>> HELLO, AND WELCOME, EVERYONE.
I'M ELAINE ABRAMS, THE CHAIR OF
THIS COMMITTEE.
I'D LIKE TO WELCOME YOU TO THE Y
COMMITTEE MEETING.
WE HAVE A PACKED AGENDA.
I'M VERY PLEASED TO SEE
EVERYBODY HERE, AND THOSE FOLKS
WHO ARE JOINING US ON ZOOM.
WE'LL START BY DISCUSSING THE
MINUTES FROM THE JANUARY 30TH
MEETING, WHICH CAN BE FOUND IN
THE ELECTRONIC COUNCIL BOOK, AND
ARE THERE ANY COMMENTS ON THE
MINUTES?
IF NOT, COULD I HAVE A MOVE TO
APPROVE THE MINUTES?
AND SECOND?
ALL IN FAVOR?
OKAY, FANTASTIC.
SO I WILL NOW TURN THE MEETING
OVER TO CARL DIEFFENBACH, WHO
WILL PROVIDE THE DIRECTOR'S
REPORT.
>> THANK YOU, ELAINE.
IT REALLY IS A PLEASURE TO SEE
ALL OF YOU IN ONE PLACE AND NOT
IN A LITTLE 2 BY 2 ON A SCREEN.
AS DIANE SAID, IT'S REALLY GREAT
TO SEE PEOPLE IN THREE
DIMENSIONS.
SO I'D LIKE TO START BY
WELCOMING YOU, BUT ALSO TO
INTRODUCE YOU TO THE NEW MEMBERS
OF OUR COMMITTEE.
SO I'VE GOT A WHOLE SERIES OF
PEOPLE AND OTHER APPOINTMENTS
HERE AT THE NIH.
SO FIRST UP IS DR. GRACE
ALDROVANDI, WHO IS A
PHYSICIAN-SCIENTIST AND CHIEF OF
THE DIVISION OF INFECTIOUS
DISEASES AT THE UCLA MATTEL
CHILDREN'S HOSPITAL AND
PROFESSOR OF PEDIATRICS AT THE
GEFFEN SCHOOL OF MEDICINE AT
UCLA.
SHE CURRENTLY SERVES AS THE P.I.
OF THE LABORATORY CENTERS FOR
THE ACTG AND THE IMPACT
NETWORKS.
HER RESEARCH INTERESTS INCLUDE
PATHOGENESIS OF HIV IN WOMEN AND
CHILDREN AND EFFECTS OF BREAST
MILK IN THE MICROBIOME ON INFANT
HEALTH AND LABORATORY
DIAGNOSTICS.
DR. SEEMA SHAH, ACTUALLY SEEMA
SHAH, J.D., IS THE ASSOCIATE
PROFESSOR IN PEDIATRICS AT
NORTHWESTERN UNIVERSITY AND
FOUNDER'S BOARD PROFESSOR OF
MEDICAL ETHICS AT THE LURIE
CHILDREN'S HOSPITAL.
SHE'S ALSO THE DIRECTOR OF
RESEARCH ETHICS AND LEADS
PEDIATRIC RESEARCH ETHICS
PROGRAMS AT THE HOSPITAL.
SHE'S ALSO A FORMER MEMBER OF OF
THE BIOETHICS PROGRAM HERE AT
THE NIH, AND IT IS REALLY A
PLEASURE TO HAVE SEEMA BACK
SERVING ON ONE OF OUR
COMMITTEES.
WE WORK SO WELL TOGETHER WITH
HER AND THE GROUP IN THE PAST.
NEXT IS KELLY GEBO, PROFESSOR OF
MEDICINE AND EPIDEMIOLOGY AT THE
JOHNS HOPKINS SCHOOL OF
MEDICINE, WHERE SHE COMPLETED
HER MEDICAL DEGREES AND INTERNAL
MEDICINE RESIDENCY AND
FELLOWSHIP.
SHE IS A ROBERT WOOD JOHNSON
CLINICAL SCHOLAR, AND RECEIVED
AN M.P.H. FROM BLOOMBERG.
SO THAT, WE HAVE IN COMMON FOR
B,WE'RE BOTH GRADUATES OF
BLOOMBERG.
HE RESEARCH IS FOCUSED ON
COVID-19, HIV AND OTHER
INFECTIOUS DISEASES.
SHE'S SERVED AS A MENTOR OR
CO-MENTOR ON 10 JUNIOR
INVESTIGATOR TRAINING AWARDS.
NEXT IS TIM HENRICH.
