AIDS UNIVERSITY
COUNCIL I'M KEN FREEDBERG AND
THIS IS A MEETING PLANNED TO BE
VIRTUAL FOR A WHILE FOR THOSE OF
US IN BOSTON WITH 24 INCHES OF
SNOW ON SATURDAY NOT REGRETTING
NOT TRYING TO GET TO NIH TODAY.
AND I KNOW THAT HOPEFULLY IN
SEPTEMBER WE'LL SEE EACH OTHER
IN PERSON AND THERE'LL BE
NEITHER SNOW NOR REASON WE CAN'T
GET TOGETHER.
WELCOME EVERYONE.
THE FIRST ORDER OF BUSINESS IS
TO APPROVE THE MINUTES OF THE
LAST MEETING CIRCULATED SEVERAL
WEEKS AGO.
I HOPE PEOPLE HAVE HAD A CHANCE
TO REVIEW THOSE AND WONDERING IF
I CAN HAVE A MOTION TO ACCEPT
THE MINUTES.
>> SO MOVED.
>> CAN SOMEONE SECOND THE
MOTION?
WE HAVE A MOTION TO ACCEPT THE
MINUTES OF OUR SEPTEMBER MEETING
AND ANY DEBATE ON THAT QUESTION?
COULD WE HAVE A VOTE ON THAT TO
APPROVE THE MINUTES?
ANYONE IN FAVOR?
>> AYE.
>> ANYONE OPPOSED?
OKAY.
WE HAVE A UNANIMOUS VOTE TO
APPROVE THE MINUTES OF OUR
PREVIOUS MEETING, THANK YOU
EVERYONE.
AND PAM FOR PUTTING THE MINUTES
TOGETHER.
SO OUR FIRST TALK WILL BE THE
DIRECTOR'S REPORT FROM CARL
DIEFFENBACH AND WE LOOK FORWARD
TO HEARING FROM YOU.
>> THANK YOU, KEN.
IT'S A PLEASURE TO BE JOINING
YOU TODAY.
WE HAD A DUSTING OF SNOW IN
WASHINGTON BUT IT'S STILL REALLY
COLD.
HERE'S AN OUTLINE FOR THE RUN OF
SHOW TODAY.
I'LL PROVIDE THE DIRECTOR'S
REPORT INCLUDING THE SPIR
CONTRACT TOPIC AND TRISH BURDO
WILL PROVIDE AN UPDATE AND THEN
WE'LL HAVE THE USUAL
PROGRAMMATIC INTERVIEWS TO SET
THE STAGE FOR THE RESEARCH
INITIATIVES WE ARE HAVING IN THE
WORK AND PLANNING FOR THE
FUTURE.
IT'S A WAY OF KEEPING THE SENSE
OF DIRECTION FROM THE DIVISION
IN YOUR MIND'S EYE AS WE MOVE
FORWARD AND WE DO THIS EVERY
JANUARY.
IT'S A REAL PLEASURE TO WELCOME
KEITH JEROME AS A MEMBER OF THE
ADVISORY COUNCIL HE'S A
PHYSICIAN AND VIROLOGIST IN THE
INFECTIOUS DISEASE DIVISION AND
PROFESSOR IN THE DEPARTMENT OF
LABORATORY MEDICINE AND
PATHOLOGY AS WELL AS HEAD OF
VIROLOGY DIVISION AT THE
UNIVERSITY OF WASHINGTON.
KEITH'S FOCUS OF HIS RESEARCH IS
THE BIOLOGY OF CHRONIC VIRAL
INFECTIONS AND HE WORKS ON
SEVERAL INCLUDING ATTEMPT TO
CURE HIV, HEPATITIS B AND
PAPILLOMA AND HERPES INFECTION.
IN TERMS OF NEW APPOINTMENTS,
IT'S MY PLEASURE TO WELCOME FA
FATIMAH JONES IN THE THERAPEUTIC
RESEARCH PROGRAM.
HE RECEIVED HER Ph.D. FROM YALE
UNIVERSITY AND COMES FROM 25
YEARS OF COMBINED BASIC RESEARCH
AND PROGRAM AND PROJECT
MANAGEMENT EXPERIENCE.
SHE IS EXPERIENCED IN LABORATORY
SPECIALIST WITH EXPERTISE IN
QUALITY MANAGEMENT AND HIV AND
T.B. DIAGNOSTICS AND CLINICAL
LABORATORY OPERATIONS IN THE
INTERNATIONAL AND DOMESTIC
SETTINGS?
MOST RECENTLY SHE WAS THE
PROJECT DIRECTOR WHERE SHE
COLLABORATED WITH SPONSORS AND
MINISTRIES OF HEALTH FOR
LABORATORY STRENGTHENING
INITIATIVES.
WE'VE BEEN WORKING WITH HER FOR
YEARS.
SHE WAS IN THE EARLIER PART OF
HER CAREER THE LEAD PERSON AT
FISCHER BIOSCIENCES WORKING WITH
US ALMOST ON A DAY TO DAY BASIS
WITH THE RE-AGENT PROGRAM AND
YOU KNOW HOW VALUABLE THAT IS TO
THE DIVISION.
SHE DID A STENT WITH THE DRUG
RESISTANT PROGRAM AT FREDERICK.
HER EXPERIENCE IS IDEALLY SUITED
TO BE THE CHIEF OF DDCSB AND
WELCOME.
WE'RE ON A CONTINUOUS RESOLUTION
UNTIL THE BUDGET IS APPROVED AND
THE HOUSE AND SENATE EACH HAVE
THEIR OWN SENSE OF WHAT THEY
WOULD LIKE TO APPROPRIATE AND
THAT NEEDS TO GET WORKED OUT.
THERE'S A SENSE THERE WILL BE A
COVID-19 OR SARS COV2
SUPPLEMENTAL PACKAGE.
THE SIZE AND SCOPE OF THAT
REMAINS TO BE DETERMINED AND
THAT IS ONE OF THE MAJOR
CHALLENGE WE FACE RIGHT NOW
WE'RE IN THIS HOLDING PATTERN
WHERE WE REALLY CAN'T INITIATIVE
A LOT OF NEW THINGS UNDER A C.R.
AND WE CAN'T REALLY GET MOVING
WITH ANYTHING PARTICULARLY NEW
IN CORONAVIRUS 19 RESEARCH UNTIL
THE BUDGET GETS PASSED.
SOMETHING WE DIDN'T SAY LAST
YEAR WHICH HAS BEEN A TRANSITION
SINCE 2008, I LIKE TO GIVE A
REPORT CARD ON WHAT THE DIVISION
HAS DONE OVER TIME IN TERMS OF
ITS PAY LINE AND SUCCESS RATE.
I COULD HAVE IT GO ALL THE WAY
BACK BUT WE TRUNCATED THE LIST
TO THE LAST FIVE YEARS.
THE PERCENTILE HAS GONE UP IN
TERMS OF THE PAY LINE SINCE 2017
WE'VE BEEN HOLDING RELATIVELY
STEADY AT THE 14th AND 18th
PERCENTILES.
IN TERMS OF SUCCESS RATES, THESE
ARE THE NIAID AID SUCCESS RATES
FOR RO1s PROGRAM, PROJECT GRANTS
AND R21s.
SEE IN GENERAL THERE'S
FLUCTUATION BUT IN GENERAL WE'VE
BEEN ABLE TO KEEP THE SUCCESS
RATE IN THE 20s FOR RO1s FOR
R21s AND THE NUMBERS ARE SO
SMALL FOR PO1s, A DROP OF A FEW
APPLICATIONS IN THE SUCCESS RATE
LOOKS LIKE IT'S JUMPED UP QUITE
A BIT BUT SEE THE GENERAL TREND
IS APPROXIMATELY TWO PROGRAM
PROJECTS A YEAR.
BY AND LARGE WE'VE BEEN ABLE TO
MAINTAIN A FAIRLY STEADY
MODESTLY HEALTHY SUCCESS RATE.
AND HOPE TO DO SO IN THE FUTURE.
IT'S IMPORTANT TO CARE THESE --
AGAIN, THIS IS JUST A SUMMARY OF
THE DATA I'VE SHOWED BROKEN OUT
BY FISCAL YEAR.
YOU CAN SEE THE NUMBERS ARE WHAT
THEY ARE.
IMPORTANTLY, THERE WERE MORE
RO1s CAME IN IN FISCAL YEAR '20
THAN A
THAN ANY'
'20.
AND ACROSS THE AIDS BUDGET
WITHIN THE DIVISION OF AIDS, YOU
CAN SEE WE DO FOR '20 AND '21
PARTICULARLY LOOKING AT RPGs AS
A WHOLE.
I'LL STOP THERE AND SEE IF
ANYBODY HAS ANY QUESTIONS ABOUT
THE REPORT CARD BEFORE I MOVE ON
TO SCIENTIFIC AND PROGRAMMATIC
UPDATES.
AUDREY.
>> GREAT, THANKS, CARL.
I FEEL MAYBE WE TALKED ABOUT
THIS LAST YEAR THE GENDER AND
RACE ETHNICITY BACKGROUND, DID
WE DO THAT?
WITH COVID IMPACTS I KNOW
THERE'S BEEN A LOT OF DISCUSSION
ABOUT WOMEN AND BIPOC SCIENTISTS
BEING MORE ADVERSELY AFFECTED
WITH HOME CARE RESPONSIBILITIES
AND LEAVING ACADEMIA AND NOT
WRITING SO IT'S ENCOURAGING THE
PAY RATES HAVEN'T CHANGED I'M
JUST WONDERING IF THERE'S A PLAN
TO DO THAT.
I KNOW WE HAVE TO SIGN OFF ON
SOME OF THE OTHER DIVERSITY
METRICS OF THE REPORT OF THE
INSTITUTE.
>> SO THERE'S A CHALLENGE IN
THAT IN TERMS OF IDENTIFYING
PEOPLE WHO DON'T HOW DO YOU
IDENTIFY PEOPLE WHO DON'T
PARTICIPATE.
I THINK IN GENERAL WE'RE SEEING
A FAIRLY CONSISTENT RESPONSE
ACROSS GENDER.
RACE IS ALSO FAIRLY HARD TO SORT
OUT.
WE'RE COMMITTED TO DIVERSITY AND
INCLUSION AND EQUITY.
IT REMAINS A HIGH PRIORITY FOR
THE DIVISION AND ARE SEEKING
WAYS TO ACHIEVE THAT.
WHAT WE ARE SOMEWHAT -- WE RUN
INTO A PROBLEM SOMETIMES WITH
SOME OF THE IDEAS WE HAVE, GO
COUNTER TO CASE LAW.
AND SO WE'RE STRUGGLING BUT
THAT'S OUR OPINION AND ATTITUDE
AND CONTINUE TO PUSH FORWARD ON
THAT AS AGGRESSIVELY AS WE CAN.
THE INSTITUTE HAS ALSO MADE A
COMMITMENT TO THIS IN A
SIGNIFICANT WAY SO STAY TUNED.
>> SO SORRY.
TO FOLLOW-UP.
ALL THAT DATA, I UNDERSTAND IT'S
DIFFICULT BUT EVEN TO LOOK AT
THE STATE STUDY OR IF IT'S
DECLINED I THINK WOULD BE
HELPFUL.
>> WE'LL DO THAT.
>> THANKS, CARL.
QUICK QUESTION WITH THE C.R.,
WE'VE SEEN INTERIM PAY LINES FOR
RO1s AND OTHERS AND THERE'S NO
INTERIM PAY LINE FOR K AWARDS.
THEY'RE WAITING.
DO YOU ANTICIPATE MAKING A
DECISION BEFORE JANUARY OR THE
FULL BUDGET FOR Ks?
>> A LOT OF THESE THINGS WAIT
UNTIL THERE'S A FULL BUDGET
BEFORE WE MAKE DECISIONS.
>> OKAY, THANKS.
RUBEN.
>> I WANTED TO ASK SPECIFICALLY
ABOUT EARLIER STAGE
INVESTIGATORS WHICH RELATES TO
AUDREY'S POINT AS WELL.
COULD YOU GO BACK TO THOSE
NUMBERS.
I THINK THE RATES WERE HIGH BUT
I DON'T RECALL SEEING AN END.
IS THE NUMBER OF APPLICATIONS
DECLINING BECAUSE PEOPLE ARE
STUCK IN A HOLD HERE WITH COVID
OR ARE THEY TRYING --
>> IN '21 WE DON'T KNOW AND
AGAIN THIS IS NOT BROKEN DOWN BY
EARLY STAGE OR LATE STAGE OR
SENIOR.
>> IT WOULD BE NICE TO SEE THE
S.I. NUMBERS TOO.
>> I'LL PUT THAT IN OUR PLAN.
OUR FEAR IS A LOT OF THE YOUNGER
INVESTIGATORS HAVE DEPARTED TO
COMPANIES AND A LOT OF COMPANIES
ARE HIRING ALSO IN VIROLOGY AND
THAT COULD IMPACT OR E.S.I.
EFFORTS.
>> UNDERSTOOD.
WE FEEL THAT TOO, FRANKLY.
WE'VE BEEN LOSING PEOPLE TO
COMPANIES.
>> ALSO ABOUT Ks.
THE NUMBER OF K APPLICANTS, DO
YOU HAVE INFORMATION ON THAT?
>> NOT FOR THIS YEAR YET.
>> OKAY.
OTHER QUESTIONS?
>> MONICA.
>> ONE QUESTION IS THE BUILD
BACK BETTER INITIATIVE
INFRASTRUCTURE BILL, I'M
WONDERING IF THERE ARE THOUGHTS
WE COULD BRAIN STORM ON FOR
BUILDING BACK NEXT GENERATION
INVESTIGATORS?
I REMEMBER FIVE YEARS AGO WHEN
NIH LAUNCHED THE NEXT GENERATION
INITIATIVE, IT WAS MET WITH A
LOT OF ENTHUSIASM AT LEAST HERE
AT UCSF BECAUSE WHAT IT ENDED UP
DOING A LOT OF YOUNG
INVESTIGATORS APPLIED FOR THINGS
THAT WERE LOWER HANG AND COULD
DO THAT BEFORE THE RO1s AND
WONDER ABOUT ENCOURAGING
NON-INVESTIGATORS TO APPLY FOR
NON-R01s BEFORE THEY GET TO THE
R01s AND RELAUGHING --
RELEASING THE KP LINE MAY HELP
THEM RECOVER.
>> I THINK WHAT WE'RE STRUGGLING
WITH IS TRYING TO BALANCE
E.S.I.s WITH DIVERSITY AS WELL
WE HAVE A HIGHER PRIORITY TO
PROMOTE DIVERSITY OVER BLANKET
YOUNG INVESTIGATORS.
WE'LL HAVE TO SEE WHAT WE CAN
DO.
>> THANK YOU.
ANITA.
>> JUST TO ADD TO THE CHORUS,
YOU HEARD MY QUESTION TO FAUCI
AS WELL, I THINK THIS IS A
CRUCIAL ISSUE.
WE'RE SEEING THE CHALLENGE OF
RECRUITING TALENT AND HOW MANY
ARE BEING SWAYED FOR PAY AND
THEY'RE NOT GETTING FUNDED WITH
K AWARDS OR THE TRANSITION.
I HOPE WE CAN FIND WAYS TO
INCENTIVIZE AND PROMOTE NEW
PROGRAMS, NEW FUNDING STREAMS
AND GIVE SUPPLEMENTS THAT WILL
NOT TAKE A WHILE TO OBTAIN TO
GET PEOPLE BACK.
>> I THINK IT WOULD BE IMPORTANT
FOR YOU ALL TO WRITE A LETTER TO
MAUREEN ABOUT THIS.
>> THE LETTER TO MAUREEN TO OAR
WOULD BE HELP FFUL
>> I THINK AIDS IS A UNIQUE
SITUATION AND TO PUT EFFORT ON
THIS WOULD BE USEFUL.
THE OTHER IS IF YOU GOT COUNCILS
FROM OTHER INSTITUTES TO DO THIS
TOGETHER WITH YOU WOULD BE QUITE
IMPORTANT.
THAT WOULD BE MY SUGGESTION.
>> OKAY.
AND THE ONLY OTHER QUESTION I
HAVE IS FROM LAST TIME YOU
PRESENTED, I KNOW THERE'S A
DELAY IN GETTING DATA FOR US TO
REVIEW WHEN IT'S SEX
DISAGGREGATED IS THERE A
SOLUTION TO GET UPDATED DATA OR
REAL TIME DATA.
THIS IS GREAT HAVING THIS BUT
NOT SURE HOW MUCH GRANULARITY
WAS AVAILABLE.
>> THIS DATA WAS CLEANED AND
FINALIZED ABOUT A WEEK AGO.
IT TAKES A LONG TIME AT THE END
OF THE FISCAL YEAR AND WE CAN GO
BACK AND LOOK AT '20 AND THAT
WOULD BE WHERE WE WOULD BE.
IT BECOMES A HISTORY LESSON.
IT'S NOT REALLY USEFUL IN REAL
TIME AND THAT'S THE REALITY.
>> WE'LL TAKE THAT UP FROM THE
COMMITTEE AND NOTE TO MAUREEN.
>> THE IDEA IT'S NOT JUST US BUT
OTHER COUNCILS.
TRISH HAD HER HAND UP BUT PUT A
LINK IN THE CHAT TO AN OAR
DOCUMENT.
>> I JUST WANTED TO SAY, CARL,
THE EARLY STAGE INVESTIGATORS IS
ONE THING WE'VE BEEN WORKING ON
HARD FOR THE OAR AND WE HAVE ONE
SPECIAL COMMITTEE ONE HIV AND
COVID AND THERE'S BEEN WORK ON
THAT AND I LISTED RESOURCES
WE'RE PROVIDING AND THEY'RE
COLLECTING THIS INFORMATION OVER
THE ENTIRE NIH FOR EARLY STAGE
INVESTIGATORS.
I THINK MAYBE NEXT TIME WE
SHOULD GET BECAUSE MY UPDATE
DOESN'T INCLUDE THIS BECAUSE
IT'S ONE OF THE TASK FORCE BUT
MAYBE NEXT TIME IF YOU WANT TO
GIVE SOMEONE THAT KIND OF AN
UPDATE IT WILL BE OFFICIAL.
>> WE'LL PUT THAT IN THE MINUTES
AND FOLLOW-UP.
THANK YOU, TRISH.
IF THERE'S NO OTHER POINTS OF
DISCUSSION ON THIS WE'LL MOVE ON
TO SCIENTIFIC AND PROGRAMMATIC
UPDATES.
THIS HAS BEEN A GREAT YEAR.
083 AND O84 DELIVERED RESULTS
AND HAVE A LICENSED INJECTABLE
FOR PREVENTION USABLE BY
EVERYONE WHICH IS A REALLY
IMPORTANT STEP FORWARD.
HERE'S WHEN THEY OCCURRED IN
JULY THE MEN'S STUDY REPORTED
OUT IN NOVEMBER, THE WOMEN'S
STUDY POINTED OUT IN BOTH CASES
THEY ENDED UP BEING
STATISTICALLY SUPERIOR THOUGH IT
WAS A NON-INFERIORITY DESIGN
THAT CROSSED THE MARGIN AND
DEMONSTRATES SUPERIORITY IN BOTH
TRIALS WHICH IS JUST INCREDIBLE
TO GIVE A SENSE OF THE STRENGTH.
AND THE FDA MADE A DECISION AND
THE WAS WHEN THERE WAS SO MUCH
COVID NEWS IT DIDN'T EVEN MAKE
THE FRONT PAGE OF THE NEWSPAPER
AND IT'S GREAT TO HAVE IT
BECAUSE THEY CAN'T TAKE IT AWAY
FROM US NOW AND WE'RE ALSO
CONTINUING TO PUSH HARD ON
MAKING SURE SPECIAL POPULATIONS
CAN GAIN ACCESS.
WE'RE COMPLETING STUDIES IN
TEENS FOR AND WILL BRING THE AGE
OF USE DOWN WHICH IS IMPORTANT
AROUND THE GLOBE.
AND THERE'S ONE ON HOUSEHOLDS
TESTING AND THERE'S A STATIN
VERSUS STANDARD OF CARE.
FINISHING OUT THE STUDIES WE
NEED TO DO ON THE RING WE'RE
LOOKING AT AN OPEN-LABEL SAFETY
TRIALS TO PROVIDE THE DATA
NEEDED TO EXTEND USE AND WITH
705 NOT MEETING END POINTS, 706
HAS BEEN TOLD TO CONTINUE.
THE VACCINES ARE DIFFERENT IN
705 AND 706 AND WE'RE CONTINUING
THE STUDY AND SEE WHAT WILL
HAPPEN IN THE SPRING.
ON THE COVID FRONT, ACTIVE 2
CONTINUES TO BE A WORKHORSE FOR
OUT PATIENT STUDIES HAVING
DEMONSTRATED ACTIVITY FOR
BRE-BIO.
THE INTERFERON BETA IS ABOUT TO
OPEN AND WE'RE GETTING READY TO
OPEN A TRIAL WITH THE PROTEASE
INHIBITOR SO THINGS ARE MOVING
QUITE NICELY WITH ACTIV 2.
THE MONOCLONAL ANTIBODIES.
WE AT EUAs KEEPING IN MIND THE
LILLY GENERATION AND REGENERON
COMBINATION HAVE BEEN
ESSENTIALLY ELIMINATED BY
OMICRON.
THEY ARE BOTH COMPANIES ARE
WORKING ON OMICRON SPECIFIC BUT
BROAD ANTIBODY TO GET AN EUA
RE-ISSUED.
LILY IS STARTING THEIR STUDY AND
THE STATUS OF THE OTHERS ARE
LISTED THERE.
ON THE VACCINE FRONT, THE DATA
FOR THE BOOST CONTINUES TO GROW
AND PLEASED WHERE WE ARE IN THE
STUDIES AND IT'S IMPORTANT WE
START THINKING ABOUT NEXT
GENERATION AND MUCOSAL IMMUNITY
WELLS THE IMMUNITY WE GET GOOD
THE mRNA.
I THINK BEING ABLE TO GET
SIGNIFICANT ANTIBODY AND MUCOSAAL
SURFACE THE NOSE AND RESPIRATORY
TRACT ARE IMPORTANT.
THERE'S A RESEARCH PLAN BEING
DEVELOPED ON THE VACCINE FRONT
TO TAKE US TO THE NEXT
GENERATION.
NOW I NEED TO PRESENT THE SBIR
CONTRACT TOPICS FOR THE YEAR AND
THEN HAVE A VOTE ON THESE.
WE HAVE TWO NEW ONES.
THE PURPOSE IS THIS THERE'S A
PORTION OF THE SBIR FUNDING THAT
GOES OUT THROUGH GRANTS.
THE SBIR CONTRACTS ALLOWS THE
DIVISION TO THINK ABOUT WHAT THE
UNMET SCIENTIFIC PRIORITIES ARE
THAT COULD BE MET BY SMALL
BUSINESSES AND ENCOURAGE
SCIENTIFIC AND TECHNICAL
INNOVATION IN THESE SPECIFICALLY
IDENTIFIED AREAS.
THIS YEAR WE HAVE ONE NEW TOPIC
AND TWO FOR RE-ISSUE.
WE'LL TALK ABOUT THE ONE THAT'S
A NEW TOPIC.
THESE THE POINT OF CARE ONES AND
ADHERENCE ASSAYS AND THE SECOND
WAS LOOKING AT ASSAYS TO
DIFFERENTIATE HIV INFECTION FROM
THIS AND THOSE ARE BEING
REISSUED.
ONE OF THE THINGS IS IMPORTANT
IS WE BUILD A DATABASE THAT'S
BIGGER AND MORE INCLUSIVE THAN
WHAT WE'VE DONE IN THE PAST AND
THERE ARE SO MANY VIRUSES AND
STUDIES BEING ABLE TO TRACK THIS
THAT CATEGORIZES THE STRAINS,
YUM RESPONSES, THE KINDS OF
THINGS DONE WITH THOSE WOULD
BENEFIT THE FIELD BECAUSE WE'RE
NOT THE ORGANIZATION WHO USES
NON-PRESUME AN PRIMATES AND
WE'RE LOOKING TO GET THIS STOOD
UP AS AN SBIR OR CONTRACT.
THIS IS TO ESTABLISH A PROJECT
TEAM TO FIND THE CRITICAL DATA
WE WISH TO COLLECT.
DEVELOP IT INTO SOFTWARE PACKAGE
BUT ALSO DEVELOP THE TOOLS AND
TECHNOLOGIES TO GO OUT AND GET
THE DATA AND CURATE AND THINK
ABOUT THE RE-AGENT PROGRAM WITH
THE ABILITY TO HAVE STRAINS AND
APPROPRIATE RE-AGENTS WILL HELP
BRING A LEVEL OF QUALITY CONTROL
TO THE FIELD AND ULTIMATELY
CREATE A WEBSITE FOR USER ACCESS
AND USE.
ALSO CONTINUE TO CURATE
LITERATURE.
I THINK IT WOULD BE INCREDIBLY
VALUABLE TO THE FIELD.
WE'LL STOP THERE AND WHILE YOU
ALL ARE VOTING WE CAN TAKE A FEW
MORE QUESTIONS.
>> IF PEOPLE COULD VOTE THAT
WOULD BE GREAT.
ANY ADDITIONAL QUESTIONS FOR
CARL?
>> I DON'T HAVE A QUESTION BUT
COMMENT AS A NON-HUMAN PRIMATE
RESEARCHER I'M GLAD YOU'RE
PROVIDING THIS INFORMATION AND
COLLECTING THAT.
I THINK THAT'S GOING TO BE A
GREAT RESOURCE TO THE FIELDS.
I'M VERY SUPPORTIVE OF THAT.
THANK YOU.
>> THANKS, TRISH.
>> ALL RIGHT, WELL, SHALL WE GO
ON THEN?
>> LET'S NOVE TRISHA'S SLIDES
AND WHAT SHE'S GOING TO PRESENT.
>> RIGHT, TRICIA BURDO WITH THE
UPDATE.
>> THANK YOU.
I FIRST WANT TO APOLOGIZE FOR
NOT BEING ON SCREEN TODAY AND
BEING A LITTLE HOARSE.
I ACTUALLY HAVE COVID.
I'LL START NOW.
WE THAT'D 58th MEETING OF THE
OARAC HELD VIRTUALLY AND THIS
FEATURED A REPORT FROM THE
DIRECTOR AND UPDATES FROM THE
HIV, ARB AND OAI WORKING GROUPS
AND PRESENTATION FROM THE CDC
DIRECTOR AND UPDATE FROM THE
WHITE HOUSE OFFICE OF NATIONAL
AIDS POLICY.
SO THE KEY OAR STRATEGIC
ENGAGEMENTS INCLUDED WERE 48
DOMESTIC SESSIONS THAT HAD BEEN
HELD SINCE 2008, A SUMMARY
REPORT WILL BE AVAILABLE ON
OAR'S WEBSITE SOON FOR THAT.
A REPORT OF NIH, EHE ACTIVITIES
IN FY19 DEVELOPED BY THE NIH
AIDS EXECUTIVE COMMITTEE ALSO
AVAILABLE ON OAR WEBSITE.
WE ALSO HAD STRATEGIC
ENGAGEMENTS WITH CONGRESS, THE
WHITE HOUSE, HHS AND OTHER
LEADERS AT THE NIH AND THIS
INCLUDES THE FY22 CONGRESSIONAL
BUDGET AND NIH REPRESENTATION
AND ON THE STEERING COMMITTEE.
FY22 AIDS PROFESSIONAL BUDGET IS
AVAILABLE ON THE OAR WEBSITE FOR
REVIEW.
PER LEGISLATION, THE PJ
ESTIMATES FUNDING NECESSARY TO
CARRY OUT NIH RESEARCH WITHOUT
REGARD TO THE PROBABILITY THAT
SUCH AMOUNTS WILL BE
APPROPRIATED.
SO THE FY2022 PJ BUDGET IS
$3.875 BILLION AN INCREASE OF
25% OVER THE FY2021 ESTIMATE.
.
SO DR. GOODNOW DISCUSSED NEW
MEMBERS WE HAVE TWO NEW AD HOC
MEMBERS.
DR. METHS AND DR. TURNBULL.
SO THE CDC DIRECTOR AND FORMER
OAR CHAIR DR. WOLINSKI OUTLINED
THE ROLE AND HOW THE CDC PLANS
TO ADDRESS EACH PILLAR TO
DIAGNOSE, TREAT, PREVENT AND
RESPOND.
ACROSS EACH PILLAR SHE STRESSED
SOCIAL FACTORS THAT ACT AS
BARRIERS TO IMPROVEMENT.
WE HAD MR. HAROLD PHILLIPS OF
THE OFFICE OF NATIONAL AIDS
POLICY WHO DISCUSSED BIDEN
ADMINISTRATION'S SUPPORT AND YUM
DATES TO THE NATIONAL HIV
STRATEGY AND INTERAGENCY
COLLABORATION.
ALL THE MEETING MINUTES ARE
AVAILABLE ON THE WEBSITE AND THE
NEXT MEETING WILL BE FEBRUARY 24
AGAIN VIRTUAL AND ALSO HAVE AN
ORIENTATION SESSION FOR THE NEW
MEMBERS ON THE 23rd.
THAT'S IT.
THE ONE THING I SKIPPED OVER
LAST WAS WE HAD UPDATES FROM THE
TWO PANELS OF THE WORKING
GROUPS.
AGAIN, THIS IS ALL DETAILED FROM
OAR IN THE HIV INFO GROUP.
THAT'S IT.
THANK YOU.
>> I APPRECIATE ALL THE OUTREACH
AND LISTENING.
IT'S FANTASTIC.
ANY QUESTIONS?
>> WE'LL START WITH THE BASIC
SCIENCES PROGRAM AND DIANA
FINZI.
>> GOOD AFTERNOON, EVERYONE.
GOOD TO SEE YOU ALL.
SO TODAY I'LL GIVE YOU AN
OVERVIEW OF THE BASIC SCIENCES
PROGRAM.
SO LAST YEAR I SPENT A FEW
MINUTES TALKING ABOUT THE IMPACT
THAT SARS HAD ON OUR HIV WORK.
THIS YEAR I'LL MENTION THE
IMPACTS AND GIVE HIGHLIGHTS AN
MENTION ANTICIPATED PRIORITIES
AND FUTURE DIRECTS AND THE
FUTURE INITIATIVE PROPOSALS
PRESENTED AT FUTURE MEETINGS
WITH YOU.
SO MUCH OF WHAT WE AS THE BASIC
SCIENCES PROGRAM DO IS SUPPORT
THE REALLY EARLY STAGE SCIENCE.
THE EARLY INDICATIONS OF WHAT
MIGHT EVENTUALLY LEAD TO BREAKS
THROUGH.
OUR FOUNDATION ARE IN A LARGE
NUMBER OF UNSOLICITED GRANTS AND
ALSO SOLICIT GRANTS IN ORDER TO
INDICATE DIRECTION AND AREAS.
WE WORK WITH OTHER PROGRAMS AND
THERAPEUTICS AND PREVENTION AND
VACCINES AND WE OFTEN SEE OUR
EARLY WORK IMPROVE IN THOSE
AREAS.
THE SPACE IS IN BETWEEN PROGRAMS
CONTINUE TO BE A VERY IMPORTANT
AREA IN THE BASIC SCIENCES
PROGRAM AS WE WORK TO LEVERAGE
RESOURCES WHEN WE THINK WORKING
TOGETHER WILL LIKELY BRING
INSIGHT AND ADVANCES.
AS AN EXAMPLE THAT I'VE GIVEN
BEFORE THAT YOU HEARD BEFORE, WE
ENCOURAGE AND SUPPORT
INVESTIGATORS WHO USUALLY WORK
ON VACCINES TO FOCUS ON HIV
CURE.
REGARDLESS, OUR MAIN FOCUS
CONTINUES TO BE GENERATING NEW
IDEAS, SUPPORTING A WIDE BASE OF
EXPLORATION AND FEEDING THE
PIPELINE WITH DIVERSITY OF
PROJECTS.
SO I HOPE TO GIVE YOU A FEEL FOR
THE GREAT BREADTH OF WHAT WE DO
IN THE BASIC SCIENCES PROGRAM.
OUR PROGRAM IS THE PATHOGENESIS
AND BASIC RESEARCH BRANCH, THE
TARGETED INTERVENTIONS BRANCH
AND THE EPIDEMIOLOGY BRANCH.
DEBT COLLECTIVELY WE OVERSEE
550 GRANTS WITH AN ANNUAL BUDGET
OF AROUND $380 MILLION AND
CONTRACTS THAT PROVIDE SERVICE
TO GRANTEES.
AN EXAMPLE IS THE AIDS RE-AGENT
PROGRAM YOU ALL KNOW AND LOVE.
THE FOCUS IN BASIC SCIENCE IS
MECHANISTIC WORK WITH ATTENTION
TO LATENCY PERSISTENCE AND CURE
AND TARGETED INVENTIONS WE HAVE
AN INCREASE FOCUS ON
NON-TRADITIONAL THERAPEUTICS
SUCH AS GENE AND CELL-BASED
THERAPIES AND BIOLOGICS AND RNA
THERAPEUTICS AND ALSO CONTINUE
TO WORK ON SPECIFIC INTERVENTION
TO VALIDATE HIV TARGETS AND
SMALL-MOLECULE INHIBITERS.
IN EPIDEMIOLOGY, WE MAINTAINED
WORK ON CLINICAL OUTCOMES OF HIV
THROUGH LARGE COHORTS THROUGHOUT
THE WORLD AND ELECTRONIC HEALTH
RECORD RESEARCH.
RECENTLY FOCUSSING MORE ON
TUBERCULOSIS AND THE
INTERSECTION OF T.B. AND HIV.
THE EPIDEMIOLOGY BRANCH HAS ALSO
EXPANDED SUPPORT OF NEW
SURVEILLANCE APPROACHES TO
IDENTIFY PEOPLE WHO ARE AT HIGH
RISK OF INFECTION AND PEOPLE WHO
ARE AT RISK OF INADEQUATE
TREATMENT.
THEN A RELATIVELY NEW AREA LED
BY OUR TEAM IS THE NIH ROLE IN
THE FEDERAL PROGRAM OF ENDING
THE HIV EPIDEMIC.
WE HAVE ESTABLISHED A
PARTNERSHIP WITH OUR COLLEAGUES
WITHIN THE NIH SO THE NATIONAL
INSTITUTE OF MENTAL HEALTH AND
THE OFFICE OF AIDS RESEARCH AS
WELL AS WITH OUTSIDE AGENCIES
SUCH AS THE CDC AND HRSA.
OUR EFFORTS RESULTED IN BETTER
ALIGNMENT ACROSS AGENCIES.
YOU CAN SEE THE BREADTH OF THE
WORK WE DO IS QUITE GREAT.
IT RANGES AT SUBSCIENCE TO
EPIDEMIOLOGY AND DOOIM
DYNAMICS OF HIV TRANSMISSION
BETWEEN PEOPLE.
I HAVE GIVEN A BROAD OVERVIEW
AND NOW WANT TO TOUCH ON
HIGHLIGHTS.
AS I MENTIONED LAST YEAR WE WERE
DEEPLY ENGAGED IN SUPPORTING OUR
COLLEAGUES IN THE DIVISION OF
MICROBIOLOGY AND INFECTIOUS
DISEASES.
I NOTED WE WERE INVOLVED IN MANY
NIH ACTIVITIES INCLUDING THOSE
THAT ARE LISTED HERE.
MOST IMPORTANTLY, EVERY MEMBER
HAS CONTRIBUTED BEHIND THE
SCENES WITH UNQUALIFIED
ENTHUSIASM IN PROVIDING THE
REQUESTED ASSISTANCE AT THE DROP
A HAT.
I'LL BEEN PROUD OF MY GROUP
DURING THIS EXTRAORDINARY TIME.
SO SIMILARLY, WE SAW OUR
GRANTEES RISE TO THE OCCASION
WITH AN OUTPOURING OF EAGERNESS
TO CONTRIBUTE.
I WANT TO GIVE ONE OF MANY
EXAMPLES.
MEMBRANE PROTEIN STRUCTURES ARE
A BIG CHALLENGE TO STUDY OWING
TO THEIR PARTIALLY HYDROPHOBIC
SERVICES.
THE BREAKTHROUGH CAME IN 2002
FROM THE LAB AT THE UNIVERSITY
OF ILLINOIS WITH THE DEVELOPMENT
OF THE LIPID BIO LAYERS 8 TO 16
NANO METERS IN DIAMETER IN
SOLUTIONS BY THESE TWO
ENCIRCLING ANDO PATHIC SCAFFOLD
PROTEINS.
THESE STRUCTURES CREATE A NATIVE
LIKE MEMBRANE ENVIRONMENT TO
ANCHOR PROTEINS AND ALLOW THE
STUDY OF FULL LENGTH MEMBRANE
PROTEINS.
SO ONE OF OUR GRANTEES FROM
HARVARD MEDICAL SCHOOL HAS BEEN
USING THESE NANO DISCS FOR HIV
STRUCTURES AND HERE ON THE
BOTTOM LEFT IS AN EXAMPLE OF HIV
ENVELOPE EMBEDDED IN THE NANO
DISC AND NEXT TO IT THE SAME
PROTEIN WITH AN ANTIBODY BOUND
IT.
WITH SARS HE WAS ABLE TO DO THIS
AND HE PUBLISH THE SPIKE
PROTEIN.
THERE'S PREFUSION STATE ON THE
LEFT OF THE SPIKE PROTEIN AND
THE POST-FUSION THAT OCCURS WHEN
IT BINDS AND FUSES.
THE RECEPTOR BINDING DOMAIN ON
TOP HERE BINDS AND OPENS UP AS
PART OF THIS SPIKE FALLS OUT AND
IN THIS PUBLICATION, THEY
REPORTED A SIGNIFICANT
ACCUMULATION OF THIS POST-FUSION
STRUCTURE WHICH CAN HAPPEN
SPONTANEOUSLY.
AND IF IT HAPPENS BEFORE
PREFUSION THEY'RE NOT FUNCTIONAL
FOR ENTRY.
AS VARIANTS EMERGED HE WAS ABLE
TO APPLY THE SAME TECHNOLOGY AND
MAKE MANY CRITICAL DISCOVERIES
AND MENTOR SOME HARD-WORKING
POST-DOC.
YOU CAN SEE THE LIST THERE OF
THE PAPERS THAT THEY PUBLISHED
AND ARE PUBLISHING.
SO IN THE NEXT SLIDE, I CAN SHOW
YOU THE VERY SIMPLE CHANGE TO
DESCRIBE AND THAT'S A CHANGE OF
ONE AMINO ACID FROM THIS ACID TO
GLYCINE ON AMINO ACID 614,
ROUGHLY HALFWAY THROUGH THIS
PROTEIN.
IT'S JUST UNDER 1300 AMINO
ACIDS.
YOU PROBABLY RECALL ONE OF THE
FIRST VARIANTS BEING THE D TO G
MUTATION THAT RAPIDLY BECAME
DOMINANT GLOBALLY EARLY IN 2020.
SO WHEN THE GROUP MADE THIS ONE
AMINO ACID CHANGE FROM B TO G
THEY SAW THE TITER HOLDING IN
THIS LOOP, THE 630 LOOP WHICH
ALSO RESULTED IN GREATER
STABILITY OF THIS COMBINED
STRUCTURE WITH THE RECEPTOR
BINDING DOMAIN UP FORMATION AND
LESS STRUCTURES INDICATING THE
SINGLE AMINO ACID STABILIZED
THIS PREFUSION STAY.
THEY WERE THERE BE ABLE TO GIVE
A MECHANISTIC EXPLANATION
SHOWING THE ONE AMINNOW -- AMINO
ACID STRAIN LESS PRONE TO
MISFIRING BEFORE BINDING TO THE
DOMAIN AND REDUCED THE PREMATURE
S1 SHEDDING AND INCREASING THE
NUMBER OF TOTAL FUNCTIONAL S
PROTEINS INCORPORATED.
THISAND REDUCED THE PREMATURE S1
SHEDDING AND INCREASING THE
NUMBER OF TOTAL FUNCTIONAL S
PROTEINS INCORPORATED.
THIS THIS GAVE THE VIRUS HIGHER
CHANCE TO INFECT.
NOW GOING BACK TO THE HIV WORK
AND HIGHLIGHTS.
I TOUCHED ON ONE HIGHLIGHT THE
SARS HIGHLIGHT HAVING TO DO WITH
STRUCTURES AND MOLECULES SO FOR
THE SAKE OF TIME ONLY ONE
EXAMPLE ON THE LEVEL OF CELLULAR
BIOLOGY AND ONE ON THE HUMAN
SCALE OF EPIDEMIOLOGY.
SO WE HAVE A PROVIRUS UNAFFECTED
BY ANTIRETROVIRAL THERAPIES AND
INVISIBLE TO THE IMMUNE SYSTEM
AND THIS GRAPH SHOWS THE
STABILITY OF THE FREQUENCY OF
LATENTLY AFFECTED CELLS IN
TREATED PEOPLE OVER TIME.
EACH COLOR IS A DIFFERENT
PERSON'S TRAJECTORY WITH A
BALANCE BETWEEN
SELF-PROLIFERATION AND -- CELL
PROLIFERATION AND CELL DEATH AND
YOU CAN SEE SOMETIMES THERE'S AN
INCREASE IN THE LATENT RESERVOIR
SO THE QUESTION IS WHAT CAN
CAUSE THE LATENT CELLS TO
PROLIFERATE RESULTING IN A
LARGER VIRAL HOUSING.
THERE'S FOUR POSSIBLE MECHANISMS
THAT EACH NEED TO SEE THE
PROLIFERATION.
THE VIRUS IS CARRIED OVER TO THE
PROGENY.
WE HAVE A CD4 CELL WITH THE
PROVIRUS DIVIDES SPONTANEOUSLY
OR SOMETIMES IN RESPONSE TO
CYTOKINES AND PROLIFERATION IS
NON SPECIFIC.
ON THE BOTTOM WE HAVE TWO
DIFFERENT MECHANISMS WHEREBY A
SPECIFIC CLONE CAN DIVIDE.
HERE, A CLONAL POPULATION IS
DRIVEN BY TWO DISTINCT
MECHANISMS.
A SPECIFIC T CELL RECEPTOR OR
PRO-VIRUS INTEGRATED AT THE
SPECIFIC SITE.
ON THE LOWER LEFT ARE DIFFERENT
T CELLS WITH A DIFFERENT
RECEPTOR THIS IS SPECIFIC TO THE
POPULATION.
ON THE RIGHT THERE'S THREE CELLS
WITH PROVIRUS INTEGRATED IN
THREE SITES ON THE CHROMOSOMAL
DNI.
ONE IS INTEGRATED AN SITE THAT
CELL DIVISION HAPPENS MORE
FREQUENTLY.
IN THIS CASE THE DYNAMIC IS
SPECIFIC TO THIS PARTICULAR
INTEGRATED PROVIRAL CLONAL
POPULATION.
TO REPEAT, WE HAVE CLONAL
PROLIFERATION ON THE LOWER LEFT
THAT'S SPECIFIC TO A PARTICULAR
T CELL RECEPTOR AND ON THE LOWER
RIGHT THAT IS SPECIFIC TO A
PARTICULAR PROVIRAL INTEGRATION
SITE.
WE LEARNED ABOUT T CELL RECEPTOR
MODE OF PROLIFERATION FROM
SEVERAL PUBLICATIONS INCLUDING
ONE WHERE THEY COMBINED FOUR
EXPERIMENTAL METHODS.
THE ASSAY AND T CELL RECEPTOR
SEQUENCING AND VIRUS SPECIFIC
PEPTIDE STIMULATION OF CD4
CELLS.
DISREGARD THE HIV INFECTION AND
COLOR.
IT DEPICTS WHAT HAPPENS AFTER
THE T CELL ENCOUNTERS THE
ANTIGEN SHOWN AS THE BLACK
DASHED LINES.
THE INITIAL ONE IS SMALL WITH
THE FIRST ROUND OF ANTIGEN
STIMULATION THE POPULATION
INCREASES DUE TO CELL DIVISION
AND THEN CONTRACTS AND A STABLE
MEMORY POPULATION IS LEFT AS
ANTIGEN IS CLEARED.
WHEN THE MEMORY POPULATION
ENCOUNTERS THAT ANTIGEN AGAIN,
IT FURTHER PROLIFERATES.
THIS IS NORMAL IMMUNE SYSTEM
PHYSIOLOGY WHERE CELLS
PROLIFERATE WITH EXPOSURE TO THE
COGNATE.
NOW WHICH IS WHAT HAPPENS IN THE
PRESENCE OF HIV IN ORANGE.
ON THE LEFT IT SOME CELLS GET
INFECTED WITH HIV.
THE INITIAL HIV INTEGRATION
EVENT IS SHOWN BY THE ORANGE
ARROW.
NOT ALL THESE MEMORY CELLS GET
INFECTED WITH HIV.
THE T CELL RECEPTOR CLONAL
POPULATION THERE ON THE LEFT IS
MIXED SOME INFECTED CELLS
DEPICTED IN ORANGE AND SOME
REMAINING UNAAFFECTED --
UNAFFECTED IN RIGHT AND SHORTLY
AFTER THE CD4 CELL ENCOUNTERS
ANTIGEN IT'S INFECTED WITH HIV.
INSTEAD IN THIS CASE THE
INTEGRATION OCCURRED EARLY AFTER
THE CELL SAW ANTIGEN.