TIM HENRICH IS A PHYSICIAN
SCIENTIST AND I.D. CLINICIAN,
PROFESSOR OF MEDICINE NE
DIVISION OF EXPERIMENTAL
MEDICINE AT UCSF, WHERE HE RUNS
A TRANSLATIONAL INFECTIOUS
DISEASE RESEARCH PROGRAM
FOCUSING ON HIV, SARS-COV-2, AND
HUMAN HERPES VIRUSES.
DR. HENRICH IS ALSO INVOLVED IN
THE DESIGN AND IMPLEMENTATION OF
NOVEL NANO AND MICRO
TECHNOLOGIES AND PET-BASED
IMAGING APPROACHES TO
CHARACTERIZE RESERVOIRS.
MOST RECENTLY, DR. HENRICH HAS
STUDIED LONG COVID, AND THE
OTHER IMMUNOLOGICAL SEQUELAE OF
SARS-COV-2 INFECTION.
NEXT IS DR. RAPHI LANDOVITZ,
PROFESSOR OF MEDICINE AND
INTERIM CHIEF IN THE DIVISION OF
INFECTIOUS DISEASES AT THE
GEFFEN SCHOOL OF MEDICINE AT
UCLA.
HE'S ALSO BEEN A MAJOR PLAYER IN
THE HPTN AND SERVED AS THE
CO-DIRECTOR, THE CO-CHAIR OF THE
O83 TRIAL.
HE'S PLAYED A MAJOR ROLE IN THE
CHIPTS CENTER AND HIS RESEARCH
CONTINUES TO FOCUS ON
OPTIMIZATION AND USE OF
ANTIRETROVIRALS FOR TREATMENT
AND PREVENTION.
NEXT IS LISHOMWA NDHLOVU,
PROFESSOR OF IMMUNOLOGY IN
MEDICINE, DIVISION OF INFECTIOUS
DISEASES, SECONDARY APPOINTMENT
AT THE RESEARCH INSTITUTE AT
WEILL CORNELL.
HIS TEAM COMBINES IMMUNOLOGY AND
VIROLOGY AND EPIGENETIC METHODS,
EXPLORING MOLECULAR MECHANISMS
OF HIV PATHOGENESIS AND
PERSISTENCE THROUGH PRE-CLINICAL
AND CLINICAL INVESTIGATIONS.
NEXT IS LINDA KOENIG, WHO'S OUR
EX-OFFICIO ALTERNATE FROM THE
CDC, HERE FOR THIS MEETING.
AND I'D LIKE TO ANNOUNCE THAT ON
THE 8TH OF APRIL, FRANCISCO RUIZ
WAS NAMED THE DIRECTOR OF OFFICE
OF NATIONAL AIDS POLICY, AND HIS
APPOINTMENT IS REALLY IMPORTANT
FOR US AS A LEADER TO HELP US
BRING ABOUT THE EVOLUTION OF THE
EHE PROGRAM AND CONTINUE TO HELP
US GET TO A PLACE WHERE WE'RE
FULLY IMPLEMENTING THE NATIONAL
HIV/AIDS STRATEGY AS WELL AS THE
EHE PROGRAM.
SO HE WAS AT CDC BEFORE JOINING
ONAP.
THIS WAS TALKED ABOUT THIS
MORNING BUT I REALLY WANT TO
SPEND JUST A MOMENT MORE TALKING
ABOUT THE NIAID LANGUAGE GUIDE
AND HOW WE FORESEE IT BEING
USED.
SO WHAT WE WILL ENVISION IS
THERE WILL BE A SERIES OF SLIDES
THAT WHEN NIAID OR DAIDS
SPONSORS A MEETING, WHETHER IT'S
A NETWORK OR GROUP MEETING, THAT
THE SLIDE WILL BE USED TO START
THE MEETING, SETTING THE STAGE
FOR THE IMPORTANCE OF THE NEED
TO END THE USE OF STIGMATIZING
LANGUAGE.
TO PUT THAT IN THE POSITIVE, TO
SAY WE'RE GOING TO FOCUS ON
LANGUAGE THAT IS PERSON-CENTERED
AND PERSON-FIRST.
THIS IS AN AREA THAT WE'VE BEEN
EMPHASIZING SINCE 2017, WHEN WE
PUBLISHED OUR FIRST VERSION OF
THIS LANGUAGE GUIDE, AND THE URL
THERE IS THE LINK TO THE GUIDE.
SO THIS IS WHAT IT LOOKS LIKE
WHEN YOU GO TO THE WEBSITE.
THE BIG BLUE BOX ALLOWS YOU TO
DOWNLOAD THE LANGUAGE GUIDE, AND
AT THE SAME TIME, YOU CAN SEE
UNDER THERE ARE SUPPORTING
MATERIALS.