IN THIS CASE ON THE RIGHT, ALL
OF THE FUTURE PROGENY OF THE T
CELL RECEPTOR CLONE WILL CARRY
PROVIRUS.
IT'S THROUGH THESE TYPES OF
STUDIES WE'RE GATHERING A BER
INFORMATION OF BIOLOGY OF WHAT
DRIVES HIV PERSISTENCE.
SO NOW MOVING ON TO THE
POPULATION LEVEL HIGHLIGHT, WE
HAVE AN EXAMPLE OF AN IMPORTANT
BINDING FROM OUR LIMITED
INTERACTION TARGETED
EPIDEMIOLOGY GRANTS THE ACRONYM
LITE AND THIS IS LOOKING AT HIV
INFECTION IN THE UNITED STATES.
SO THIS PAPER WITH THE TITLE THE
CRISIS WE'RE NOT TALKING ABOUT
ONE IN THREE HIV CONVERSIONS
AMONG SEXUAL AND GENDER
MINORITIES WERE PERSISTENT
METHAMPHETAMINE USERS DESCRIBES
A STUDY ENROLLED OVER 36,000 MSM
WITH 5,000 COMPLETING BASELINE
AND NEAR YEAR FOLLOW-UP STUDIES
AND THE AUTHORS FOUND THAT HIV
VULNERABILITY INTERSECTS WITH
METH USE.
THEY WERE STRIKING SEVEN FOLD
INCREASE RISK OF HIV COMPARED TO
NON-USERS.
AMONG OTHER IMPORTANT FINDINGS
THEY FOUND BLACK MSM WERE THREE
TIMES INCREASED RISK COMPARED TO
WHITE MSM.
NOW FOCUSSING NOW I WANT TO
FOCUS ON FUTURE DIRECTION AND GO
BACK TO THE STUDIES AGAIN AND WE
HAVE RECEIVED APPLICATIONS FOR
THE CENTERS FOR HIV STRUCTURAL
BIOLOGY.
YOU MAY RECALL THESE CENTERS
WERE TRANSFERRED FROM NIGMS TO
NIAID TWO YEARS AGO AND WE'RE
SUPER EXCITED TO SEE THE RESULTS
OF THE REVIEWS AND THE FUTURE
STUDIES THAT WILL BE FUNDING
UNDER NIAID.
ALSO VERY EXCITING FOR US, IN
2021 WE WERE ABLE TO INCREASE OF
OUR FLAGSHIP FUNDING FOCUSSED ON
FIND CURE FOR HIV AND INCREASED
THE NUMBER OF MARTIN DELANEY
COLLABORATORIES TO 10 GROUPS.
THE SIX NEW ONES HAVE THE DARKER
BACKGROUND AND WITH THE
EXPANSION WE'VE BEEN ABLE TO
INCREASE THE RATIO OF FEMALES TO
MALES IN LEADERSHIP POSITIONS.
WE NOW HAVE 10 FEMALES IN BOLD
AND 15 MALES.
TO GIVE ONE EXAMPLE OF A FUTURE
SCIENTIFIC DIRECTION HOUSED
WITHIN THE MARTIN DELANEYS AS
WELL AS OTHER AWARDED GRANTS, WE
HAVE GENE THERAPY STUDIES AIMED
AT CURING HIV.
AMONG THE STRATEGIES WE AIM TO
GENERATE RESISTANT CELLS AND
ENHANCE HIV CELLULAR IMMUNE
RESPONSES, DIRECTLY TARGET PRO
VIRUS AND ALSO FIND EFFECTIVE
WAYS TO DELIVER BIOLOGICAL
MOLECULES.
NOW, TO GAIN ADDITIONAL STRIDES
IN THIS AREA, WE HAVE JOINED
FORCES WITH THE NATIONAL
INSTITUTE OF HEART, LUNG AND
BLOOD AS WELL AS THE NIH OFFICE
OF THE DIRECTOR.
SO NOW MOVING ON TO
EPIDEMIOLOGY.
WE WILL CONTINUE THROUGH OUR
CENTERS FOR AIDS RESEARCH, OUR
ACTIVE PARTICIPATION IN THE
ENDING THE HIV EPIDEMIC
INITIATIVE.
OUR ROLE AT THE NIH, IS TO
DETERMINE HOW BEST TO GET
EFFECTIVE PREVENTION AND
TREATMENT TOOLS TO THE PEOPLE
THAT NEED THEM THROUGH
IMPLEMENTATION RESEARCH IN
COLLABORATION WITH COMMUNITY
PARTNERS.
AND TO DEVELOP GENERALIZABLE
KNOWLEDGE FROM LOCAL KNOWLEDGE
TO OPTIMIZE IMPLEMENTING BEST
PRACTICES.
NOW, THIS SLIDE SUMMARIZES OUR
FUNDING TO DATE FOR SUPPORT TO
THE EHE INITIATIVE THROUGH THE
NIH AND THE FUNDING
ANNOUNCEMENTS WERE DEVELOPED IN
COLLABORATION WITH CDC AND HRSA
COLLEAGUES.
I WANT TO DRAW YOUR ATTENTION TO
THE 2021 WHERE WE FUNDED 36
AWARDS TO ADDRESS THE EHE
PRIORITIES THAT MEET THE LOCAL
NEEDS AND INVOLVE COLLABORATION
WITH IMPLEMENTING PARTNERS SUCH
AS THE HEALTH DEPARTMENTS AND
RYAN WHITE CLINICS.
A QUARTER INVOLVE THE
PARTNERSHIP WITH THE
HISTORICALLY BLACK COLLEGES AND
UNIVERSITIES AND
MINORITY-SERVING INSTITUTIONS.
SO ALSO IN THE AREA OF
EPIDEMIOLOGY, WITH U.S. BASED
FOCUSSED EPIDEMIOLOGY AS WE
DISCUSSED THE LITE APPLICATION
MOSTLY ON MSM, WE WERE ASKED
WHAT WE WERE DOING GAIN
INFORMATION ON WOMEN WITH
PARTICULAR CONCERN FOR MINORITY
WOMEN.
THIS IS FOCUSSED ON THE EPIDEMIC
AMONG WOMEN IN THE UNITED STATES
AND HAS RECEIVED SUPPORT ACROSS
NIH INSTITUTES AND OFFICES.
SIMILAR TO THE LITE INITIATIVES
FOR MSM, WE USE DIGITAL
APPROACHES TO ENROLL, RETAIN AND
ANALYZE INDIVIDUAL DATA TO HELP
IDENTIFY WOMEN VULNERABLE TO HIV
AND FIND NOVEL WAYS TO REDUCE
THIS VULNERABILITY.
FINAL
FINALLY MY LAST EXAMPLE IS ON
THE GLOBAL SCALE AND DATABASE TO
EVALUATE AIDS IT'S A CONSORTIUM
THAT COLLECTS DATA ON OVER 2
MILLION PATIENTS AT 430 CLIN
INNINGS AROUND THE WORLD.
IN ADDITION TO -- CLINICS AROUND
THE WORLD IN ADDITION TO
TREATMENT AND OUTCOMES THEY
CONTINUE TO GROW THEIR DATA
SCIENCE SKILLS IN THE EASE OF
MOVING DATA FROM THE CLINIC TO
ANALYSIS.
THE RECENT ADDITION OF SITE ARE
FOCUSSED ON SPECIFIC POPULATIONS
SUCH AS ADOLESCENTS, YOUNG ADULT
OR CHILDREN TO MEASURE FACTORS
ON A MORE GRANULAR LEVEL.
TOE SUMMARIZE IN THE BASIC
SCIENCES AND TARGETED
INTERVENTIONS WE AIM TO
STRENGTHEN AND RE-INVIGORATE
WORK ON STRUCTURAL VIROLOGY AND
IMMUNOLOGY ON ELIMINATING
RESIDUAL RESERVOIRS.
IN EPI, WE'RE PARTNERING WITH
OTHER INSTITUTES ON OUTCOMES AND
GAINING AN INCREASE IN
UNDERSTANDING TRANSMISSIONS AND
SUPPORT STUDIES TOWARDS EHE.
I WANT TO END BY THANKING MY
COLLEAGUES AND AGAIN EXPRESSING
MY APPRECIATION AND WORKING WITH
A WONDERFUL GROUP OF COMMITTED
PEOPLE.
AND FOR A MOMENT I'D LIKE YOU TO
FOCUS YOUR ATTENTION ON THE
THREE PEOPLE IN THE UPPER RIGHT
HAND CORNER.
I WANT TO THANK ANN AND JASON
WHO HELP US STAY FOCUSSED AND
TONY WHO AFTER 17 YEARS OF TRULY
OUTSTANDING SERVICE WILL RETIRE
NEXT MONTH.
WE WILL MISS HIM AN HIS DEEP AND
BROAD KNOWLEDGE ABOUT HIV.
THANK YOU ALL FOR YOUR ATTENTION
AND I'M HAPPY ANSWER ANY
QUESTIONS.
>> THANK YOU.
THAT WAS GREAT.
IT'S GREAT TO SEE AWARE AT THIS
POINT AND MANY REMEMBER THE
DISCUSSION WE WERE IMPRESSED AS
PEOPLE DESCRIBED LITE AND THEN
WE SAID WHAT ABOUT WOMEN AND
WOMEN OF COLOR AND THE
DISCUSSION STARTED AND YOU SAID
WE'
WE'RE THINK ING ABOUT IT AND WE
ARE NOT PEOPLE WHO NEED
IMMEDIATE GRATIFICATION AND IT'S
GREAT TO SEE IDEAS TURN INTO
PROPOSALS AND RESULTS.
THANK YOU.
QUESTION S FOR DIANA?
>> THAT WAS AN AMAZING
PRESENTATION AND HUGE AMOUNT OF
WORK.
I AM FROM THE CDC FROM THE
PUBLIC HEALTH PERSPECTIVE THANK
YOU FOR THE WORK YOU'RE DOING IN
THE EPIDEMIOLOGY SPACE.
IT'S CRITICAL AND WANTED TO ASK
A FOLLOW-UP ABOUT THE ROLE OF
THE METHAMPHETAMINE STUDY AND
ONE OF THE STRESSES IS WE DON'T
HAVE INTERVENTIONS TO DO FOR
PEOPLE ON METHAMPHETAMINES AND I
KNOW IT'S OUTSIDE THE ZONE OF
WHAT WE DO EVERYDAY BUT
SOMETHING WE TALK ABOUT AT CDC
AS WHAT WE CAN DO TO PUSH OTHER
RESEARCH SIMILAR TO WHAT WE KNOW
ABOUT OPIOIDS.
IS THERE ANY AWARENESS OF NEXT
STEPS AND MAYBE NOT OURS BUT
ONES WE CAN FACILITATE.
I'M OBSESSED WITH THIS TOPIC
BECAUSE WHAT DO WE OFFER ON THE
PUBLIC SIDE OF THE WORLD AND THE
ANSWER IS NO REALLY GOOD
INTERVENTION BUT I'D LOVE YOUR
THOUGHTS.
THANK YOU.
>> THANK YOU.
MOSTLY THANK YOU TOO FOR BEING
THERE AT THE CDC.
I ENJOY COLLABORATING WITH YOU.
THING THERE THING WAS
DISCOVERING THAT AND SHOWING
THAT ASSOCIATION.
THOUGH WE'RE NOT PRIMARILY
RESPONSIBLE THERE, WE'RE
PARTNERING REALLY WELL WITH OUR
COLLEAGUES IN NIDA WHO SEEM TO
BE REALLY INTERESTED IN THIS
FINDING.
I SEE CARL HAS HIS HAND UP.
>> IN THE DISCUSSION WITH THE
BUDGET TODAY, ONE OF THE AREAS
NIDA IS GETTING A BIG INCREASE
IN IS SPECIFICALLY TO TARGET
METHAMPHETAMINE USE.
IT'S RECOGNIZED AS A SIGNIFICANT
PROBLEM AND NORA AND THE TEAM
HAVE BEEN TRYING AND WE'LL SEE
WHAT WE CAN DO.
>> HAPPY TO OFFER IF YOU NEED A
PUBLIC VOICE.
I'M HAPPY TO BE PART OF THAT
CONVERSATION.
>> I THINK THEY ARE VERY AWARE.
WE'VE HAD FOR A VARIETY OF
REASONS WE'VE HAD MEETINGS WITH
THEM ABOUT ANTIBODIES THAT WOULD
BIND AMPHETAMINES AND THEY'RE
LITERALLY TRYING TO PUSH EVERY
BUTTON AT THIS POINT.
WE'LL CONTINUE TO WORK WITH THEM
AND ALSO GO OLD FASHIONED
ACTIVITIES THAT CAN REACH INTO
COMMUNITY AND DO THE KIND OF
CLINICAL INTERVENTIONS ARE ALL
WE HAVE RIGHT NOW THIS IS AN
EXAMPLE OF WHERE STUDIES LIKE
ARE GOING ON IN THE CITY HERE
WHERE THERE'S AN INTERVENTION
CAN YOU FIRST INTERVENE WITH SAY
PREP AND GET SOMEBODY ON PREP
AND THEN WORRY ABOUT HAVING THEM
TRITATE OFF THEIR AMPHETAMINE
AND THE GATEWAY DRUG LIKE PREP
IS AN INTERESTING CONCEPT.
>> THANKS.
>> COULD THERE BE VIROLOGY
UNDERLYING THIS BEHAVIOR?
>> NIDA HAS PROGRAMS IN RECEPTOR
DENSITIES AND THINGS LIKE THAT.
>> THANKS.
>> THAT STUDY LOOKED AT
BEHAVIOR.
>> ANY OTHER QUESTIONS?
>> MONICA HAS HER HAND UP.
>> THANK YOU FOR GOING OVER THE
LITE PREP WORK BECAUSE THAT'S
IMPORTANT AND WONDERING THE LITE
TREATMENT GRANTS WE TALKED ABOUT
LAST TIME AT OARAC ARE GOING TO
BE LAUNCHED SOON BECAUSE THEY'RE
COMPLEMENTARY AT GETTING AT THE
LAST 10% NON-VIROLOGICALLY
SUPPRESSED GROUP.
>> YES, WE'RE WORKING ON THAT
AND WILL HOPEFULLY HAVE RESULT
TO REPORT AT ONE OF THESE NEXT
MEETINGS.
>> ANITA.
>> THANK YOU, WONDERFUL WORK YOU
AND YOUR TEAM ARE DOING.
QUESTIONS ABOUT THE IDEA
CONSORTIUM BECAUSE I THINK IT'S
A REAL OPPORTUNITY FOR GETTING
IMPORTANT EPIDEMIOLOGICAL DATA
AND ADDING ON A BIO SPECIMEN
COLLECTION WHICH HASN'T BEEN
TRADITIONALLY THE IDEA APPROACH.
I KNOW THE SENTINEL SURVEILLANCE
PROGRAM WILL ADD ON A T.B.
COMPONENT AND HAS NCB COMPONENT
FOR ITS WORK BUT I JUST WONDER
IF THERE'LL BE SCOPE FOR ADDING
A BIO REPOSITORY ASPECT TO
REQUIRE SIGNIFICANT RESOURCES
BUT WOULD GIVE THE OPPORTUNITY
TO COLLECT IN A WAY WE DON'T
HAVE ANY OTHER RESOURCE.
JUST WONDERING THERE'S AN
APPROACH.
>> WE'VE TALKED ABOUT IT AND
IT'S SOMETHING THAT COMES UP.
OF COURSE, EXACTLY WHAT YOU SAY,
IT'S EXPENSIVE.
THE OTHER IS THE QUALITY OF THE
SPECIMENS YOU KNOW BETTER THAN
ANYONE.
A QUESTION OF HOW THAT CAN BE
DONE IN A COST EFFECTIVE MANNER
IS A TRICKY QUESTION.
IF WE HAD LOTS OF MONEY IT WOULD
BE SOMETHING WE'D CONSIDER BUT
YOU HIT THE NAIL ON THE HEAD.
>> MAYBE NOT COLLECTING FOR THE
SAKE OF COLLECTING BUT IN
APPROACHES TO TARGET HYPOTHESES
TO GET ADDED ON TO ANSWER
BECAUSE I THINK WE KNOW THE
VALUE OF EPIDEMIOLOGICAL DATA
BUT THERE'S MORE WHEN THERE'S
MORE STRATEGICALLY COLLECTED
SAMPLES TO ADD VALUE.
>> I COMPLETELY AGREE AND PARTS
OF THE OBJECTIVE WHERE AT THE
EXPENSE OF REPOSITORIES AND
TRUSTING THE QUALITY OF THE
SAMPLES AND THAT SORT OF THING
IS TOO EXPENSIVE FOR WHAT YOU'RE
TALKING ABOUT, YES.
WE SHOULD HAVE FURTHER
CONVERSATION THAT.
>> GREAT, THANKS, DIANA AND
AMITA FOR THE DISCUSSION.
LET'S MOVE ON TO THE VACCINE
RESEARCH PROGRAM AND MARY
MAROVICH.
>> THANKS SO MUCH, KEN.
YOU THE TRICK.
>> I'M MARY MAROVICH AND GIVING
THE UPDATE ON THE VACCINE
RESEARCH PROGRAM TODAY.
I'LL GO THROUGH A FEW QUICK
UPDATES FOR THE COVID-19
RESPONSE AND FOCUS ON THE
CURRENT VACCINE STRATEGY WHERE
WE'RE DOING A LOT OF DISCOVERY
AND DESIGN AND I'LL REVIEW
CONCEPTS IN EARLY TESTING AND
SOME THAT WERE TESTED IN ADVANCE
STUDIES AND LOOK TO THE FUTURE
FOR DIRECTIONS OF VACCINES.
SO THE MISSION IS REALLY
STANFORD FOR THE VACCINE
RESEARCH PROGRAM.
IT'S JUST TO DESIGN A SAFE AND
EFFECTIVE HIV VACCINE TO HELP US
GET CONTROL OF THE EPIDEMIC AND
THE WAY WE DO THAT IS WE HAVE
THREE DIFFERENT BRANCHES YOU CAN
SEE ON THE BOTTOM OF THE SLIDE
FROM SOUP TO NUTS THE PRECLINIC
AND DEVELOPMENT BRANCH ON THE
LEFT NEXT THE PROMISING VACCINE
BRANCH MOVING THEM TO CLINIC AND
THE MOST PROMISING AND
MANUFACTURABLE AND STABLE IMMUNO
IMMUNOGENS WOULD BE MOVED TO THE
VACCINE CLINICAL RESEARCH
BRANCH.
WITH WE HAVE TALENTED STAFF WHO
SUPPORT ALL THESE BRANCHES AND
WORK TOGETHER AS A MENTIONED TO
ADDRESS THE HIV EPIDEMIC BY
PROMOTING RESEARCH PROGRAMS THAT
DISCOVER NOVEL VACCINE
CANDIDATES AND NEW STRATEGIES
AND CREATIVE STRATEGIES AND USE
THE SUSTAIN COMMITMENT AND
INVESTMENT FROM NIAID TO SUPPORT
THE INVESTIGATORS TO MOVE THE
FIELD FORWARD.
WE USE BOTH SCIENCE AND DATABASE
DECISIONS ALONG WITH PEER REVIEW
AND THEN SOME MILESTONE APPROACH
FOR RESEARCH PERFORMANCE AND
PRACTICE.
THIS IS ALL THE PEOPLE WHO MAKE
THIS HAPPEN IN CASE I RAN OUT OF
TIME.
FIRST TO ACKNOWLEDGE THE
COMMUNITY PARTNERS AND
PARTICIPANTS WITHOUT WHICH WE
COULD NOT MAKE HEADWAY SO THANKS
TO THEM AND FOR SENIOR
MANAGEMENT WITHIN NIAID,
DR. FAUCI AND DR. DIEFFENBACH
WHO CONTINUE TO SUPPORT THE
PROGRAM THROUGH THE UPS AND
DOWNS AND JIM LANE THE DEPUTY
DIRECTOR OF MY OFFICE WHO HAS
DONIO
DONI
DONE YAOMAN'S WORK AND THE
BRANCH CHIEF AND OTHERS IN
PARTICULAR AND ANGELA AND JULIA
HUTTER, AND THOSE WHO
CONTRIBUTED TO THIS PRESENTATION
AND WERE ABLE TO PULL DATA AND
REVIEW IT AND TAKE ALL
RESPONSIBILITY IF ANYTHING'S
UNCLEAR.
I ALSO WANTED TO RECOGNIZE THE
PRINCIPLE INVESTIGATOR LAB SITES
AND USUAL PARTNERS WHO WORK HARD
TO CONTINUE AND I THINK IT WAS
KEN WHO MENTIONED NOBODY'S
REALLY IN THIS FOR THE SHORT
TERM.
IT'S SORT OF A LONG-TERM
COMMITMENT.
CAROL HAS MENTIONED SOME OF
THESE THE ADVANCES WITHIN THE
COVID VACCINE FIELD.
I WANT TO MAKE A POINT I CANNOT
OVER EMPHASIZE THE CONTRIBUTION
THAT THE HIV/AIDS FIELD HAS MADE
TO THE SUCCESSES WITHIN THE
COVID PARTICULARLY VACCINE
WORLD.
WE KNOW THESE WERE REMARKABLE
VACCINATIONS TO COME UP WITH A
VACCINE WITHIN A YEAR AND
DEPLOYED BUT WE KNOW THERE WERE
SUCCESSES BORROWED AND
INVESTIGATORS IN CLINICAL TRIAL
SITES BORROWED FROM THE HIV
FIELD AND A CALL OUT OR SHOUT
OUT.
WE USED THE mRNA PLATFORM FOR
EXPEDIENCY AND THOSE ARE THE
VACCINE CAME OUT FIRST AND
MODERNA WAS JUST ISSUED ITS
BIOLOGICAL LICENSE TODAY FROM
THE FDA, MANY ARE PROBABLY AWARE
OF THAT, AND NOW BOTH mRNA s ARE
FULLY LICENSED PRODUCTS.
THE FACTOR AD VECTOR HAD
STABILITY AND ALL THE VACCINES
HAVE DEMONSTRATED REMARKABLE
EFFICACY AND CLEARLY EXCEED THE
NON-INFERIORITY MARGINS GREATER
THAN 50% ACCURACY AND ALL THESE
HAVE MET THAT MARK WITH THE
EXCEPTION OF SANOFI WHICH WE
EXPECT TO HAVE SOON.
THE INTERESTING FEATURE IS THERE
WAS A NICE SUMMARY ON THE
STRUCTURE OF ENVELOPE SPIKES AND
PRE FUSION AND STABILIZATION,
ETCETERA AND CREDIT TO THE VRC
BECAUSE ALL YOU'LL SEE IN THE
WHOLE SCREEN OF VACCINES, FIVE
OF THE SIX USE THE STABILIZED
S2P THE ONLY VACCINE THAT DID
NOT USE THAT STABILIZED SPIKE
WAS THE GEN OX THEY USED THE
WILD TYPE AND ANYONE WHO WORKS
IN THE VACCINE FIELD KNOW WE TRY
TO DEVELOP TRIMERIC ENZYMES AND
THAT'S TRUE BECAUSE THE NOVA VAX
AND SANOFI PRODUCTS WERE THE
MOST DIFFICULT TO MAKE AND THOSE
ARE IN THE LATER STAGES OF
STUDYING AND APPROVAL THOUGH
NOVAVAX WILL BE SUBMITTING THEIR
UEA SHORTLY IF THEY HAVEN'T
ALREADY AND DEMONSTRATED
EFFICACY.
THANKS TO ALL THE NETWORK FOLKS
AND ALL THE NIH AND OTHERS WHO
HAVE WORKED ON THESE STUDIES TO
THEIR GREAT SUCCESS.
MULTIPLE STUDIES WERE INVOLVED
AND FROM THE PREVENTION
STANDPOINT THE LILLY
CONVERSATION WAS STUDIED AND
DEMONSTRATED GOOD EFFICACY AND
REGENERON STUDY WAS A HOUSEHOLD
STUDY AND THIS WAS CLASSIC HIV
AND SAME WITH ASTRAZENECA THE
ONE IN COMBINATION WITH PREB AND
VIR CAN HANDLE THE ISSUE FOR
TREATMENT AND BEING FROM THE HIV
VACCINE FIELD I THINK WE HAVE
SOME CAUTION TO FIGURE ABOUT
USING A MONOCLONAL ANTIBODY IN
THAT SETTING AND PROTECTING THE
USE OF THAT ANTIBODY AND CURRENT
SHORT SUPPLY.
WE HAVE A LOT OF WORK TO DO
THERE AND AGAIN I'LL THANK ALL
THE NETWORKS FOR THEIR
CONTRIBUTION.
SO AS I MENTIONED, THE SUCCESS
OF THE COVID-19 VACCINES WERE
REALLY A MEDICAL TRIUMPH.
AND A LOT OF HIV INVESTIGATORS
CONTRIBUTED TO THAT.
SO WE HELD A WORKSHOP AT THE END
OF OCTOBER.
WE'RE WANTING TO LOOK BACK OFTEN
THE LESSONS LEARNED ARE WE
LEVERAGED THE HIV VACCINE
ENTERPRISE TO CONTRIBUTE TO THE
COVID VACCINE DEVELOPMENT AND
WHAT CAN WE MOVE FORWARD WITH.
YOU'LL REMEMBER IT WAS A
U.S. GOVERNMENT INTERAGENCY
COLLABORATION WITH PUBLIC
PRIVATE PARTNERSHIPS AND SOME
THING THE VACCINE CONTRIBUTED
WAS THAT WE KNEW WE HAD TO BUILD
TRUST AND TRANSPARENCY FROM
WORKING ALL OF OUR EXPERIENCE IN
WORKING WITH COMMUNITIES HEAVILY
IMPACTED AND THOSE HARD TO REACH
AND KNEW THE POWER OF INCLUSION
AND EMPHASIZED THAT AND BEING
COGNIZANT INCLUSION CREATES
DIVERSITY OF THOUGHT AND
INCREASE PARTNERSHIPS AND LEVELS
THE PLAYING FIELD IN TERMS OF
POWER SHARING AND INFORMS
DECISION MAKING WAS A MAJOR
CONTRIBUTION THAT WASN'T
HARDCORE STRUCTURAL SCIENCE BUT
A CONTRIBUTION FROM THE HIV
FIELD AND THE SPILL OVER EFFECT
WITH THE INVESTMENT IN BASIC
SCIENCE STRUCTURE AND VACCINE
DESIGN AND VALIDATE NEW ASSAYS
AND ONE WAS ADAPTED FOR SARS 2
AND USED FOR STUDIES AND WE KNOW
DATA SHARING AND TRANSPARENCY IS
CRITICAL BECAUSE THE CONSEQUENCE
WAS PROVIDED THEN ALL THE
VACATIONS COULD BE DEVELOPED AND
THE LAST THING TO DRAW THE
PARALLEL IS THE IDENTIFICATION
OF CORRELATES OF PROTECTION WE
NOW HAVE A SUITE OF VACCINES AND
HAVING PROTECTION ALLOWS VACCINE
DEVELOPMENT WITHOUT HAVING TO DO
LARGE SCALE PHASE 3 EFFICACY
TRIALS AND COULDN'T DO PLACEBO
CONTROLLED TRIALS AT THIS POINT.
IT'S TIME CONSUMING AND WE NEED
TO BE ABLE TO MOVE QUICKER AND
WHERE HIV DEVELOPMENT IS BUMPING
UP AGAINST, WE NOW HAVE POWERFUL
PREVENTION METHODS THAT DOING
OUR LARGE-SCALE HIV VACCINE
TRAILS NEED TO BE RECONSIDERED
IN HOW TO ADDRESS THAT AND IF WE
CAN HAVE CORRELATES THAT CAN
HELP INFORM.
I WANTED TO BRING YOU TO THAT
AND JUST LET YOU KNOW THAT THAT
WAS A GREAT WORKSHOP AND
SUPPORTED BY BOTH SIDES.
THE TOP HALF IS THE EMPIRICAL
APPROACH.
THE TWO-PRONGED APPROACH FOR
VACCINE STRATEGIES AND YOU'LL
REMEMBER THAT'S THE RV144 TRYING
TO BUILD AND REPRODUCE OFF THE
FINDING OF VE OF 31% AND THE
IDEA WAS TO MOVE TO AREAS THAT
WERE HARD HIT LIKE SOUTH AFRICA
AND THERE WAS A PROTEIN BOOST
AND UNFORTUNATELY A STUDY WAS
STOPPED FOR EFFICACY TWO YEARS
AGO.
AND SUBSEQUENT WE HAD THE
COLLABORATION USING THE AD
VECTOR BOOSTED WITH AN ENVELOPE
A 705 STUDY IN ADVERSE WOMEN IN
SOUTH AFRICA IN ADDITION THAT
WAS STOPPED FOR NON-EFFICACY
LAST YEAR.
AND CARL MENTIONED WE HAVE A
SISTER STUDY 706 CONTINUING WITH
THE MOSAIC BECAUSE IT HAS AN
ADDITIONAL BOOST.
IT HAS THE ADENOVIRUS AND THEN
GP140 MOSAIC BOOST SO THAT STUDY
IS BEING MONITORED AND KEEP YOU
UPDATED HOW IT'S PROGRESSING BUT
FOR TODAY I THOUGHT WE SHOULD
FOCUS ON THE THEORETICAL
APPROACH AND THE BROADLY
NEUTRALIZING ANTIBODY EFFORTS
ONGOING WHICH ARE REMARKABLE.
THE IDEA IS WE WOULD DEVELOP
VACCINES THAT COULD INDUCE
NEUTRALIZING ANTIBODIES AND USE
BROADLY NEUTRALIZING ANTIBODIES
IN A CONCEPT TO SEE IF IN FACT
NEUTRALIZING ANTIBODIES COULD BE
PART OF THE AMP STUDY AND THE
RESULTS CAME OUT LAST YEAR I'LL
REVIEW IN A SECOND.
IDEALLY, WE'D LIKE TO RECRUIT
ALL THE IMMUNOLOGIC DEFENSES AND
ADAPTIVE HUMORAL AND CELLULAR
AND TODAY I'LL FOCUS ON THE
ELICITATION OF BROADLY
NEUTRALIZING ANTIBODIES FOR
SIMPLICITY.
LET'S TALK ABOUT HOW WE'LL
NEUTRALIZE THESE FOR VACCINE.
YOU SEE THE SPIKES, ETCETERA.
WHAT'S IMPORTANT FOR VACCINE
DEVELOPMENT AS YOU KNOW YOU HAVE
TO HAVE VACCINE TARGETS.
WE HAVE MULTIPLE VACCINE TARGETS
SUSCEPTIBLE TO NEUTRALIZATION.
THERE'S MANY EXPERTS LEADING
THIS FIELD SO WE KNOW HOW TO DO
THAT.
WE HAVE HIGHER FIDELITY IN
ANIMAL MODEL AND PLATFORMS TO
ACCELERATE AND WE KNOW mRNA IS
FASTER THAN TRIMERIC PROTEINS
AND HAVE NEAT DATA BEING
CREATIVE AS FAR AS IMMUNIZATION
STRATEGIES AND INTERVALS AND
USING NANO PARTICLES.
THOSE ARE ALL THE KEY
INGREDIENTS WE THINK ARE NEED.
WE SEE THE IMMUNOGEN DESIGN AND
YOU TAKE THE SPIKES AND DESIGN
YOUR HIV ENVELOPE TRIMER AND
THEN PRIME THE IMMUNE SYSTEM
WITH THAT IMMUNOGEN AND AN
EXAMPLE WOULD BE THE ENGINEERED
GTA WHICH WAS DESIGNED BY
COLLEAGUES AT THE SCRIPPS AND
THAT STUDY I'LL REVIEW BECAUSE
THEY'VE DEMONSTRATED THEY CAN DO
GERM-LINE TARGETING.
THEY CAN STIMULATE THE B CELLS.
WE HIT THE NEXT SLIDE IT WILL
SHOW THE PRECURSOR.
SO THE IDEA IS YOU PROVIDE THIS
TO THE CELLS AND WOULD WANT TO
TRIGGER AS BROADLY AS YOU COULD
THESE PRECURSOR CELLS AND THEN
MOVING TOWARDS THE CENTER THERE
YOU WOULD HAVE TO TAKE THEM TO
BOOT CAMP THE IDEA OF BRINGING
THEM TO THE GYM AND WOULD HAVE
TO STAY WITHIN THE GERMAL CENTER
AND UNDER GO ROUNDS OF AFFINITY
MATURATION WHICH WE NOW
UNDERSTAND HOW WE AFFECT THAT
AND STILL NEED TO UNDER GO
MUTATION AND THROUGH BOOSTING
WE'RE GROWING IN CONFIDENCE WE
CAN END UP WITH MATURE B CELLS
TO PRODUCE BROADLY NEUTRALIZING
ANTIBODIES.
SO THIS IS A BIG ADVANCE IN THE
AANIMAL -- ANIMAL MODEL WHERE
THEY TAKE ADVANTAGE OF THE
CRISPR TECHNOLOGY AND ABLE TO
CUSTOMIZE HUMANIZED B CELL
RECEPTOR EXPRESSING THE
PRECURSORS.
THEY CAN DO THIS WITHIN WEEKS
AND HAVE MICE WITH FUNCTIONAL B
CELL RECEPTOR AND TEST
IMMUNOGENS AND THIS CAN HELP US
RAPIDLY AND ITERATIVELY OPTIMIZE
THE VACCINES BECAUSE WE CAN TEST
THEM IN THE MICE DEVELOPED
QUICKLY AND THEN CAN GO BACK AND
MODIFY THE IMMUNOGEN AND PUT IT
BACK IN MICE.
THIS WAS A HUGE ADVANCE TO --
THESE TYPES OF THINGS WERE
TAKING YEARS TO DEVELOP.
TO DO THAT IN A ONE-STOP THING
OVER WEEKS IS FANTASTIC.
HERE'S THE PRIMATE MODEL HOW THE
HIV AND SHIV BOTH CO-EVOLVE
WITHIN PRIMATES OR HUMANS AND
THE ONLY TWO SYSTEMS WHERE
BROADLY NEUTRALIZING ANTIBODIES
AND WE KNOW THE BODY CAN THEY
CAN THEM AND WE SEE NON-HUMAN
PRIMATES DO AND WHAT'S
INTERESTING IS WHEN THERE'S THIS
ANTIBODY ENVELOPE CO-EVOLUTION
THAT HAPPENS THAT CAN INFORM THE
IMMEDIATE IMMUNOGEN TO DRIVE
THEM TO SUPPORT THE BROADLY
NEUTRALIZING ANTIBODIES.
THIS NON-HUMAN PRIMATE MODEL IS
TO GUIDE THE PRECURSOR B CELLS
THROUGH MATURATION AND THIS
MODEL AS WELL CAN HELP INFORM
VACCINE DESIGN.
IT'S BEEN USED TO GUIDE V3s AND
VARIOUS TYPES OF BROADLY
NEUTRALIZING ANTIBODIES.
THIS IS INTEREST THE CHURCHILL
LAB.
THE G001 STUDY IS THE ENGINEERED
GERM LINE TARGETING A NANO
PARTICLE AND HAS A STRONG
ADJUVANT AND THIS WAS THE FIRST
IN HUMAN STUDY TRY AND PRIME
DIVERSE BROADLY NEUTRALIZING
ANTIBODIES PRECURSORS.
THE STUDY STARTED SEVERAL YEARS
AGO AND THE RESULTS WERE
PROMISING.
BASICALLY SO THE THEY PROVIDED
THIS TWO DIFFERENT DOSES TO 48
PARTICIPANTS AND FOUND IT WAS
WELL TOLERATED AND FOUND IN 97%
OF THE PARTICIPANTS THEY
DEVELOPED THE POSITIVE B CELLS
AT A HIGH ENOUGH FREQUENCY THEY
COULD CONSIDER BOOSTING THOSE
WITH THE RIGHT BOOST.
THIS IS WHERE OUR ANIMALHOLDSS --
ANIMAL MODELS WE LOOKED AT OVER
TIME OR 16 WEEKS WHERE THEY
CHECKED AND ON WEEK 4 THE KD IS
80 AND AS YOU MOVE DOWN TO WEEK
NINE IT'S 14 AND DOWN TO 4.5.
THE VACCINE, THIS HAS INDUCED
THIS MONOCLONAL ANTIBODIES
CONTINUING TO BIND WITH AFFINITY
AND THIS IS THE ANIMAL MODEL
COMING THROUGH IN HUMANS.
SO HOW ELSE?
I TALKED ABOUT THE OTHER
INGREDIENTS TWEAKING THE
ADJUVANT.
THERE'S AN INTERESTING ADJUVANT
COMING OUT OF THE IRVINE
LABORATORY A SELF ASSEMBLY WITH
THE AGONIST NPLA AND DOES
SELF-ASSEMBLE INTO NANO
PARTICLES.
IT'S LIKE WHAT'S BEING USED IN
THE NOVAVAX VACCINE.
IT'S ALMOST LIKE A CAGE YOU CAN
SEE AT THE TOP OF THE SLIDE.
THIS ADJUVANT IS SUPERIOR
ANTIBODIES AND NON-GERMAL
RESPONSES AND MECHANISTICALLY
THE INVESTIGATORS HAVE SHOWN
THAT THE SNP ADJUVANT HAS A MASS
CELL DEPENDENT MANNER AND
INCREASES ANTIGEN DELIVERY.
THIS IS IN MANUFACTURING AND IF
WE GO TO THE NEXT SLIDE I'D LIKE
TO SHOW YOU SOME DATA USING THE
ADJUVANT IN NON-HUMAN PRIMATE
AND ANOTHER BUSY SLIDE.
USING THIS WITH AN ENVELOPE
PRIMER AND IN COLLABORATION WITH
OTHERS THEY DEVELOPED THIS
PRIMING IMMUNIZATION EVERY OTHER
DAY THEY DOSED THE ANIMALS.
IN THAT LONG PRIMING PERIOD IT
LED TO LONG- LIVED GERMINAL
CENTERS FOR MONTHS AND THAT'S
THE ENGINE FOR ANTIBODY
RESPONSES AND TO KEEP THAT
ACTIVITY ONGOING IN THE
PROLIFERATION AND THE AFFINITY
MATURATION IMPROVED THE MAG
MAGNITUDE AND COMPARING TWO
GROUPS.
GROUP GOT THE SEQUENTIAL
IMMUNIZATION OVER 12 DAYS AND A
BOOST AT 10 WEEKS VERSUS GROUP 3
WHO HAD A SIMILAR SLOW 12 DAY
IMMUNIZATION AND WERE BOOSTED
OUT HERE AT WEEK 30 THEN THEY
LOOKED AT THE GERMAL CENTERS AND
ANTIBODIES DEVELOPED AND THE
TYPE OF RESPONSES AND WHAT WE
CAN SAY IS THERE WERE MULTIPLE B
CELL OR LINEAGES IDENTIFIED.
THE TIER 2 NEUTRALIZATION HAS
BEEN THE BEST SO FAR.
THE VIRUSES BEING NEUTRALIZED
AND THE BETTER MEMORY CELLS
THAT'D PROPENSITY TO RECOGNIZE
NON-IMMUNODOMINANT EPITOPE.
WE'RE NOT INTERESTED IN DOMINANT
EPITOPES AT THE BASE WHICH ARE
DISTRACTING.
WE WANT TO EXPAND IT.
YOU CAN SEE HERE IN GROUP 3 AND
GROUP 2, FOR EXAMPLE, THEY HAVE
A MULTITUDE OF RESPONSES
COMPARED TO GROUP 1 WHICH WAS
NOT USING THE SNP ADJUVANT.
CHECKING A LOT OF BOXES THERE
WE'RE ENCOURAGED BY THAT.
NOW WE'VE MOVED BACK INTO
HUMANS.
THIS IS AN ADJUVANT COMPARISON
STUDY WHERE WE'RE LOOKING AT
MULTIPLE ADJUVANTS USING THE
SAME IMMUNOGEN WHICH IS A
STABILIZED TRIMER.
THIS STUDY OPENED A COUPLE YEARS
AGO.
IT HAD BEEN RUN INTO SOME SLOW
DOWNS WITH THE PANDEMIC BUT
BASICALLY PART A IS WHERE THEY
WERE DOING AN ESCALATION AND
SELECT THE HIGHER DOSE OF 5
MICROGRAMS AND FOUND INTERESTING
IMMUNE RESPONSES THAT MAY LEAD
TO A BROADER IMMUNE RESPONSE WAS
THAT ONE COMPARED TO OTHERS.
THE STUDY IS COMPLETELY ENROLLED
AND THEY'RE COMPLETING THESE AND
WE HAVE A PARALLEL PRIMATE STUDY
TO MATCH THE STUDY TO AGAIN
BEGIN TO GET MODELS LINED UP
WITH HUMANS TO GET MORE
INFORMATION AND TRY TO
ACCELERATE THE DEVELOPMENT
PROCESS.
THIS IS JUST A SUMMARY SLIDE
DALE IRVINE PRESENTED AND TIES
IN THE IDEAS I'VE BEEN BRINGING
TO YOU AS FAR AS ADJUVANTS,
IMMUNIZATION REGIMENTS,
FOLICULAR GERMAL CENTERS AND THE
ACTIVITIES BEING DONE IN THE
TRANSLATIONAL BRANCH WHERE THEY
TAKE THE IMMUNOGENS THAT LOOK
PROMISING IN THE PRE-CLINICAL
BRANCH AND ARE MANUFACTURING
THEM EITHER THROUGH CONTRACT
RESEARCH ORGANIZATION
MANUFACTURINGS OR THROUGH SOME
OF OUR OTHER FUNDED
INVESTIGATIVE SITES.
YOU CAN SEE NANO PARTICLES ARE
LISTED HERE VERY IMMUNOGENIC AND
MULTIPLE mRNA PROJECT WE'VE
BEEN FUNDING FOR A LONG TIME NOW
BEING ABLE TO BE TESTED AND ONE
OF THEM I'LL DRAW YOUR ATTENTION
TO WAS THIS MV39 THE TRIMER.
THIS IS THREE DIFFERENT VERSIONS
OF THE MD39 I BELIEVE THE STUDY
IS STARTING AND OPEN I THINK IN
LATE DECEMBER 302.
THE HIV mRNA STUDY LAUNCHED IN
PARALLEL IN ADVANCED FROM THE
PRIMATE MODEL I JUST PRESENTED.
HERE'S WHERE WE ARE TRYING TO
HIGHLIGHT ADJUVANT.
WE KNOW THERE'S ACCESS TO
ADJUVANTS AND WORKED WITH THE
DIVISION AND WE HAVE BEEN ABLE
TO ACQUIRE AND PRODUCE MANY
ADJUVANTS ON THE TABLE AND A
NEWLY COMPENDIUM THE LINK IS
HERE FOR YOU.
THAT'S RUN BUT WE'RE
COLLABORATING WITH THEM AS WELL
AND TO SHOW YOU THE ACTIVITIES
ARE HAPPENING TO MAKE SURE WE
HAVE THE CLINICAL RE-AGENTS FOR
OUR INVESTIGATE ERS .
AND HERE'S WHERE WE'RE AND WE
NEEDED TO TEST VARIOUS VACCINE
CONCEPTS SO I WANT TO GO TO THE
NEXT SLIDE TO REMIND YOU ABOUT
THE AMP STUDY.
SO THE AMP STUDY I WANTED TO
MAKE YOU AWARE IF THE VIRUS WAS
SUSCEPTIBLE AND THE HIGHLIGHT IS
IN RED, IF THE VIRUS WAS
SUSCEPTIBLE TO VRC01 THE
PREVENTIVE EFFICACY WAS 75% WITH
FW THE VIRUS WAS NOT SENSITIVE
VRC01 WAS NOT ABLE TO PREVENT
ACQUISITION.
THIS WAS A REAL ADVANCE.
WE KNOW WE CAN USE ANTIBODIES IN
VIVO.
AND THIS IS WHERE SOME OF OUR
NEXT STEPS ARE COMING WHERE
WE'LL SEE IF WE CAN PREVENT HIV
INFECTION WITH A TIGHTER
ANTIBODY.
AND FUTURE DIRECTIONS, I'LL SUM
UP.
THIS IS FOR YOUR INFORMATION.
I WON'T REVIEW ALL THIS BUT GIVE
YOU INFORMATION STUDIES BEING
DONE WITH THE ANTIBODIES MARKED
IN BLUE WITH THE mRNA s AND THIS
IS THE CHIP COLLABORATIVE
IMMUNOGEN PROJECT WHERE WE HAVE
TO WORK TOGETHER TO PRIORITIZE
WHICH ENVELOPE IMMUNIMMUNOGENS AND
THIS IS FOR YOUR INFORMATION AND
SHOULD BE INCLUDED IN YOUR BOOK
OR SLIDE DECK AND WOULD HELP US
SHEPHERD THE BROADLY
NEUTRALIZING RESPONSE AND SOME
OF THE TRIMERS USED ONCE PRIMED.
THESE ARE THE PROTOCOLS IN THE
PIPELINE FOR YOUR INFORMATION.
SO THANK YOU FOR ANY ADDITIONAL
TIME YOU GAVE ME THERE, KEN.
WE THINK THE FIELD VACCINE
DEVELOPMENT IS BRIGHT AND WE'RE
ACKNOWLEDGING THE COMMUNITY AND
PUBLIC PRIVATE PARTNERSHIPS AND
TRYING TO TAKE ADVANTAGE OF ALL
THE ADVANCES.