AND THESE REPRESENT SLIDES AND
TEMPLATES THAT, DEPENDING ON
YOUR USE AND WHETHER IT'S A
MEETING INVITATION TORE A
SPEAKER'S INVITATION, OR A
SPECIFIC TEMPLATE INTRODUCTORY
SLIDE, IT ALLOWS YOU AS A
MEETING ORGANIZER TO TAILOR YOUR
NEEDS SO THAT YOU HAVE THE
ABILITY TO USE THIS LANGUAGE
GUIDE AS WE GO FORWARD WITH OUR
DAIDS-SPECIFIC MEETINGS.
I'LL JUST SPEND A MOMENT GOING
OVER THE BUDGET.
WHEN WE MET IN JANUARY, WE STILL
DIDN'T HAVE A BUDGET.
WE WERE STILL UNDER THE -- WHERE
THERE WAS STILL A POSSIBILITY OF
A FAIRLY SUBSTANTIAL CUT.
COULD YOU GO BACK A SLIDE?
YOU'RE GOING JUST A LITTLE FAST
FOR ME.
BACK ONE.
THANK YOU.
THAT'S THE SLIDE.
SO WHAT WE ENDED UP HAVING IS
ESSENTIALLY A FLAT BUDGET FOR
THE YEAR, WHICH WAS THE BEST BAD
OUTCOME WE COULD ASK FOR, AND
WE'LL SEE WHAT HAPPENS NEXT
YEAR.
WHAT WE HAVE SEEN, THOUGH, IS,
BECAUSE OF THE FINANCIAL
MANAGEMENT PLAN, WE HAVE AN
ESTABLISHED PAYLINE FOR PIs OF
TENTH PERCENTILE FOR NEW PIs,
A 14TH PERCENTILE.
NONCOMPETING GRANTS ARE BEING
AWARDED AT 100%.
COMPETING INVESTIGATOR-INITIATED
AWARDS ARE BEING RELEASED AT THE
90 PERCENT LEVEL, AND THERE'S NO
ADJUSTMENT TO Ks, Ts AND
Fs OR SBIR GRANTS.
RESEARCH INITIATIVES HAVE BEEN
CUT BY UP TO 20%.
THIS GIVES US A PROPOSED SUCCESS
RATE AT THE END OF THE DAY OF
BETWEEN 16 AND 20%.
THE PRESIDENT'S BUDGET FOR 2025
HAS BEEN RELEASED.
IT HAS A SMALL INCREASE PROPOSED
OF $19 MILLION OVER 2024.
KEEPING IN MIND, HOWEVER, THAT
THE GROUPS IN CONGRESS ARE WHO
WERE PROPOSING -- OKAY.
I THINK THE EARTHQUAKE OR
SOMETHING IS MAKING THE SLIDES
CHANGE.
ARE STILL PROPOSING FAIRLY
SIGNIFICANT CUTS, SO WE'RE IN
FOR ANOTHER ROUND OF ACTIVITIES
GOING INTO -- SO IT WILL BE
INTERESTING TO SEE WHERE WE ARE
WHEN WE COME BACK IN SEPTEMBER.
AND THEN WHEN WE GET TOGETHER IN
JANUARY WITH ANY LUCK AT ALL,
WE'LL HAVE A BUDGET HOPEFULLY BY
JANUARY.
SO THAT'S WHERE WE ARE WITH THE
FY 25 PRESIDENT'S BUDGET AT A
.3% INCREASE.
SO THERE'S A COUPLE OF
SCIENTIFIC AND PROGRAM UPDATES I
WANT TO TALK ABOUT.
NOT THE TRADITIONAL
SCIENCE-BASED ONES WE'VE DONE IN
THE PAST.
AGAIN, THE STRATEGIC PLAN THAT
GENIE TALKED ABOUT TODAY IS
REALLY AN IMPORTANT PART OF
WHERE WE ARE FOCUSING.
THIS TIES IN VERY NICELY WITH
WHERE WE AS A DIVISION ARE IN
THE MIDDLE OF -- OR BEGINNING
THE PROCESS OF LOOKING AT THE
SIZE, SCOPE AND FUTURE DIRECTION
OF OUR CLINICAL TRIALS
ENTERPRISE, BECAUSE AS WE ARE
MOVING THAT FORWARD, AND LOOKING
AT FIRST 2027 AND THEN 2034,
WHICH WOULD BE THE NEXT MAJOR
RENEWAL, WE NEED TO KEEP IN MIND
THAT THIS IS GOING TO BE TIED TO
THE NIAID STRATEGIC PLAN.