>> SO MUCH SCIENCE AND EXCITING
AND WE'RE A MINUTE BEHIND BUT
WE'LL TAKE A COUPLE MINUTES FOR
QUESTION AND I THINK WE'LL CATCH
UP AFTERWARDS.
QUESTIONS FOR MARY ABOUT THE
VACCINE PROGRAM?
>> IS THERE ANY INDICATION OF
WHICH ANIMAL MODEL FOR THE
HUMANS THAT DEVELOP THE BROAD
NEUTR
NEUTRALIZ
NEUTRALIZERS?
>> THE MOUSE MODELS CAN BE
CUSTOMIZED AND WE THINK THE
MOUSE MODEL THOUGH FOR THOSE OF
US HAVE BEEN IN THE FIELD THE
MOUSE MODEL HASN'T BEEN FAVORED
BUT IT'S SO MUCH FASTER WITH THE
GENETIC TECHNOLOGY.
SOME GROUPS ALMOST EXCLUSIVELY
USE THE MOUSE MODEL.
WE LIKE THE PRIMATE MODEL FOR
OTHER ATTRIBUTES AND CHALLENGE
THE FACT THEY DO GENERATE
BROADLY NEUTRALIZING ANTIBODIES,
AGAIN, IT'S A SMALL PERCENTAGE
OF ANIMALS BUT I THINK THE MOUSE
MODEL WOULD BE THE BIGGEST
ADVANCE IF I WERE TO ANSWER THAT
QUESTION.
>> THANK YOU.
I THINK THE HUMANIZATION OF THE
MODEL IS A PRETTY IMPORTANT STEP
FORWARD.
SOME DIFFERENCES IN THE
ACTIVATION THAT DRIVES THE
ANTIBODY THAT COULD DETERMINE A
REPERTOIRE ALSO.
>> I TOTALLY AGREE WITH YOU.
WE HAVE TO TAKE THAT WITH A
GRAIN OF SALT THIS WHOLE LIKE
THE ONLY LIVE TWO YEARS OR
SOMETHING AND WE'RE TALKING
ABOUT COMPRESSING ALL THAT.
IT'S SO EXCITING THOUGH THAT
SOME OF THE THINGS THAT WE'VE
SEEN IN THE MOUSE MODEL HAS
BEGUN TO COME FORWARD IN HUMANS.
A LOT OF THAT WILL NOT BE
IDENTICAL.
>> A LAST QUESTION FROM KEITH
AND THEN A BREAK.
>> SURE.
I ENJOYED THE SLIDE ABOUT THE
VALUE AND THE WORKSHOP ABOUT THE
VALUE OF THE HIV EFFORTS TOWARDS
THE COVID VACCINE AND HAD A
BULLET ABOUT OF THIS KIND OF
WORKING IN REVERSE AND BEING
INVOLVED WITH A HYBRID PROGRAM
AND A TREMENDOUS NGS AND ROBOTIC
ROBOTICS AND SO FORTH WE'RE
THINKING ABOUT WHAT HAPPENS WHEN
WE GET TO THE PROMISED LAND
COVID IS MAYBE NOT THE ABSOLUTE
OVERWHELMING EMERGENCY AND HOW
TO LEVERAGE THAT.
I'M WONDERING IF YOU CAN EXPAND
ON WHETHER THERE'S FORMAL
EFFORTS TO THINK OF LEVERAGING
THIS HUGE INVESTMENT MADE OVER
THE PAST TWO YEARS FOR THINGS
LIKE HIV AND LONGER TERM
PROBLEMS.
>> OH, YEAH.
I PROBABLY WOULDN'T BE THE
WORLD'S BEST EXPERT BUT IF I CAN
MAKE ONE COMMENT SAY FOR EXAMPLE
REGARDING THE AMP STUDY, WE
OVEREST MATE THE CIRCULATING
STRAINS -- OVER ESTIMATED THE
CIRCULATING STRAINS AND COULD BE
PROBABLY BETTER INFORMED WITH
THE EVOLUTION OF THE HIV
EPIDEMIC WHICH HAS CHANGED GIVEN
THE TYPE OF VIRUS AND THE OTHER
CONDITIONS THE ONGOING EPIDEMIC
FOLKS ARE FACING AND WOULD BE
WELL SUITED FOR THE RESEARCH IN
GENER
GENERAL.
WE'LL TAKE A BREAK.
>> HOW ABOUT WE TAKE AN EIGHT
MINUTE BREAK.
AND WE HAVE FOUR MORE GROUPS SO
TAKE A BREAK STRETCH YOUR LEGS
AND WE'LL BE BACK.
WELCOME BACK, EVERYONE.
DOESN'T LOOK LIKE WE LOST TOO
MANY PEOPLE, IF ANYONE AT ALL.
AND SO I WAS PROMISED WE'D PICK
UP A MINUTE OR SO PER PROGRAM SO
WE'LL END ON TIME.
LET ME HAND IT OVER TO PETER KIM
OF THE THERAPEUTICS RESEARCH
PROGRAM.
WE LOOK FORWARD TO HEARING FROM
YOU.
GREAT.
HOPEFULLY EVERYONE CAN SEE ME
AND SO GOOD AFTERNOON EVERYONE.
IT'S A PLEASURE TO BE HERE TODAY
AND TO PRESENT TO YOU SOME OF
THE RECENT ADVANCES AND UPDATES
TO THE THERAPEUTIC RESEARCH
PROGRAM.
IT LOOKS LIKE I DON'T HAVE
CONTROL.
>> THERE WASN'T A NEED TO GO
THAT FAST, PETER.
>> A CUMULATED ALL THE KEY
STROKES AND DID IT ALL AT ONCE.
THERE'S A LAG.
RYAN, MAYBE YOU CAN TAKE CONTROL
AND ADVANCE FOR ME.
IT IS NOT ADVANCING AT ALL,
PETER?
DOES IT ADVANCE ON YOUR END OR
IS IT STUCK?
OKAY.
SO JUST TO START AGAIN.
SO I'D LIKE TO JUST THANK FIRST
OF ALL BEFORE I HEAD INTO THE
PRESENTATION THE MANY MEMBERS OF
THE THERAPEUTIC RESEARCH
PROGRAM.
I'M SIMPLY HERE ON THEIR BEHALF
AND THE WORK I'M ABOUT TO
PRESENT IS MADE POSSIBLE BECAUSE
OF THEIR WORK AND EFFORTS THEY
HAVE PUT INTO THE PROGRAM IN
ADMINISTRATING THE GRANTS AND
CONTRACTS WE OVERSEE IN THE PAST
YEAR.
I WILL SAY THAT BEING ON A FULL
100% TELEWORK ENVIRONMENT IS NOT
ALWAYS EASY BUT OUR STAFF HAD
REALLY SHOWN A LOT OF RESILIENCE
THIS PAST YEAR AND IT'S BEEN
EXCELLENT TO SEE THAT WE CAN
STILL ADVANCE REALLY CRITICAL
THERAPEUTIC SCIENCE DESPITE THE
CHALLENGES THE COVID-19 PANDEMIC
HAS THROWN OUR WAY.
SO IMPORTANT TRANSITIONS IN TRP.
WE HAD BRANCH CHIEFS RETIRE THIS
YEAR.
T
ONE HAD BEEN INVOLVED WITH THE
DIVISION OF AIDS ON ALMOST SINCE
THE VERY BEGINNING HAD RETIRED
THIS PAST YEAR AND DR. JOE
FITZGIBBON IN THE DRUG
DEVELOPMENT CLINICAL SCIENCES
BRANCH CHIEF RETIRED AFTER 20
YEARS OF SERVICE.
THEY BOTH LEAVE IMPORTANT
LEGACIES IN TRP AND OVERALL IN
THE DIVISION AND THEY'LL BE
SORELY MISSED.
AND ONE NEW ANNOUNCEMENT
PRESENTED DR. FATIMA JONES HAS
TAKEN OVER AS OF DECEMBER OF
LAST YEAR.
I WILL KNOW THAT DR. JONES IS A
WELCOMED ADDITION TO OUR PROGRAM
AS MANY PEOPLE HAVE NOTED.
UNFORTUNATELY, WE DO NOT HAVE A
REPLACEMENT FOR DR. HAGNER IF
PEOPLE KNOW OF SOMEONE LOOKING
TO FIND A CAREER AT THE NIH
REACH OUT TO ME.
THE THERAPEUTIC RESEARCH PROGRAM
HAS IN OPPOSITION TO THE BASIC
VACCINE RESEARCH PROGRAM HAS
SOMEWHAT BROADER AGENDA AND
MISSION.
OUR GOAL IS TO IMPROVE THE
HEALTH OF PEOPLE LIVING WITH HIV
BY DEVELOPING NEW AND IMPROVING
THERAPEUTICS AND DIAGNOSTICS IN
ASSOCIATED STRATEGIES TO ACHIEVE
VIRAL SUPPRESSION AND REMISSION.
HEALTH OUTCOMES IN PEOPLE LIVING
WITH HIV ARE NOT JUST ASSOCIATED
WITH THE HIV INFECTION ITSELF
AND BASED ON ALSO A NUMBER OF
CO-INFECTIONS AND COMORBIDITIES.
WE ALSO FOCUS ON THOSE DISEASES
TO REALLY MAKE AN OVERALL IMPACT
ON THE HEALTH OF PEOPLE WITH
HIV.
SO THOUGH WE IN TRP HAVE A
FAIRLY BROAD PORTFOLIO OF GRANTS
AND CONTRACTS AND COOPERATIVE
AGREEMENTS THAT ARE BOTH
TRANSLATIONAL AND CLINICAL IN
NATURAL, MOST OF OUR ACTIVITIES
ARE WEIGHTED TOWARDS CLINICAL
TRIALS WITH MORE THAN 80
CLINICAL TRIALS ACTIVE AND/OR IN
DEVELOPMENT.
THE NUMBER IS SLIGHTLY HIGHER
THAN MY PRESENTATIONS FROM
RECENT PAST.
LAST YEAR WE HAD ABOUT 70 IN
DEVELOPMENT AND THE REASON BEING
PARTLY BECAUSE OF THE DELAYS
CAUSED BY THE COVID-19 PANDEMIC
AND PARTLY BECAUSE OF A NEW
SCIENCE WITH IMPORTANT
OPPORTUNITIES IN THE FIELD.
IN 2021 WE HAD 16 FOAs AND SOME
HAD SET ASIDE FUNDING AND SOME
DID NOT FOR THE SAKE OF KEEPING
THIS MOVING FORWARD I WILL NOTE
THAT OUR FOAs AGAIN MATCHING OUR
OVERALL BROAD AGENDA DIVERSIFIED
ACROSS NOT ONLY HIV BUT T.B.,
HEPATITIS AND OTHER FIELD OF
INTEREST.
THE OTHER NOTE I'LL MAKE IS OVER
THE PAST COUPLE YEARS I'VE
NOTICED A TREND TOWARDS
INCREASING COLLABORATION WITH
OTHER PROGRAMS, DIVISIONS AND
I.C.s ACROSS THE NIH WHICH I
THINK IS AN IMPORTANT AND
POSITIVE DEVELOPMENT.
I THINK PART OF THE REASON FOR
THIS IS THAT WE'RE MAKING A
CONSCIOUS EFFORT TOWARDS GREATER
COLLABORATIVE APPROACHES AND
ALSO IT SPEAKS TO THE CHANGING
NATURE OF THE SCIENCE WHERE MANY
PREVIOUSLY DISPARATE AREAS OF
SCIENCE ARE EMERGING IN
ADDRESSING HIV OVERALL.
FROM THIS POINT ON I'LL DELVE
INTO OUR AREAS OF AREAS OF
INTERESTING, HIV, HIV-ASSOCIATED
COMORBIDITITIEY
COMORBIDITITIIES AND T.B. AND
HEPATITIS AND TO DEVELOP HOME
BASED CARE AND POINT-OF-CARE
HOME-BASED DIAGNOSTICS AND
REMISSION AND CURE AND ADDRESS
KEY COMORBIDITIES MAINLY THROUGH
COLLABORATIONS AS SAID BEFORE.
THERE SEEMS TO BE A SIGNIFICANT
LAG.
I'LL TRY TO SWITCH DEVICES.
GIVE ME ONE SECOND, PLEASE.
SORRY ABOUT THIS.
>> CAN ANYONE ELSE CONFIRM THE
SLIDES ARE ADVANCING.
I THINK IT'S LAGGING ON HIS END.
>> WE CAN SEE THEM ADVANCING.
ONE RECENT ADVANCE WE WERE ABLE
TO CONTRIBUTE TO IS THE
DISCOVERY AND DEVELOPMENT OF A
NEW FIRST IN CLASS ANTI-HIV
DRUG, STP 0404 AN INHIBITOR AND
THEY WERE ABLE TO BOTH DISCOVER
THIS NEW DRUG WHICH IS A
NON-CATALYTIC BINDER TOE THE
INTEGRASE INHIBITION SITE IN HIV
AND ALSO IS A HIGHLY POTENT NEW
COMPOUND THAT HAS ALREADY
ENTERED PHASE 1 CLINICAL TESTING
AND ALSO HAS POSSIBILITIES FOR
LONG-ACTING FORMULATION IN
DEVELOPMENT AND I THINK HAS TO
NEW CLASSES OF DRUGS ARE
IMPORTANT TO MAKE SURE WE KEEP
THE FIELD MOVING AND RESISTANT
TO DEVELOPMENT OF RESISTANCE TO
HIV AND I THINK NOW IT'S COMMON
KNOWLEDGE AND COMMONLY ACCEPTED
LONG-ACTING FORMULATIONS CAN
HAVE AN IMPACT ON THE PANDEMIC
OF HIV AND WE'RE GLAD TO BE
SUPPORTING GRANTS LIKE THIS.
IN THE FIELD OF UNDERSTANDING
HIV AND IV CURE WE IDENTIFIED
METABOLIC BIOMARKERS THAT MAY
PREDICT POST-TREATMENT CONTROL
OF HIV.
THIS PARTICULAR EXPERIMENT THE
INVESTIGATORS TOOK SAMPLES OF
HIV FROM A COHORT OF
PARTICIPANTS THAT HAD UNDER GONE
INTERRUPTIONS AND LOOKING AT THE
MRAZ THAT
THEY WERE ABLE TO PREDICT TIME
TO REBOUND WITH 74% CAPACITY AND
ALSO THE PROBABILITY OF OVERALL
VIRAL REMISSION WITH THE 97.5%
CAPACITY.
THIS IS EARLY WORK AND SOME
NEEDS TO TAKE PLACE FOR CLINICAL
UTILITY AND AS PREDICTED
BIOMARKERS AND DESIGN OF OUR
CURE HIV CLINICAL TRIALS.
WE THINK IT'S A PROMISING
ADVANCEMENT AND LOOK FORWARD TO
ADVANCING THIS AREA OF RESEARCH
FURTHER.
WE ALSO WORKED WITH A LAB AND
FOUND HIV HAS THE ABILITY TO
BUILD RECIVILITIAN RESISTANCE AND THEY TOO K
BLOOD SAMPLES AND FOUND THE
VIRUSES THAT SUCCESSFULLY REVAKT
REVAKT -- REACTIVATE ARE
RESISTANT AND DURING ACUTE
INFECTION THERE'S HIGH
RESISTANCE AND AFTER THE FIRST
YEAR WHILE ON TREATMENT THE
RESISTANCE GOES DOWN BUT ONCE
TREATMENT IS TAKEN AWAY AND THE
VIRUSES REBOUND AGAIN THERE'S A
HIGH RATE OF RESISTANCE AMONG
THE VIRUS SHOWING THAT THE HIV
HAS THE ABILITY TO EVOLVE
RESISTANCE AGAINST THE
RESPONSES.
WE HAVE A CLINICAL TRIAL CALLED
THE REPRIEVE STUDY AND THEY TOOK
A SUB COHORT OF PARTICIPANTS
ENROLLED AND PERFORMED C.T.
ANGIOGRAPHY LOOKING FOR PLAQUES
AND THE EXISTENCE OF THE
CORONARY PLAQUE WAS ASSOCIATED
WITH IMMUNE AND INFLAMMATION AND
ACTIVATION MARKERS THOUGH IT WAS
RARE BUT HIGH-RISK PLAQUE WAS
SEEN IN 20% OF THE PARTICIPANTS.
THERE'S A CLINICAL TRIAL TO LOOK
IN PERSONS WITH HIV AND THIS
STUDY WILL COMPARE VIRAL CONTROL
DURING ATI BY STUDY ARMS AND
HISTORICAL CONTROLS IT'S
IMPORTANT TO LOOK AT THE
ANTIBIOTICS WITH OTHER AGENTS TO
SEE WHAT IMPACT THEY HAVE ON THE
RESERVOIR AND POSSIBILITY OF HIV
CURE AND REMISSION.
BEYOND PASSIVE INFUSION OF BROAD
NEUTRALIZING ANTIBODIES WE
BELIEVE THE VACCINES MAY HAVE A
THERAPEUTIC BENEFIT FOR PERSONS
LIVING WITH HIV.
WE'RE FUNDING PHASE 1 CLINICAL
TRIALS TO EVALUATE THIS CONCEPT
LOOKING AT THE SAFETY,
TOLERABILITY AND IMMUNOGENICITY
OF THE ENVELOPE PROTEIN IN HIV
INFECTED ADULTS.
FROM A LARGER PERSPECTIVE WE'RE
ALSO WORKING IN CONJUNCTION WITH
THE ACTG TO DEVELOP A PLATFORM
OR MASTER TRIAL TO TEST MULTIPLE
IMMUNOGEN FOR RESPONSE FOR
PEOPLE LIVING WITH HIV.
PROGRESSING ON THE CASCADE OF
THE CLINICAL TRIAL WITH THE
PRIMARY ON THE OBJECTIVE TO
DIFFERENCES IN THE WEIGHT CHANGE
OVER 48 WEEKS COMPARED TO
REMAINING INHIBITER CONTAINING
REGIMENT.
IT'S LOOKING TO ABOUT 2200
PARTICIPANTS AND THOUGH THE
TRIAL HAS SOME WAYS TO GO IN
TERMS OF FINALIZING ENROLLMENT,
WE THINK THE RESULTS OF THIS
TRIAL WILL SHED IMPORTANT LIGHT
ON CLINICAL STRATEGIES TO
OUTCOMES AND PROTECT
PARTICIPANTS WITH WEIGHT GAIN
ASSOCIATED WITH THE INHIBITERS
AND TRF.
SO BEYOND THIS THOUGH THE TRIALS
I PRESENTED ARE FAIRLY RANGE
FROM PHASE 1 TO PHASE 4 CLINICAL
TRIALS, THERE'S ALSO A NUMBER OF
REALLY IMPORTANT MECHANISTIC
CONCEPTS THAT ARE BEING
DEVELOPED IN THE HIV CURE AND
REMISSION FIELD.
TO SUPPORT THE POSSIBILITY OF
RAPIDLY ADVANCING THESE CONCEPTS
INTO A CLINICAL TRIAL WITHOUT
THE DIFFICULTIES ASSOCIATED WITH
INVESTIGATOR INITIATED GRANTS,
WE'RE PARTNERING WITH THE ACTG
AND THEY STARTED A NEW SMALL
CLINICAL TRIALS UNIT WHEREBY
THEY'LL ACCEPT PROPOSALS AND
APPLICATIONS FOR THE SMALL
CLINICAL TRIALS IN HIV.
THE RFA IS RUN THROUGH THE ACTG
AND THEY'LL ACCEPT APPLICATIONS
TWICE A YEAR AND THOSE ARE
REVIEWED AND FUNDED AND THE
TRIALS IMPLEMENTED MUCH MORE
QUICKLY UTILIZING THE BACKBONE
AND INFRASTRUCTURE OF THE ACTG.
OBVIOUSLY, WE'RE NOT ONLY
INTERESTED IN CURE BY ALSO
ENDING THE HIV EPIDEMIC AS
DISCUSSED BY DR. DIEFFENBACH AND
DR. FINZI AND WE'RE CONTRIBUTING
EFFORT.
WE COLLABORATED WITH NIDA AND
NIMH TO PUT OUT AN APPROACH TO
ENDING THE HIV EPIDEMIC.
THE FOA IS CURRENTLY CLOSED AND
WE'RE EVALUATING OUR
POSSIBILITIES OF FUNDING THE TOP
SCORING APPLICATIONS AS WE
SPEAK.
BEYOND THAT DR. DIEFFENBACH
SHARED DETAILS ABOUT UTILIZING
THE SPIR MECHANISM TO ADVANCE
AND FOSTER THE DEVELOPMENT OF
NOVEL POINT OF CARE ASSAYS
INCLUDING TESTING FOR RESISTANCE
AND DRUG MONITORING AND
PHARMACOLOGIC ADHERENCE.
AS I STATED EARLIER, WE BELIEVE
RESEARCH ON HIV COMORBIDITIES
HAVE A SIGNIFICANT IMPACT ON THE
HEALTH OUTCOMES OF PERSONS WITH
HIV AND WE REALLY WORKED WITH
OTHER I.C.s TO DEVELOP
COLLABORATIONS THAT WOULD IN
BENEFICIAL.
AS YOU CAN SEE WE HAVE A
NATIONAL OF COLLABORATIONS WE
HAVE ADVANCED IN THE PAST AND WE
CONTINUE TO DISCUSS WITH OTHER
I.C.s, INSTITUTES, DIVISIONS AND
OTHER ORGANIZATIONS TO ADVANCE
POSITIVE COLLABORATIONS TOWARDS
THIS EFFORT.
WE THINK THIS IS AN IMPORTANT
WAY OF ADVANCING THE SCIENCE,
NOT ONLY ARE FUNDS LIMITED BUT
THE LEVEL OF EXPERTISE IS
LIMITED AND COUNTING ON THE
EXPERTISE OF OUR COLLEAGUES
ACROSS THE NIH IS IMPORTANT IN
ADVANCING THIS FIELD.
IN THE AREA OF TUBERCULOSIS
WE'RE LOOKING AT NEW DIAGNOSTICS
AND TREATMENTS AND VACCINES
THROUGH CLINICAL AND
OBSERVATIONAL RESEARCH IN OTHER
REGIONS BUT ALSO THROUGH THE
DEVELOPMENT OF FOAs AND RO1s TO
LOOK AT THE PATHOGENESIS OF T.B.
AND HIV.
PEOPLE WITH HIV ARE 15 TO 20
TIMES MORE LIKELY TO FALL ILL
WITH T.B. WITH GREATER FATALITY
RATES AND WHAT'S CONCERNING TO
MANY IN THE FIELD IS THE RATE OF
DRUG RESISTANCE IN T.B. IS
DECREASING AND THAT'S HIGHER IN
THE HIV INFECTED POPULATIONS
ACROSS THE WORLD.
THE T.B. PIPELINE IS THE MOST
ROBUST AND THERE'S A NUMBER OF
AGENTS NOT ONLY THE PRE-CLINICAL
DEVELOPMENT STAGE AND IN PHASE
1, 2 AND 3 CLINICAL DEVELOPMENT.
AND AS THE CLINICIANS KNOW IT'S
NOT A SINGLE TREATMENT, SINGLE
DRUG TYPE TREATMENT BUT SIMILAR
TO HIV AND REQUIRES COMBINATION
APPROACHES.
TWO OF THE MOST PROMISING NEW
DRUGS ON THE MARKET ARE THESE
TWO AND THEY BOTH PROLONG THE
QTC INTERVAL SO IT WAS IMPORTANT
TO IDENTIFY WHETHER THE
COMBINATION OF THESE TWO
TREATMENTS WOULD BE SAFE FOR
PARTICIPANTS TO USE FOR THE
TREATMENT OF T.B.
SO THE ACTG UNDERTOOK CLINICAL
TRIAL TO LOOK AT THE
PROLONGATION IN THIS POPULATION.
FOR THELY THEY FOUND WHILE THERE
IS ADDITIVE QTC PROLONGATION THE
COMBINATION WAS SAFE AND THE
PROLONGATION DID NOT GO BEYOND
FOR THE TREATMENT OF PATIENTS
WITH NORMAL BASELINE QT.
THERE'S POTENTIAL REGIMENTS THAT
CAN BE DEVELOPED WITH DRUGS IN
THE PIPELINE AND WE ARE TESTING
REGIMENTS IN PARALLEL WITH THE
IDEA THAT THOSE REG I AMS WITH
THE GREATEST -- REGIMENTS WITH
THE GREATEST EFFICACY WOULD BE
MOVED TO PHASE 3 CLINICAL
TRIALS.
AND IN THE FIELD OF HEPATITIS,
WE'RE LOOKING FOR NOVEL
TREATMENTS FOR HEPATITIS B CURE
AND VACCINES FOR PERSONS LIVING
WITH HIV.
TREATMENT SIMPLIFICATION FOR
LONG ACTING TREATMENTS FOR
HEPATITIS B AND C AND
DIAGNOSTICS FOR HEPATITIS B AND
C.
I THINK MOST PEOPLE KNOW THAT
T.B. IS THE LEADING CAUSE OF
MORBIDITY AND MORTALITY IN
PERSONS WITH HIV, HEPATITIS B
AND C ARE THE SECOND MOST
IMPORTANT CAUSE OF MORBIDITY AND
MORTALITY IN PERSONS LIVING WITH
HIV WITH MUCH OF THE BURDEN WITH
PERSONS IN SUB-SAHARAN AFRICA.
THERE'S A CLINIC STUDY 5379 TEST
NEW VACCINE AND OBJECTIVES IS TO
COMPARE THE RESPONSE OF A
TWO-DOSE REGIMENT OF THIS VERSUS
THE STANDARD THREE-DOSE REGIMENT
AND PERSONS WITH HIV AND
COMPARING THE THREE-DOSE
REGIMENT VERSUS THE STANDARD
THREE-DOSE REGIMENT IN THE SAME
POPULATION AND LASTLY TO
DETERMINE THE SPIR OF THE
THREE-DOSE REGIMENT IN THE
VACCINE NAIVE PERSONS WITH HIV.
IT'S A PHASE 3/4 STUDY AND
BELIEVE IN WORKING WITH THE
COMPANY THIS TRIAL COULD POSE
IMPORTANT DATA TO IMPROVE
VACCINES OF PERSONS LIVING WITH
HIV.
IN TERMS OF HEPATITIS B CURE WE
BELIEVE THERE'S A LOT OF WORK
THAT NEEDS TO HAPPEN IN THE
CO-INFECTION SPACE AND THE
DEVELOPMENT OF NEW THERAPEUTICS
AND DIAGNOSTICS TO NOT ONLY HELP
OUR CLINICAL TRIAL EFFORTS AND
USED CLINICALLY TO BETTER
IDENTIFY AND TREAT PATIENTS WITH
HPV AND HIV CO-INFECTION.
IN THE SARS COV2 FRONT, OUR
PROGRAM IN COLLABORATION WITH
THE ACTG HAS BEEN HARD AT WORK
DEVELOPING NOVEL TREATMENTS FOR
EARLY COVID-19.
WHAT STARTED OUT AS ONE SINGLE
STUDY CALLED ACTIV 2 HAS GROWN
TO A FAMILY OF STUDIES THAT WE
CALL ACTIV 2X.
THEY GO BY THE NAME ACTIV 2 AND
OTHERS AND WE'VE BEEN SUCCESSFUL
IN A YEAR AND A HALF WE'VE BEEN
ABLE TO EVALUATE OVER 10 AGENTS
IN THE PHASE 2 CATEGORY STUDY
CATEGORY AND THEN ALSO PROGRESS
SOME OF THEM INTO PHASE 3 AS
DR. DIEFFENBACH NOTED, WE HAVE
FINISHED PRELIMINARY EVALUATION
OF THE MONOCLONAL ANTIBODIES
SUBMITTED FOR AN EUA
CONSIDERATION.
WE'RE ACTIVELY ENROLLING INTO A
PHASE 3 OF THE POLY CLONAL
ANTIBODIES AND HAVE SEVERAL
AGENTS AND A PROTEASE INHIBITER
AND A COUPLE OF OTHERS EARLIER
PHASED AGENTS WAITING IN THE
WINGS TO GET STARTED IN PHASE 3
EVALUATION.
WE WERE ABLE TO LOOK AT THIS
PHASE 3 STUDY AND FOUND THE
COMBINATION ANTIBODIES WERE
HIGHLY EFFECTIVE IN REDUCING THE
RISK OF HOSPITALIZATION AND
DEATH WITH A 78% REDUCTION IN
RISK.
WE ALSO FOUND TREATMENT WITHIN
THE FIRST FIVE DAYS SHOWED
SIMILAR EFFICACY EVEN AS
TREATMENT FROM SIX TO 10 DAYS
FROM SYSTEM ONSET WHICH IS WE
BELIEVE A VERY IMPORTANT FINDING
ESPECIALLY GIVEN THE FACT THAT
SOMETIMES A DIAGNOSIS OF
PATIENTS WITH COVID-19 CAN BE
DELAYED DUE TO DIFFICULTY EITHER
FINDING A DIAGNOSTIC TEST OR
GETTING THE RESULTS BACK FROM
THE LAB.
SO I'LL END THERE.
I APOLOGIZE AGAIN FOR THE CHOPPY
PRESENTATION DUE TO THE INTERNET
LAG.
I WOULD LIKE TO ACKNOWLEDGE THE
MANY PEOPLE WHO ARE IN TRP THAT
CONTRIBUTE TO THIS WORK.
THEY'VE DONE A TREMENDOUS JOB IN
NOT ONLY KEEPING THE SCIENCE OF
HIV, T.B. AND HEPATITIS MOVING
FORWARD AND CONTRIBUTING TO THE
OVERALL U.S. GOVERNMENT COVID-19
EFFORTS.
>> THANK YOU FOR THE GREAT
OVERVIEW.
A LOT OF ACTIVITY.
EXCITING ACTIVITY.
MAYBE WE COULD MAKE ONE QUESTION
IF ANYONE HAS A BRIEF QUESTION
FOR PETER.
WE'VE ALL BEEN IMPRESSED WITH
THE ACTIVE STUDIES.
IT'S BEEN FANTASTIC.
THANK YOU.
ALL RIGHT.
WHY DON'T WE MOVE ON TO THE
PREVENTION SCIENCES PROGRAM.
AND LOOK FORWARD TO SHERYL
ZWERSKI'S PRESENTATION.
>> GOOD AFTERNOON.
I'M EXCITED TO PRESENT TO YOU
THE PREVENTION SCIENCES PROGRAM
OVERVIEW AND UPDATE.
WE'LL DO A BIT OF BACKGROUND AND
THEN TALK ABOUT TRANSITIONS AND
CHANGES IN THE PROGRAM SOME
HIGHLIGHTS OF WHAT'S UP NEXT FOR
US, WHAT WE SEE AS SOME OF THE
HIGH LEVEL CHALLENGES AND
OPPORTUNITIES AND THEN OF COURSE
IF TIME PERMITS, QUESTIONS.
EVERYONE IS AWARE OF THIS AND
THOUGHT IT WAS IMPORTANT TO SET
THE STAGE TO REMIND EVERYONE WE
HAVE JUST UNDER 38 MILLION
PEOPLE LIVING WITH HIV, 1.7
MILLION OF THOSE WILL CHILDREN.
AND THEN 1.5 MILLION PEOPLE
NEWLY INFECTED AND 150,000 OF
THOSE ARE CHILDREN UNDER THE AGE
OF 15 YEARS.
ALSO AND NO SURPRISE TO ANYONE
WE CERTAINLY DID NOT ACHIEVE THE
2020 PREVENTION TARGET.
BE A CHALLENGE TO MEET THE 2025
TARGET BUT WE'RE HOPING WITH
SOME OF THE NEW PREPAREER
SOME OF THE NEW PREPARE EER PREVENTION
PROJECTS WE CAN MAKE PROGRESS.
AND TO REMIND EVERYONE OF HOW
PERSON IT IS TO KEEP THINKING
ABOUT KEY POPULATIONS AT RISK
FOR HIV.
AND FOCUSSING AND DEVELOPING
PREVENTIONS AND STRATEGIES FOR
THESE POPULATIONS.
THERE'S KEY CHANGES THAT HAVE
OCCURRED IN THE PAST YEAR.
AND I DID WANT TO POINT OUT
THERE WERE THREE REQUIREMENTS
THAT OCCURRED IN THE PAST YEAR
THAT HAVE MEANT IMPORTANT
CHANGES TO THE PROGRAM.
MOST KNOW THE LONG STANDING
BRANCH CHIEF FOR THE PRECLINICAL
BRANCH AND IN THE LAST COUPLE
YEARS HE HAD SERVED AS THE
ACTING DEPUTY DIRECTOR FOR THE
PROGRAM OVERALL.
HE RETIRED IN 2021 WE HAVE A NEW
DIRECTOR.
JAMES CUMMINS STEPPED IN FOR THE
PRE CLINICAL BRANCH AND WE HAD
DAVID BYRNES RETIRED WHO HAD
BEEN A LONG TIME BRANCH CHIEF
FOR THE CLINICAL PREVENTION
BRANCH AND WE HAVE A BRANCH
CHIEF FOR THE BRANCH AND
DR. TORRES WHO HAS BEEN WORKING
AND CONTINUES TO WORK ON SOME OF
THE MICROBICIDE WORK.
WE ALSO HAD A LONG-TIME STAFF
MEMBER AND IMPORTANT LEADER IN
THE PRECLINICAL BRANCH RETIRED
FROM FEDERAL SERVICE A COUPLE
YEARS AGO BUT THEN HAD BEEN
PART-TIME CONTRACTOR WITH US.
SHE ALSO OFFICIALLY COMPLETELY
REQUIRED.
WE HAD MIKE GILBRITH RETIRE AND
ROBERTA BLACK AND JUDY MILLER
HAVE TAKEN OVER.
I WANT TO TAKE A MOMENT AND TAKE
AND WANT TO THANK THOSE FOR THE
PRESENTATION FOR THIS AND JUST
AS A REMINDER OF OUR HIGH LEVEL
PRIORITIES AND YOU CAN SEE
THEY'RE DIVIDE INTO TWO MAJOR
AREAS AND THAT WILL BE HOW I
APPROACH SOME OF THE
ACCOMPLISHMENTS AS WELL AS THE
WAY FORWARD AS A REMINDER,
DEVELOPMENT OF HIV PREVENTION
PRODUCTS AND THE ATTENDANT
PIECES AND ISSUES THAT GO WITH
THAT CONTINUING TO FURTHER OUR
UNDERSTANDING OF THE BIOLOGY OF
HIV SUSCEPTIBILITY WHICH
HOPEFULLY DOES HELP US IN THE
DEVELOPMENT OF NEW PREVENTION
PRODUCTS.
IMPROVE ENGAGEMENT OF KEY
POPULATIONS AS I TALKED ABOUT
WITH THE SLIDE EARLIER AND AS WE
ALL KNOW THAT IS REALLY VERY
MUCH A CHALLENGE AND SOMETHING
THAT WE RECOGNIZE BUT REALLY
NEED TO DO IN PARTNERSHIP WITH
OTHER USG AGENCIES INCLUDING
C.D.C. AS WELL AS OTHERS.
AND THEN THINKING ABOUT THE
AREAS OF MATERNAL AND CHILD
TREATMENT T.B. AND CURE WHERE
ONE OF OUR MAJOR PRIORITIES IS
TO IMPROVE HIV TREATMENT AND
PREVENTION IN BOTH PREGNANT
WOMEN AND CHILDREN.
ALSO TO OPTIMIZE STRATEGIES TO
DIAGNOSE, TREAT AND PREVENT T.B.
IN THE MATERNAL AND PEDIATRIC
POPULATIONS AND CONTINUE TO
EVOLVE THE CURE RESEARCH IN
INFANTS AND CHILDREN.
THIS IS TO ILLUSTRATE TO YOU ALL
THAT WE HAVE A NUMBER OF
SOLICITED PROGRAMS THAT SPAN THE
DEVELOPMENT CASCADE ALL THE WAY
FROM DISCOVERY THROUGH CLINICAL
STUDIES.
I'LL BRING YOUR ATTENTION OVER
TO THE FAR RIGHT.
THERE WE HAVE THE NETWORKS
LISTED AS YOU ALL KNOW WE HAVE
THE MICROBECIDE NETWORK AND THE
CRITICAL WORK HAS MOVED IN
DECEMBER OF THE PAST YEAR.
AND THIS CONTINUES TO BE OUR
BASE FOR GAP FILLING ACTIVITIES
ALONG THE SPECTRUM FROM PRE
CLINICAL TO CLINICAL TESTING AND
LOOKING FORWARD TO MOVE THE NEXT
ITERATION APPROVED EARLIER IN
THE YEAR MOVING FORWARD.
AND I'LL TAKE SEVERAL SELECT
ACCOMPLISHMENT HIGHLIGHTS FROM
THE DIFFERENT AREAS THAT WE WORK
IN AND CERTAINLY NOT MEANT TO BE
ALL INCLUSIVE.
I WANT TO BEFORE I GO INTO THIS
I WANT TO SAY THAT NOT ONLY IS
IT THE STAFF IN PREVENTION
SCIENCES PROGRAM THAT
CONTRIBUTES TO ALL OF THE WORK
THAT WE DO, WE REALLY ARE VERY
MUCH MATRIXED FOR OUR WORK
ACROSS OUR WHOLE DIVISION OF
AIDS, THE SCIENTIFIC PROGRAMS AS
WELL AS OUR COLLEAGUES AND
ACROSS VARIOUS OTHER I.C.s
SPECIFICALLY NIMH AND OAR AND
OTHERS.
CARL TALKED ABOUT THE APPROVAL
FOR LONG ACTING CABOTEGRAVIR
REPRESENTS WORK ACROSS OUR
PHARMA PARTNERS.
THE SECOND BULLET RECOGNIZING
THE ONGOING SAFETY AND P.K.
TRIALS WE DO IN COLLABORATION
WITH OUR VACCINE RESEARCH
PROGRAM COLLEAGUES.
AND THAT IS MOST OF WHICH ARE
COLLABORATIONS BETWEEN THE EARLY
STUDIES CONTRIBUTING TO OUR
KNOWLEDGE BASE AS TO HOW TO MOVE
FORWARD IN THIS AREA.
SOME OF THE OTHER PIECES OF
CRITICAL WORK THE LAST BULLET
HERE IS ABOUT MTNO34 WHICH WAS A
STUDY IN ADOLESCENCE IN YOUNG
WOMEN IN SOME OF THE AFRICAN
SITES AND IT'S SOME OF THE
CRITICAL BRIDGING WORK AND
THERE'S ACTUALLY THREE OF THOSE
STUDIES.
THE OTHER COUPLE I'LL POINT OUT
AS WE GO LONG BUT THIS IS THE
WORK -- WE GO ALONG BUT TO
BRIDGE THE RING INTO THE
IMPORTANT POPULATIONS.
THIS WAS REPORTED OUT THIS PAST
YEAR THAT THE ADHERENCE IN THIS
YOUNGER GROUP WAS SURPRISINGLY
HIGHER THAN HAD BEEN FOR
OBSERVED IN THE ORIGINAL TRIALS
SO THAT WAS INFORMATION AS WELL
AS OTHER LESSONS LEARNED IN HOW
TO BEST CONDUCT STUDIES IN
ADOLESCENTS FROM THIS TRIAL.
AND MOVING ON TO THE 100 AND 200
MILLIGRAM INTRAVAGINAL RING
COMPARED TO THE ORIGINAL RING
WHICH WAS THE 28 DAY, 25 MILL
G
GRAMS.
ALL THREE WERE WELL TOLERATED
AND THERE WERE HIGHER
CONCENTRATIONS IN TISSUE AS WELL
AS FLUIDS.
PROBABLY NOT TERRIBLY SURPRISING
GIVEN THEY WERE HIGHER DOSAGES
BUT WAS IMPORTANT FOR US TO KNOW
THAT INFORMATION.
I'LL STAY ON AND JUMP DOWN HERE
TO THE THIRD BULLET STAYING ON
THE DAPIVIRINE RING AND IT'S
ALSO IMPORTANT TO THE LABELLING
FOR THAT PRODUCT.
THERE'S AN AREA MANY HAVE HEARD
ABOUT OVER THE YEARS.
SEVERAL OF THOSE GRANTS AND WE
HEARD THE PRODUCTS AND WHAT WE
ARE LEARNING ABOUT THESE
DELIVERY SYSTEMS FOR HIV
PREVENTION PRODUCTS AND WE CAN
TAKE THAT KNOWLEDGE WITH US AS
WE MOVE FORWARD.
AND THERE'S A STAFF IN OUR GROUP
AND ACROSS THE DIVISION WHO
ORGANIZED A PREGNANCY WORKSHOP
TO GATHER STAKEHOLDERS TO
DISCUSS WHAT THE BARRIERS AND
CHALLENGES ARE AND SOME OF THE
WAYS FORWARD.
ALSO, FOLKS WITHIN OUR GROUP
PARTICIPATED IN THE W.H.O. AND
IMPACT CALL TO ACTION THE
WORKING GROUP ON ACCELERATING
INCLUSION OF PREGNANT WOMEN INTO
ANTIRETROVIRAL STUDIES AND THIS
IS BUILDING ON THE IMPORTANT
WORK FROM THE PREGLAC GROUP YOU
ALL ARE PROBABLY FAMILIAR WITH
THAT WAS LED BY NIH ACROSS USG
AGENCY GROUPS THAT MET FOR QUITE
SOME TIME AND CAME FORWARD WITH
RECOMMENDATIONS ABOUT RESEARCH
IN GENERAL IN PREGNANT WOMEN.
AND MOVING TO CHILDREN, THE
IMPACT STUDY THE P.K. DATA
RESULTED IN A RAPID
COMMUNICATION ON THE USAGE IN
YOUNG CHILDREN FOR MDRTB AND
THERE'LL BE COMMUNICATIONS
COMING FORWARD ON MORE SPECIFIC
DOSING MOVING THROUGH THIS YEAR.
[AUDIO DIGITIZING]
AND FOR THE SUBMISSION THE
TREATMENT FOR ADOLESCENTS AND
THE IMPACT 2014 FOR TREATMENT IN
ADOLESCENTS AS WELL.
WE ALSO COLLABORATED WITH OUR
BASIC SCIENCES PROGRAM
COLLEAGUES TO LAUNCH THE FIRST
PEDIATRIC FOCUS COLLABORATORY.
YOU CAN SEE THE LOGO AT THE
BOTTOM THE PAID COLLABORATORY.
AND WE'VE TALKED ABOUT THE
INCLUSION OF PREGNANT WOMEN
EARLIER IN HIV RESEARCH BOTH
PREVENTION AND TREATMENT AND
PLEAD TO REPORT THE STUDY HAS
THREE COHORTS WORKING BACKWARD
IN GESTATION STARTING IN COHORT
1 WITH THE WOMEN OF THE 36 TO 37
WEEKS.
THAT COHORT WAS COMPLETED.
IT'S LOOKING AT DAPRIVIRINE
INTRAVAGINAL RING AND THE ORAL
USAGE AND COHORT 2 IS IN
PROGRESS AND HOPING TO COMPLETE
THAT ENROLLMENT BY THE BEGINNING
OF MARCH.
I TALKED WITH THE FACT THAT THE
DAPRIVIRINE ARE CRITICAL
INFORMATION FOR THESE
POPULATIONS MOVING FORWARD FOR
APPROVALS.
AND AS POINTED OUT WITH THE
EARLIER SLIDES WE'VE MOVED INTO
AWAY FROM SOME TOPICAL
PREVENTION AND IT'S IMPORTANT WE
HAVE THIS INFORMATION BOTH TO
COMPLETE THIS WORK ON
DAPRIVIRINE AND ON THE DELIVERY
SYSTEMS THAT POINTED OUT FROM
OTHERS THAT INFORM PREVENTION,
PRODUCT DEVELOPMENT MOVING
FORWARD AND A LOT OF THIS
INFORMATION WILL BE HELPFUL AS
WE MOVE INTO THAT WORK.
AND WE LOOK AT THE MAJOR GAPS IN
HIV PREVENTION RESEARCH.
ON THE ONE HAND A LOT OF HAS
CHANGED IN THE PAST YEAR AS YOU
CAN SEE FROM IS THE SELECT
HIGHLIGHTS.
A LOT'S BEEN ACCOMPLISHED BUT WE
WERE ALREADY AWARE LAST YEAR OF
THE FACT THAT THESE WERE GOING
TO BE THE CHALLENGES THAT WE
WERE FACING.
AND PARTICULARLY ABOUT ADVANCING
AND MARY BROUGHT THIS UP IN HER
PRESENTATION THE CHALLENGES OF
ADVANCING THE NEXT GENERATION OF
PREVENTION PRODUCTS INTO HUMAN
CLINICAL TESTING AND DOING THAT
IN WAYS THAT GET US THE ANSWERS
THAT WE NEED AND ARE FEASIBLE TO
DO.
CABOTEGRAVIR WILL HOPEFULLY BE
AVAILABLE SOON AND EFFECT HOW WE
DO OUR TRIALS MOVING FORWARD AND
AS SHE SAID WE CANNOT CONTINUE
TO RELY ON CLINICAL TRIAL
METHODOLOGY.
THE RESOURCES BECOME PROHIBITIVE
AND AS WELL AS THE TIME AND
SOMETHING WE HAVE TO CONTINUE
FOCUS ON HOW TO INCREASE CHOICE
ACROSS POPULATIONS IN NEED OF
HIV PREVENTION PRODUCTS AND DO
THAT IN A WAY THAT IS FEASIBLE
AND TIMELY.
AND WE HAVE SPOKE WITH
COLLEAGUES ABOUT INTEGRATING
BEHAVIORAL AND SOCIAL SCIENCE
INTO REALLY ALL OF OUR STUDIES
WE HAVE ALSO WORKED WITH OUR
CONTRACT IN THE LAST COUPLE OF
YEARS ON SOME ETHNIC STUDIES ON
YOUNG GIRLS AND WOMEN IN SOUTH
AFRICA TO BETTER UNDERSTAND
DECISION MAKE AND HOW TO CREATE
DESIRE FOR PREVENTION PRODUCTS
IN THIS POPULATION.
IT'S VERY CLEAR TO US WE'RE
GOING TO NEED TO WE'RE GOING TO
TAKE THE NEXT STEPS AND EXPAND
THE POPULATIONS WE'RE FOCUSSING
ON TO BETTER UNDERSTAND AND
ENGAGE KEY POPULATIONS AS A
CHALLENGE AROUND REQUIRED MUCH
MORE INNOVATION AND SIGNIFICANT
PARTNERSHIP AND THEN MAKING SURE
THAT WE'RE FILLING EARLY
PREVENTION GAPS.
WE HAVE A NUMBER OF UNSOLICITED
GRANTS AS WELL AS SOLICITED
PROGRAMS.
AROUND NOTICE AREA OF PREVENTION
RESEARCH AND THE CLINICAL
PREVENTION RESEARCH IS THE HIV
PREVENTION TRIALS NETWORK, THE
HP10 AND THE MAJOR SPECIFIC AIMS
ARE VERY MUCH ALIGNED WITH WHAT
WE'RE TRYING TO ACCOMPLISH IN
OUR PROGRAM.
NOVEL HIV PREVENTION METHODS AND
IMPROVING DELIVERY SYSTEMS AND
INTEGRATED AND SOCIO BEHAVIORAL
PREVENTION STRATEGIES WHICH ARE
KEY TOTALLY NECESSARY TO BEING
ABLE TO IMPLEMENT THIS WORK AND
CONSIDER THE WHOLE PERSON.
BUT I THINK THOSE OF YOU WHO
HAVE WORKED IN THIS AREA ALSO
RECOGNIZED THERE'S A NUMBER OF
CHALLENGES OFTEN TIMES WE ARE
LOOKING AT COMMUNITY RANDOMIZED
STUDIES, FACILITY RANDOMIZED
STUDIES WHICH ARE NEEDED BUT
PRESENT THEIR OWN CHALLENGES AND
THIS IS AN AREA THAT I THINK
WE'VE GOT TO BE WORKING TOGETHER
ON THINKING A LOT MORE AS WE
ALWAYS ARE THIS IS AN AREA TO
OPTIMIZE FOR SURE AS WE MOVE
FORWARD.
OPTIMIZING PATERNAL AND CHILD
REGIMENT S AND GETTING APPROVALS
AND LICENSURE FOR TREATMENTS IN
THE MATERNAL AND CHILD
POPULATIONS AND HIV AND T.B. IS
OFTEN YEARS BEHIND NON-PREGNANT
ADULTS.
WE'RE VERY FOCUSSED ON MOVING
THAT FORWARD.
ONE ISSUE IS CHILD FRIEND LLY
FORMULATIONS FOR THE YOUNGEST
CHILDREN AND INCLUDING PREGNANT
AND LACTATING WHICH WE'RE
COMMITTED TO THINK OF
ADOLESCENTS BEING SENSITIVE TO
THEIR NEEDS AS WE THINK NOT ONLY
OF THE PRODUCTS AND
IMPLEMENTATION BUT THE TRIALS
ARE BEING CONDUCTS AND LOGISTICS
AND CONTINUING OUR PROGRESS
TOWARDS HIV-FREE REMISSIONS IN
THE YOUNGEST POPULATIONS.
AND THIS ALIGNS WITH WHAT WE'RE
TRYING TO ACCOMPLISH IMPROVING
TREATMENT OF HIV AS WELL AS T.B.
PREVENTION AND TREATMENT
FOCUSSING ON COMPLICATIONS AND
CO-INFECTIONS OF IMPORTANCE IN
THESE POPULATIONS AND MOVING
TOWARDS ART-FREE REMISSION.
I WANTED TO POINT OUT I SEE THIS
AS A MAJOR OPPORTUNITY FOR US
REALLY PROVIDES ALL THESE
DIFFERENT SERVICES, THE GAP
FILLING SERVICES AND THE
PRECLINICAL AREA AND ANIMAL
MODELS AND BIO ANALYTICAL
SUPPORT, MANUFACTURING, QUALITY
SUPPORT AND THEN AS I MENTIONED
SPECIFICALLY THE ETHNOGRAPHIC
WORK AND OPPORTUNITIES MOVING
FORWARD.
THAT JUST BRINGS US BACK TO OUR
PRIORITIES.
VERY BRIEFLY, I WANTED TO
MENTION A COUPLE THINGS IN THE
COVID WORK SINCE LAST YEAR.
ONE, AS I THINK YOU ALL
REMEMBER, WE WORKED ON WITH
REGENERON ON THEIR STUDY FOR
PREVENTION AND THAT EUA WAS AIM
TO BE EXPANDED TO INCLUDE
POST-EXPOSURE PROPHYLAXIS BASED
ON THE CO-VPN STUDY.
WE RECENTLY I'M PROUD TO SAY
COMPLETED ENROLLMENT OF IMPACT
2032 THE REMDESIVIR STUDY IN
P.K. AND PREGNANT WOMEN AND MORE
COMING ON THAT HOPEFULLY BEFORE
LONG AND HAD STAFF THAT WORKED
ON COVID AND STAFF WHO WORKED
WITH DMID ON THE VACCINE STUDIES
IN PREGNANT WOMEN.
THANK YOU VERY MUCH AND I'M
HAPPY TO TAKE QUESTIONS.
>> THANK YOU, SHERYL, THAT WAS
GREAT AND IMPORTANT FOCUS ON KEY
POPULATIONS AND THE PREVENTION
MODALITIES.
AUDREY, QUESTION THEN STEPHAUN.
>> IT WAS EXCITING TO SEE WHERE
YOU ALL SEE ADOLESCENTS AND I
GUESS COMBINATION PREVENTION
FITTING IN THE AGENDA.
THAT'S EXCITING.
I'M CURIOUS WITH WITHDRAWAL OF
THE RING HOW YOU ALL ENVISION
THAT PLAYING OUT BECAUSE I KNOW
IN SOME OF THE WORK WE'VE BEEN
DOING COLLEAGUES ARE SEEING THE
RING CONTINUING TO BE PART OF
THE CHOICE.
HOW DOES IT FIT WITH NIH PART OF
THE FUNDING MECHANISM AND THE
SECOND PART, FOR THE CONTRACT
ETHNOGRAPHIC WORK HAVE YOU
TALKED ABOUT RFAs IN THAT SPACE?
I KNOW COLLEAGUES EXCITED TO DO
THAT AND I'M SURE THERE'S SXE D
EXPEDIENCY REASONS FOR USING
CONTRACTORS.
.
>> STARTING WITH THE SECOND
QUESTION FIRST, YOU'RE RIGHT.
TO GET THINGS GOING IT WAS AN
EFFICIENT WAY TO MOVE FORWARD AS
AS QUICKLY AS POSSIBLE.
THE ETHNOGRAPHIC WORK.
THAT'S EXACTLY WHAT WE'RE
FOCUSSING ON RIGHT NOW, OKAY,
WHAT ARE THE NEXT STEPS.
TAKING WHAT WE'VE LEARNED AND
MAKING SURE WE DISSEMINATE THAT
BOTH TO THE SCIENTIFIC COMMUNITY
BUT REALLY TO HOPEFULLY THE
PIECES OF INFORMATION THAT WILL
BE USEFUL TO HAVE IMPLEMENTERS
THAT MAYBE WE'VE ALREADY LEARNED
AND CLEARLY THERE ARE NEXT STEPS
AND WHAT SHOULD THOSE BE.
I KNOW WE'RE CONSIDERING HAVING
A DISCUSSION AND POTENTIALLY
WORKSHOP BUT MORE TO COME ON
THAT AS WE MOVE FORWARD BUT
YOU'RE EXACTLY RIGHT.
BACK TO THE DAPRIVIRINE RING
QUESTION.
NIH AS I SAID IS VERY MUCH
COMMITTED TO COMPLETING THESE
BRIDGING STUDIES WHICH WILL BE
REQUIRED TO MOVE IT FORWARD.
I THINK THE RING RECEIVED
APPROVAL A YEAR, YEAR AND A HALF
AGO AND WHO PRE-QUALIFICATION.
I WILL SAY THE REGULATORY
SPONSORS FOR ALL OF THAT WORK I
DON'T WANT TO SPEAK FOR THEM.
I DO KNOW THEY ARE VERY
COMMITTED TO AS ARE WE, TO
MAKING SURE THAT THERE'S CHOICE
FOR POPULATIONS AND REALLY ALL
POPULATIONS BUT PARTICULARLY AS
YOU POINTED OUT SUB-SAHARAN
AFRICA WHERE MUCH MORE CHOICE IS
NEEDED AND WE NEEDED TO GET
EVERY AVAILABLE POSSIBILITY OUT
THERE.
I KNOW THEY HAVE FILED AND/OR
ARE PLANNING ON FILING IN
VARIOUS COUNTRIES IN SUB-SAHARAN
AFRICA AND MY UNDERSTANDING IS
THE EXPECT TO SEE THOSE THROUGH
AND WE HOPE THEY'LL BE ABLE TO
MOVE FORWARD.
>> AND WOMEN MAY BE ALLOWED TO
USE THE PRODUCT AND ANYWAY, I'M
SURE IT WILL BE INTERESTING TO
SEE HOW IT UNFOLDS.
>> MORE TO COME ON THAT.
I'M CERTAIN.
>> IMPORTANT DISCUSSIONS.
STEPHAUN, LAST QUESTION FOR
SHERYL.
>> AUDREY ASKED MY QUESTION SO
JUST A COMMENT TO SAY I THINK
IT'S REALLY IMPORTANT AND I GOT
FROM YOUR SLIDE THAT TALKING
ABOUT THE IMPORTANCE OF
COMMUNITY ENGAGEMENT AND I THINK
THAT'S BEEN A THEME IN THIS
MEETING AND OTHER MEETINGS.
I THINK IT'S IMPORTANT ALSO TO
CONSIDER THE COMPLICATED NATURE
OF CLINICAL TRIALS AND WITH THE
ONGOING DISCUSSIONS HOW TRIALS
WILL BE DESIGNED GOING FORWARD,
I WANTED TO COMMUNICATE HERE
THAT I THINK IT'S REALLY
IMPORTANT THAT COMMUNITIES ARE
ENGAGED IN THESE CONVERSATIONS
MEANINGFULLY SO PEOPLE CAN
UNDERSTAND WHAT'S HAPPENING IN
THE ENTERPRISE AND HOW THINGS
ARE MOVING FORWARD.
I WANTED TO MAKE THAT COMMENT.
>> THANK YOU.
COULDN'T AGREE MORE.
I THINK THAT'S ALWAYS BEEN THE
CASE.
WE'VE SEEN OVER THE PAST COUPLE
YEARS IT'S BECOME MORE
IMPORTANT.
VERY COMMITTED TO THAT.
>> THANK YOU FOR BRINGING THAT
UP.
VERY IMPORTANT POINT.
OKAY.
WE ARE GOING TO KEEP MOVING AND
I'M GOING TO TURN IT OVER FOR
THE OFFICE OF CLINICAL SITE
OVERSIGHT REPORT.
>> MY NAME IS MANIZHE PAYTON OF
THE DIVISION OF AIDS SUPPORTING
THE SCIENTIFIC AND PROGRAMMATIC
PRIORITIES ACROSS THE DIVISION.
I'LL GIVE AN OVERVIEW AND WE ARE
GIVING OVERALL SITE CAPABILITIES
AND PERFORMANCE.
WE DO THIS BY WORKING WITH EACH
OF THE FOUR SCIENTIFIC PROGRAMS
OF AIDS INCLUDING THE VACCINE
PROGRAM AND PREVENTION PROGRAMS
AND AS WELL AS WITH OUR
COLLEAGUES IN THE OFFICE OF
POLICY AND CLINICAL RESEARCH
OPERATIONS.
WE COLLABORATE EXTENSIVELY
INTERNALLY AND EXTERNALLY TO
ACHIEVE OUR MISSION.
EXTERNALLY WE WORK WITH OUR
COLLEAGUES AT THE AIDS NETWORK
AND COMMUNITY STAKEHOLDERS AND
CLINICAL SITES WORLDWIDE.
WE HAVE A TALENTED GROUP OF
INDIVIDUALS IN OUR OFFICE
PASSIONATE ABOUT SUPPORTING OUR
SITES AND OUR MISSION.
THEY'VE DEMONSTRATED
EXTRAORDINARY FLEXIBILITY SINCE
THE BEGINNING OF THE PANDEMIC
AND MANY HAVE TAKEN ON
ADDITIONAL RESPONSIBILITIES
RELATED TO COVID RESEARCH.
THEY'VE BEEN ABLE TO PIVOT
QUICKLY AND TRAILED BLAZED TO
COME UP WITH WAYS TO INNOVATE IN
THIS ENVIRONMENT.
THE OFFICE IS LED BY MYSELF AND
THE DEPUTY DIRECTOR OF OUR
OFFICE.
AND OUR OFFICE CONSISTS OF FOUR
BRANCHES.
START FROM THE LEFT, THE ASIA
AMERICAS BRANCH AND THE AFRICA
AND DOMESTIC PARTNERS BRANCH.
THEY'RE BOTH STAFFED BY PROGRAM
OFFICERS THAT MANAGE A PORTFOLIO
OF COMPETITIVE GRANTS CONTAINING
DAIDS, HIV/AIDS SITES AND THEY
FORM THE ENTERPRISE.
THEN WE HAVE THE MONITORING
OPERATIONS BRANCH.
THIS BRANCH OVERSEES THE
MONITORING FUNCTION ACROSS ALL
DAIDS CLINICAL RESEARCH SITE TO
FULFILL OUR REGULATORY
RESPONSIBILITY AS A SPONSOR TO
ENSURE PROTOCOL REQUIREMENTS,
REGULATIONS AND INTEGRATE OF
DATA AND SAFETY OF PARTICIPANTS.
THE FOURTH IS THE PHARMACEUTICAL
AFFAIRS BRANCH.
THE BRANCH IS STAFFED WITH
TRAINED PHARMACISTS AND PHARMACY
SPECIALISTS WHO PROVIDE
PHARMACEUTICAL PRODUCT EXPERTISE
TO TEAMS AND OVERSEE AND SUPPORT
ALL THE SITE PHARMACIES IN
CONDUCTING DAIDS SPONSORED
CLINICAL TRIALS.
THE CORE BUSINESS IS DESCRIBED
HERE.
FIRST RESPONSIBLE FOR MONITORING
AND SITE OVERSIGHT FOR OVER 200
SITES WORLDWIDE.
WE MONITOR THE SITES TO FULFILL
OUR REGULATORY RESPONSIBILITY AS
A SPONSOR AND ASSURE THE SAFETY
OF PARTICIPANTS AND DATA
QUALITY.
OUR STAFF EACH HAVE A PORTFOLIO
OF BETWEEN 15 AND 20 CLINICAL
RESEARCH SITES AND THE
ASSOCIATED GRANTS FOR WHICH THEY
HAVE OVERSIGHT RESPONSIBILITY.
AND AS YOU KNOW EACH OF OUR
SITES CAN PARTICIPATE IN UP TO
FOUR OF THE HIV/AIDS NETWORKS
AND WORK CLOSELY WITH THE SITES
TO FACILITATE THE INDIVIDUAL
CHALLENGES AND CONTEXTUAL ISSUES
TO ALLOW THEM TO OPTIMALLY
PARTICIPATE.
THE MONITORING IS OUT SOURCED TO
A CONTRACTOR CURRENTLY PPD OUR
EYES AND EARS ON THE GROUND
PERFORMING THE ON SITE AND IN
REMOTE MONITORING ACTIVITIES.
AND CURRENTLY, DAIDS IS
MONITORING OVER 90 CLINICAL
TRIALS.
AND SEVERAL DAIDS SPONSORED
TRIALS CONTRIBUTED DATA TO
MARKETING AUTHORIZATION
APPLICATIONS AND TRIGGERED
REGULATORY INSPECTIONS AT THESE
SITES.
THE SITES HAVE BEEN INSPECTED BY
THE USFDA, EUROPEAN MEDICINES
AGENCY, THE AMA AND MANY
NATIONAL REGULATORY AUTHORITIES
OUTSIDE THE U.S. SUCH AS THE
SOUTH AFRICA HEALTH PRODUCTS
REGULATORY AUTHORITY THE THAI
FDA AND MANY OTHER REGULATORY
AUTHORITIES.
IN ADDITION THE PHARMACEUTICAL
AFFAIRS BRANCH HAS DISTRIBUTION
AND MANAGEMENT OF STUDY SITES
AND IT'S INTEGRAL TO THE TEAM
AND WORK WITH THE TEAMS TO
DEVELOP AND OVERSEE STUDY
PRODUCT REQUIREMENTS.
WORKING VERY CLOSELY WITH OUR
CONTRACTOR, OUR CLINICAL
RESEARCH PRODUCT MANAGEMENT
CENTER DISTRIBUTES STUDY PRODUCT
IN THE HIGHLY REGULATED
ENVIRONMENT AND CURRENTLY
DISTRIBUTE STUDY PRODUCT TO 27
COUNTRIES WORLDWIDE AND ARE
COUNTING.
OVER THE PAST FEW YEARS THE
PANDEMIC HAS HAD US LOOK AT
NOVEL WAYS OBTAIN OUR GOALS AND
IT'S NOT OPTIMAL FOR OPERATING
IN A PANDEMIC VARIETY AND
CONTINUE TO EVALUATE AND ASSESS
OUR ORGANIZATIONAL PRIORITIES TO
ENSURE THEY CONTINUE TO REMAIN
RELEVANT AND PRACTICAL FOR THESE
TIMES.
AND THE FIRST IS TO IMPLEMENT
REMOTE APPROACHES TO OVERSIGHT.
WE ACKNOWLEDGE WE'RE OPERATING
IN A CON TRAVESTRAINED SITES AND WE
MAINTAIN A REGULATORY
RESPONSIBILITY TO PERFORM
MONITORING AND IMPLEMENTED A
REMOTE MODEL THAT FACILITATES
REMOTE MONITORING.
OUR MODEL CONTINUES TO EVOLVE
BASED ON FEEDBACK FROM OUR
EXTERNAL STAKEHOLDERS.
IN ADDITION, DAIDS IS EVALUATING
HOW TO INCORPORATE A CENTRALIZED
MONITORING COMPONENT TO OUR
ENTERPRISE TO STRENGTHEN OUR
OVERSIGHT OF PATIENT SAFETY,
INTEGRATE AND DATA QUALITY.
OUR ABILITY TO INTERACT ON SITE
HAS DIMINISHED AND THAT IMPACTS
SEVERAL FORMS WE PLANNED TO
PROVIDE TRAINING AND SUPPORT TO
SITES ON ISSUES SUCH AS DAIDS
REQUIREMENT AND INVESTIGATOR
RESPONSIBILITIES.
WE'RE PLANNING TO HOST A VIRTUAL
SITE TRAINING EVENT THIS YEAR TO
PROVIDE RESEARCH TRAINING IN AN
INTERACTIVE MANNER TO FACILITATE
REMOTE PARTICIPATION.
THE TIMING IS SUBJECT TO
CHANGING EVENTS AROUND THE
PANDEMIC.
OUR OFFICE IS GROUNDED IN THE
PRINCIPLE OF PARTNERSHIP AND
ENGAGEMENT WITH OUR STAKEHOLDERS
INTERNALLY AS WELL AS EXTERNALLY
WITH OUR NETWORK, COMMUNITY AND
SITE COLLEAGUES.
WE CAN'T ADVANCE THESE
INITIATIVES WITHOUT CLOSE
COLLABORATION WITH OUR PARTNERS.
THEIR FEEDBACK IS INSTRUMENTAL
IN DEFINING OUR PATH FORWARD.
WE'VE ALSO BEEN INVOLVED IN
ADVANCING THE NIAID RESEARCH
AGENDA.
OUR OFFICE IS INVOLVED IN THE
ACTIV 2 PROJECT DRIVING FORWARD
SITE ACTIVITIES AND MONITORING
AND STUDY PRODUCT DISTRIBUTION
AND MANAGEMENT FOR THE COVID
TREATMENT PROTOCOL.
LASTLY, WE RECOGNIZE WE'RE
SEEING IF THERE'S OPPORTUNITIES
FOR US TO SUPPORT OUR SITES AND
FACILITATE THEIR PARTICIPATION
IN RESEARCH THIS MEANS BEING
FLEXIBLE WITH TIME LINES AND
BRINGING INFORMATION TO SITE
FORUMS AND LISTENING TO OUR
SITES ABOUT THEIR SPECIFIC
NEEDS.
AS WE LOOK FORWARD, WE'RE
PLANNING TO USE THE LESSONS
WE'VE LEARNED TO EVOLVE OUR
PROCESSES TO SUPPORT THIS
CHANGING LANDSCAPE.
WE CONTINUE TO SYSTEMICALLY LOOK
AT ESTABLISHMENT OF SITES, NEW
LOCATIONS WHERE RESEARCH IS
CONDUCTED, MONITORING ACTIVITIES
AS WELL AS PHARMACY SUPPORT.
WE'RE GROUNDED IN LISTENING TO
OUR STAKEHOLDERS AND ANALYZING
THEIR FEEDBACK TO INFORMING
REFINEMENTS TO THEIR PROCESSES.
WE WANT TO CONTINUE TO PARTNER
WITH SITES AND WE KNOW SITES ARE
NOT PERFORMING AT OPTIMAL
CAPACITY BECAUSE OF SOME OF
THESE CHALLENGES SUCH AS SUPPLY
CHAIN ISSUES OR STAFFING
CHALLENGES AND THESE CHALLENGES
IMPACT SITE PERFORMANCE.
WE WANT TO CONTINUE TO DIALOGUE
WITH THE SITES TO UNDERSTAND THE
NATURE OF THESE CHALLENGES TO
DETERMINE HOW WE MAY BE ABLE TO
BETTER SUPPORT THEM AND JOINTLY
WORK ON SOLUTIONS.
WE STRIVE TO BE TRANSPARENT AND
PRACTICAL IN OUR APPROACHES TO
FULFILLING OUR REGULATORY
RESPONSIBILITIES.
AND WE CAN'T DO EVERYTHING AT
ONCE.
WE ALSO WORK WITH OUR
STAKEHOLDERS INTERNALLY AND
EXTERNALLY TO PRIORITIZE
IMPLEMENTATION FACILITATING
DAIDS SCIENTIFIC PRIORITIES.
SO WITH THAT, I'M GOING TO
CLOSE.
THIS IS A BRIEF OVERVIEW OF OUR
OFFICE AND WHERE WE'RE HEADED
AND I'M HAPPY TO TAKE ANY
QUESTIONS.
THANK YOU.
>> IT'S BEEN A NICE OVERVIEW AND
IT'S BEEN A CHALLENGING TIME TO
TRY TO DO THIS AND APPRECIATE
YOUR EFFORTS TO MAINTAIN THESE
SITES AND NETWORKS AMIDST ALL
THE COMPLEXITIES.
THANK YOU.
QUESTIONS?
IF PEOPLE THINK OF QUESTIONS
AFTERWARDS YOU CAN REACH OUT BY
EMAIL.
>> GREAT AND IMPORTANT WORK.
THE QUALITY OF DATA COLLECTION
AND SAMPLE COLLECTION AND
MANAGING THE OPERATIONS OF
CLINICAL TRIALS IS REALLY
IMPORTANT.
WHAT DO YOU SEE AS MAJOR GAPS IN
HELPING YOU FULFILL A MISSION OF
OPTIMIZING OPERATIONS AND USING
DIGITAL PLATFORMS TO HAVE REAL
TIME DASHBOARDS TO SEE HOW
QUALITY IS GOING AND HOW WELL
THEY'LL BE DOING AND MANAGING
OUR TRIALS?
>> THERE'LL ALWAYS BE TECHNOLOGY
TO GIVE US THE PROGRESS OF OUR
TRIALS AND DATA.
ONE OF THE IMPORTANT INITIATIVES
IS THE CENTRALIZED MONITORING
INITIATIVE WHERE WE'LL BE ABLE
TO APPLY STATISTICAL
METHODOLOGIES TO DATA QUALITY
AND TO THE DATA TO ASSESS THE
QUALITY OF DATA AND IDENTIFY
TRENDS THAT REMOVE OUR
REQUIREMENT TO BE ON SITE OR TO
PERFORM SOME OF THE TRADITIONAL
ONSITE MONITORING.
WE'RE EXCITED TO GET THAT OFF
THE GROUND.
THERE'S ALSO INITIATIVES IN
TERMS OF REMOTE ACTIVITIES THAT
CAN BE PARTICIPANT FACING,
ELECTRONIC INFORMED CONSENT TO
HELP FACILITATE THE AND THE
ADVANCEMENT OF SOME OF THE
ANALYTICS THAT MAY BE AVAILABLE
TO US TO BE ABLE TO TREND
PROGRESS TO BE ABLE TO LOOK AT
PORTFOLIOS AND CAPACITY OF
SITES.
THAT'S BEEN CHALLENGING FOR US
TO BE PREDICTIVE ABOUT CAPACITY
AND WHAT THE DRIVERS OF CAPACITY
ARE AT THE SITES BUT WE'RE STILL
TRYING TO COBBLE TOGETHER THE
CHARACTERISTICS OF SITES TO BE
ABLE TO SEE IF THERE'S ANY WAY
WE CAN GATHER ANY INFORMATION
ABOUT WHAT SOME OF THE DRIVERS
MIGHT BE ONE OF THE KEY DRIVERS,
SOME OF THE KEY DRIVERS.
THAT'S A LONG TERM GOAL.
WE'VE BEEN TREMENDOUSLY
IMPRESSED BY THE DEDICATION AND
PERSEVERANCE OF THE SITES TO
CONTINUE.
IT'S BEEN A MOTIVATING AND
INSPIRING TO SEE THE DEDICATION
OF THE FOLKS ON THE GROUND AND
WE REALLY -- PART OF WHAT WE'RE
DOING IS JUST LISTENING AND
EMPATHIZING AND UNDERSTANDING
WHAT THE ISSUES ARE TO TRY TO
SEE HOW WE MAY BE ABLE TO WORK
WITH THEM TO SOLUTION.
>> REMARKABLE ON BOTH SIDES.
WE ARE GOING TO FINISH UP WITH
THE REPORT AND THE OFFICE OF
POLICY AND OPERATIONS.
>> THANK YOU FOR THE
OPPORTUNITY.
I PROMISE TO BE BRIEF GIVEN THIS
IS THE FINAL PRESENTATION.
SO WHAT I WANT TO DO IS GIVE AN
EVERY VIEW OF THE AIDES OFFICE
FOR POLICY AND CLINIC RESEARCH
ALSO KNOWN AS OPCRO.
I'M GOING TO START BY GIVING A
HIGH LEVEL INTRODUCTION OF CROW
AND TALKING ABOUT THE HIV
CLINICAL TRIALS NETWORK
PORTFOLIO AND IN TALKING ABOUT
THE KEY INFRASTRUCTURE CONTACTS
AND WHAT OUR ROLE HAS BEEN IN
SPONSOR OVERSIGHT FOR ACTIV 2.
SO THIS IS THE DAIDS
ORGANIZATIONAL STRUCTURE AND
DIDN'T THINK I'D BE THE FIRST TO
SHOW THIS.
ON THE FAR LEFT IS OPCRO OF
WHICH I'M THE DIRECTOR AND THE
SCIENTIFIC PROGRAMS ARE LAID OUT
THERE AND THEN OXO.
SO AS WITH THE OFFICE OF
CLINICAL SITE AND OVERSIGHT WE
COLLABORATE ACROSS THE DIVISION
AND SINCE MOST OF OUR RESOURCES
ARE GEARED TOWARDS THE CLINICAL
TRIALS NETWORKS WE WORK WITH
PREVENTION SCIENTISTS AND THE
VACCINE PREVENTION PROGRAMS NOT
SO MUCH WITH BASIC SCIENCES AND
NOW WE DON'T EVEN PASS EACH
OTHER IN THE HALLWAY.
WE'RE VERY DIVERSE GROUP
ORGANIZED INTO FOUR TEAMS AND
THREE BRANCHES.
THE FOUR TEAMS COME UNDER THE
OPCRO OFFICE OF THE DIRECTOR.
WE DEAL WITH POLICIES AND
PROCEDURES INCLUDING REGULATORY
COMPLIANCE AND WE DO IT BY
OVERSEEING MONITORING AND
REPORTING IN OUR TEAM AND
CLINICAL TRIALS AGREEMENTS AND
OTHER AGREEMENTS IN OUR CTA
TEAM.
DATA MANAGEMENT AND TRIAL MASTER
FILE OVERSIGHT WHICH IS THE
NEWEST TEAM IN THE OFFICE OF THE
DIRECTOR.
WE HAVE THE CLINICAL RESOURCES
BRANCH IN WHICH AND THIS ALLOWS
US TO DO OUR WORK.
SO THAT BRANCH SERVES AS A
TECHNICAL INTERFACE TO ENSURE
APPROPRIATE DELIVERY OF SERVICES
ACCORDING TO CONTRACT
REQUIREMENTS AND THEY ALSO
REVIEW THE RESOURCE REQUIREMENTS
FOR CLINICAL TRIALS AND
COORDINATE ACCESS TO RESOURCES
WITHIN DAIDS ACCESS TO THE
CONTRACT RESOURCES AND PROVIDE
RESOURCES FOR CLINICAL RESEARCH
TRAINING IN SEARCH SITUATIONS.
AND THE BRANCH PROVIDES
REGULATORY MANAGEMENT AND
GUIDANCE AND SURVEILLANCE.
THE MEMBERS SERVE AS AUTHORIZED
REPRESENTATIVES AND THEY'RE THE
LIAISONS WITH HEALTH AUTHORITIES
PARTICULARLY THE FDA THERE IS IS
THE PROTOCOL REGISTRATION TEAM.
IN MATERIALS OF HUMAN SUBJECT
PROTECTION OVERSIGHT IS LOCATED
IN A BRANCH WHICH STANDS FOR
PROTECTION OF PARTICIPANTS,
EVALUATION AND POLICY AND EASIER
TO REMEMBER THE HUMAN SUBJECTS
PROTECTION AND POLICY AND
PROVIDE SUBJECT MATTER EXPERTISE
INCLUDING IRB AND ETHICS
REQUIREMENTS AND DEVELOP AND
MAINTAIN DAIDS POLICY DOCUMENTS.
THERE ALSO ARE OFFICIAL LIAISON
TO THE HHS OFFICE OF HUMAN
PROTECTIONS.
WE DEPEND ON GOOD COLLABORATION.
WE WE'RE INTENSELY COLLABORATIVE
INSIDE DAIDS AND OUTSIDE OF
DAIDS.
THIS IS AS TYPICAL AS YOU CAN BE
OF A MODEL OF HOW UPDATES
OVERSIGHT OF TRIALS.
WE PROVIDE FUNDING TO OUR
CLINICAL TRIALS NETWORKS AND
SOME FUNDING AS WELL TO THE
CLINICAL RESEARCH SITE
ASSOCIATED WITH THAT NETWORK.
THEN THE NETWORK IS RESPONSIBLE
FOR THE CONDUCT OF THE TRIAL.
THERE'S A LEADERSHIP AND
OPERATIONAL CENTER AND
LABORATORY CENTER AND WE
COLLABORATE WITH ALL OF THOSE
AND THIS IS A SCHEMATIC THAT
SHOWS DIFFERENT PHASES OF THE
TRIAL OF A NETWORK TRIAL.
WE PARTICIPATE LESS IN PROTOCOL
INFORMED CONCEPT DEVELOPMENT
UNLESS BY CONSULT OR THERE'S AN
NIAID AND NEED FOR A PRE-NIAID
MEETING AND REGULATORY AFFAIRS
PARTICIPATES AND WE START TO
PARTICIPATE MORE HEAVILY WHEN WE
GET TO SCIENTIFIC REVIEW.
WE PROVIDE SEVERAL OF OUR GROUPS
FOR FORMAL COMMENTS AND HSP AND
THE PHARMACO VIGILANCE TEAM AND
THERE'S A NUMBER OF ACTIVITIES
AS THE TRIAL FINALLY GRADUATES
TO VERSION 1.0 AND BEYOND.
SO A NEW REQUIREMENT FROM US IS
THAT IF THE TRIAL HAS BEEN
PRIORITIZED AND REGISTRATIONAL
AND PRIORITIZES NEEDING A TRIAL
MASTER FILE THEN THAT HAS TO BE
ESTABLISHED BEFORE THE TRIAL CAN
BEGIN.
AND AT THIS POINT IS WHEN THE
PROTOCOL IS SUBMITTED TO THE FDA
AND TO THE SITES TO WORK ON AS
WELL.
THEN OUR MOST HEAVY STATE OF
INVOLVEME
INVOLVEMENT IS INSPECTION
PREPAREDNESS WHICH IS AN
ALL-HANDS ON DECK SITUATION IF A
TRIAL OR EVEN A SITE COMES UP
FOR REGULATORY INSPECTION.
SO I WILL SAY THIS WAS THE
SIMPLICITY I CAN MAKE THIS
SLIDE.
SIMPLEST I CAN MAKE THE SLIDE.
THE PROCESS HAS BECOME MORE AND
MORE COMPLICATED OVER THE LAST
SEVERAL YEARS AS THE REGULATORY
REQUIREMENTS HAVE EVOLVED.
SO FOR THOSE OF YOU WHO HAVE
NEVER HEARD OF A TRIAL MASTER
FILE, IT'S A COLLECTION OF
ESSENTIAL DOCUMENTS FOR THE
TRIAL THE REGULATORS USE IT AS A
WAY TO RECONSTRUCT WHAT YOU'VE
DONE LIKE A LAB NOTEBOOK AND FOR
A SINGLE TRIAL CONSISTS OF
THOUSAND OF DOCUMENTS.
IT SOUNDS SIMPLE LIKE YOU'RE
JUST FILING DUALITIES AWAY AND
LIKE EVERYTHING WE LAY OUR HANDS
ON IT'S VERY COMPLEX.
SO THAT IS AN EMA REQUIREMENT
AND THE REASON WE CARE IS
BECAUSE MOST OF OUR PRODUCTS AT
THIS POINT WE DO GLOBAL RESEARCH
SO WE DO FALL UNDER THE
REGULATIONS AND MOST OF OUR
PRODUCTS WILL BE MOST WANT TO
USE IT INTERNATIONALLY
ESPECIALLY IN THE HIV WORLD.
THEY'LL SEEK EME APPROVAL.
I'LL TALK MORE HOW WE DO THIS.
WE COLLABORATE HEAVILY ACROSS
THE DIVISION AND HAVE
ESTABLISHED GOOD PARTNERSHIPS
AND WE WORK WITH OUR SISTER
OFFICES.
REALLY, OUR OFFICE CONSISTS OF A
LITTLE OVER 30 PEOPLE ABOUT 32
PEOPLE AND SPARED YOU FROM THE
ORGANIZATIONAL SLIDE BECAUSE IT
WAS TOO MESSY BUT I DO WANT TO
EMPHASIZE THIS TYPE OF WORK
REQUIRES A TYPE OF PERSON WHO IS
WILLING AND ABLE TO BE
COLLABORATIVE.
THE REGULATORY SUPPORT CONTRACT
IS PART OF WHAT EXTENDS OUR
STAFFING ESSENTIALLY.
SO WE CAN GET THE WORK DONE FOR
A LARGE CLINICAL RESEARCH
PORTFOLIO.
SO THIS IS A FULL SERVICE
REGULATORY SUPPORT CONTRACT THAT
PROVIDES COMPREHENSIVE
REGULATORY SUPPORT SERVICES FOR
ALL DADE SUPPORTED NETWORK AND
SOME NON-NETWORK TRIALS.
THAT SUPPORT ENABLES US TO MEET
OUR REQUIREMENTS AND CARRY OUT
THE CORE MISSION OF THE OFFICE
WHICH IS TO SUPPORT CLINICAL
TRIALS RESEARCH.
I WON'T GO THROUGH ALL OF THIS
SINCE IT IS THE END OF THE DAY
BUT THEY PROVIDE A SIGNIFICANT
AMOUNT OF SUPPORT WITH RESPECT
TO EACH TEAM AND EACH BRANCH
WITHIN OPCRO.
THEY PROVIDI -- PROVIDE IND
SUPPORT AND TO OUR CLINICAL
TRIALS AGREEMENTS TEAM WHICH IS
REALLY ONLY FOUR PEOPLE.
OUR PROTOCOL REGISTRATION PEOPLE
WHICH IS TWO.
OUR SAFETY REPORTING TEAM AND
THEY OVERSEE THE REPORTING
SYSTEM AND DO THE INITIAL TRIAGE
OF EVENTS FOR THE MEDICAL
OFFICERS TO REVIEW.
THEY ALSO SUPPORT FOR
INSPECTION-RELATED ACTIVITIES
AND THE MASTER TRIAL AND WE HAVE
THIS INTERESTING AND USEFUL
HABIT OF INSPECTING OURSELVES
OCCASIONALLY AND WHEN WE KNOW A
PRODUCT IS BEING SUBMITTED BY
THE MANUFACTURER WE HAVE
INSPECTIONS AS OURSELVES AS A
SPONSOR AND SOME OF THE SITES WE
THINK ARE MOST LIKELY TO BE
INSPECTED AND USUALLY THAT
GENERATES AN INSPECTION WORKING
GROUP AND THEY ADDRESS REMAINING
ISSUES IT WHICH HAVE BEEN
SUCCESSFUL.
THE OTHER THING THE RC HAS DONE
OVER THE LAST TWO YEARS IS
SUPPORT FOR COVID-19 WITH
RESPECT TO PROGRAM MANAGEMENT OR
ACTIV 2 AND HELP WITH THE
CORRELATES WORK BY DOING
SUBMISSIONS FOR THE DRUG MASTER
TRIALS AND THE VACCINE INDs.
I WANTED TO TALK A LITTLE BIT
ABOUT ACTIV 2 BECAUSE IT'S BEEN
AN INCREDIBLY DEMANDING TIME AS
IT HAS FOR US AND FOR EVERYONE
ACROSS THE DIVISION AND MOST
PEOPLE ACROSS THE WORLD.
THIS HAS BEEN DIFFERENT FROM
OTHER TRIALS WHERE WE
SUBCONTRACTED AND CONTRACTED
WHAT WE USUALLY DELEGATE TO THE
NETWORKS IN TERMS OF CONDUCT OF
THE TRIAL TO A CONTRACTOR.
THE MAIN TRIAL WELL ALL ARE
ADAPTIVE TREATMENT TRIALS FOR
PATIENTS WITH COVID-19.
THEY HAVE OVERSIGHT OF THE
TRIALS AND FUNDED UNDER THE SS
COF CONTRACT WHICH I WILL TALK
ABOUT AND SUPPORT SERVICES
CONTRACT.
SORRY, I DIDN'T SPELL THAT OUT
WHICH IS HELD BY PHARMACEUTICAL
DEVELOPMENT A PPD FULL SERVICE
CONTRACT ORGANIZATION.
THEY OVERSEE MANY OPERATIONAL
ASPECTS.
SO WHAT THAT LOOKS LIKE AND THE
WAY IN WHICH THAT IS DIFFERENT
IS DAIDS STILL THE REGULATORY
SPONSOR.
BUT THE NETWORK IS LESS INVOLVED
IN FACT THE LLC AND THE SDMC ARE
NOT REALLY INVOLVED AT ALL.
IT HAS MINIMAL INVOLVEMENT IN
TERMS OF HELPING WITH THE
LABORATORY DATA MANAGEMENT
SYSTEM.
THE NETWORK AND PROTOCOL TEAM
ARE STILL THE NETWORK AND THE
NETWORK IS INVOLVED IN THE TRIAL
AND THE LABS.
THE VIROLOGY IS PROCESSED IN
ACTG LABS AND NOT PPD BUT THE
GENERAL LABS ARE ALL PROCESSED
BY ONE OF PPD'S LABS.
A CENTRAL LABORATORY.
AND OUR SITES AND THERE ARE ALSO
A HOST OF OTHER SITES THAT HAVE
BEEN RECRUITED AND ARE
CONTRACTED TO PPD DIRECTLY.
AND PROVIDE OVERSIGHT IN A WAY
IN WHICH WE HAVE NOT BEFORE.
I WOULD SAY THIS HAS INVOLVED
EVERY LEVEL OF EVERY PROGRAM AND
OFFICE THAT IS INVOLVED WITH
THIS TRIAL.
PETER KIM AND PAYTON AND I MEET
REGULARLY AND INVOLVED IN A
PROTOCOL LEVEL WHICH IS HONESTLY
NOT WHAT WE USUALLY DO.
WE PROVIDE OVERSIGHT IN
PHARMACEUTICAL MANAGEMENT AND
MONITORING, SAFETY, DATA
MANAGEMENT AND HUMAN SUBJECTS
PROTECTION.
IT'S A COMPLEX TRIAL AND THE
FIRST PLATFORM TRIAL THAT DAIDS
HAS DONE AND IT HAS BEEN QUITE
AN EDUCATIONAL EXPERIENCE AND I
WOULD SAY I'VE BEEN TOUCHED AND
PLEASED BY THE WAY OUR STAFF HAS
RESPONDED.
THEY HAVE RESPONDED
MAGNIFICENTLY.
THEY HAVE RISEN TO THE OCCASION.
EVERYONE HAS BEEN WORKING PRETTY
MUCH FOR THE PAST TWO YEARS AND
AT THE MOMENT THERE'S NOT REALLY
AN END IN SITE.
THE ACTIV 2 TRIAL IS UNDER THE
HIV SUPPORT SERVICES CONTRACT
AND IT ALOUD -- ALLOWED US TO
PIVOT IN A SIGNIFICANT WAY TO
COVID-19 AND WE USED THE
CONTRACT FOR OTHER OUTBREAKS
INCLUDING ZIKA AND OTHERS.
IT'S A FULL SERVICE CONTRACT
THAT PROVIDES A WIDE RANGE OF
CLINICAL AND LABORATORY AND
TRAINING RELATED SERVICES IN
SUPPORT OF OUR TRIALS.
IT FACILITATES AN AGILE RESPONSE
INCLUDING PUBLIC HEALTH
EMERGENCIES AND PROVIDES AD HOC
AND RECURRING SERVICES TO ENSURE
DAIDS NEEDS SPONSOR OBLIGATIONS
AND PROVIDE AS A BROAD RANGE OF
GAP FILLING AND ROUTINE CLINICAL
LABORATORY TRAINING AND OTHER
RELATED RESEARCH SUPPORT
SERVICES FOR DAIDS.
SO THIS IS AN EXAMPLE OF THE
URGENT WORK WE'VE IMPLEMENTED
INCLUDES ACTIV 2.
I MENTIONED ZIKA SUPPORT BEFORE.
SOME OF THE GAP FILLING WORK HAS
BEEN THIS OVER 30 WORK
ASSIGNMENTS ESSENTIALLY
SUBCONTRACTS THAT HAVE A RANGE
OF CONSULTANTS AND PROVIDE
PRE-IND SUPPORT AND DEVELOPMENT
AND GLP LAB AUDITS.
A HUGE PROGRAM.
WE'VE CONDUCTED 150 GCL AUDITS
AND PROVIDED IN-COUNTRY
APPLICANT REPRESENTATION FOR
DAIDS SPONSORED TRIALS.
WE ALSO PROVIDED CLINICAL SITE
SUPPORT AND AD HOC TECHNOLOGY
AND MANAGEMENT SUPPORT AND AD
HOC TRAINING AND IN-PERSON
TRAINING WHEN THAT WAS A THING
WHEN NECESSARY.
THAT IS IT.
SO THANK YOU FOR YOUR ATTENTION.
I REALIZE A FEW PEOPLE HAVE HAD
TO DROP OFF BUT IF THERE'S ANY
QUESTION
QUESTIONS.
>> THANK YOU.
IMPORTANT WORK TO ENSURE THE
QUALITY AND SAFETY OF THE DATA
AND EVIDENCE AND COULD NOT BE
MORE IMPORTANT NOW FOR US TO ALL
UNDERSTAND HOW MUCH WE CAN TRUST
THE DATA THAT HAS COME OUT OF
THE STUDIES AND IT'S CRITICAL.
AT ONE POINT YOU SAID IT SOUNDS
SIMPLE AND I THOUGHT, NO, NONE
OF US THINK IT'S SIMPLE IS THANK
YOU.
THANKS TO EVERYONE.
I'M GOING HAND IT TO CARL WHO I
THINK HAS A QUICK ONE-MINUTE --
YES.
THANKS TO EVERYONE.
>> I NEED THE LIAISONS TO RAISE
THEIR HANDS.
THANK YOU.
THAT WAS IT.
>> THANK YOU.
THANKS TO EVERYONE.
GREAT PRESENTATIONS.
GREAT WORK.
WE WILL NOT BE IN PERSON IN
JUNE.
WE HOPEFULLY WILL BE IN PERSON
IN SEPTEMBER.
TAKE CARE, STAY WELL AND WE'LL
STAY IN TOUCH.
THANKS TO EVERYONE.