SO WHERE WE ARE RIGHT NOW IS
WE'VE HAD THE RFI CLOSED, WE ARE
GOING TO SPEND A SIGNIFICANT
AMOUNT OF TIME GOING THROUGH THE
INPUT THAT WE RECEIVE FROM THE
COMMUNITY WITH THE IDEA, THEN,
WE WILL UPDATE YOU IN SEPTEMBER,
AND THEN AGAIN, IN JANUARY ABOUT
PROGRESS NOT JUST ON THE
STRATEGIC PLAN, BUT ALSO ON OUR
PROGRESS TOWARD DEFINING THE
SIZE, SCOPE AND FUTURE
DIRECTIONS OF THE CLINICAL
TRIALS ENTERPRISE.
WE WILL NOT BE PUBLISHING
ANYTHING IN FISCAL YEAR '25 ON
THE NETWORKS.
WE WILL -- IN 2025, WE'LL BE
GOING INTO A RUN SILENT, RUN
DEEP AFTER THE COUNCIL MEETING
IN JANUARY AND WRITING THE
FUNDING OPPORTUNITY
ANNOUNCEMENTS, WHICH WILL BE
RELEASED AND DISCUSSED AND DEALT
WITH AS WE GO FORWARD.
TO PUT THAT IN CONTEXT.
HERE'S THE PROPOSED
ORGANIZATIONAL STRUCTURE FOR OUR
STRATEGIC PLAN, STARTING WITH
THE VISION, MISSION, PRIORITIES,
OBJECTIVES AND FOCUS AREAS.
AS JEANIE SAID THIS MORNING, YOU
MAY HAVE MISSED IT, BUT IT WAS
KIND OF AN OFF-HAND REMARK, THIS
STRUCTURE IS IMPOSED UPON US BY
THE NIH O.D. THAT WE HAVE TO
FOLLOW THIS KIND OF STRUCTURE.
THE IDEA IS THAT ALL STRATEGIC
PLANS WILL HAVE A SIMILAR SHAPE.
THE PYRAMID, ACROSS THE
INSTITUTES.
AND AS I WAS SAYING, WE ARE IN
THE MIDDLE OF THE NETWORK
RESCOPING, THE NETWORK
COMPETITION.
TO DATE, WE'VE HAD ALL OF THE
NETWORKS COME IN AND PRESENT
THEIR PROGRESS TO DATE, WHAT
THEY ARE SEEKING TO ACHIEVE IN
THE NEXT 3 1/2 YEARS, AND THEIR
VISION THEN FOR THE NEXT SEVEN.
THAT HAS NOW BEEN COMPLETED.
WE'VE HAD OUR FIRST WEBINAR THAT
WAS JUST THIS PAST WEEK.
WE HAD OVER 250 MEMBERS OF
COMMUNITY AND STAKEHOLDERS ON
THAT CALL.
IT WAS REALLY INSIGHTFUL TO HEAR
THE QUESTIONS AND TO GET THE
FEEDBACK.
WE ARE GOING TO HAVE ADDITIONAL
CALLS.
CAN WE GO BACK A SLIDE, PLEASE?
I REALIZE YOU WANT TO SPEED ME
UP BUT -- WE ARE GOING TO HAVE
ADDITIONAL EVENT THROUGHS THROUE
SUMMER.
WHEN WE GET TO THE FALL MEETING,
WE WILL HAVE A DRAFT PLAN AS A
STRAW DOG FOR YOU AS A COMMITTEE
TO GET INPUT INTO BASED ON YOUR
FEEDBACK AND OTHER CONSULTATIONS
THAT WE WILL HAVE THROUGH THE
FALL AND INTO THE WINTER.
WE WILL COME BACK TO YOU AS A
COMMITTEE IN JANUARY OF 2025
WITH A FINAL VIEW OF WHERE WE
THINK WE HAVE ACHIEVED A DEGREE
OF COVERAGE OF GETTING THE BEST
INPUT WE CAN AND ALSO BEING SURE
THAT WE'RE SOLICITING THE BEST
SCIENCE AS WE GO FORWARD.
WE WILL WRITE THE FOAs, AGAIN
PUBLISHING THEM IN 2026.
WE WILL DO THE SAME SORT OF
THING THAT WE DID BEFORE, THAT
WE'LL HAVE STAGGERED RELEASE OF
SITE FOAs AND LEADERSHIP GROUP
FFOAs WITH APPLICATIONS COMING
BACK TO THE COUNCIL FOR FINAL
REVIEW IN SEPTEMBER OF 2027,
WITH A RENEWAL START DATE OF
DECEMBER 2027, WHICH WILL BE ON
SCHEDULE.
SO THESE ARE OUR FUTURE
MEETINGS.
KEEP IN MIND THAT FOR THE
FORESEEABLE FUTURE, ALL THE
JANUARY COUNCIL MEETINGS WILL
REMAIN VIRTUAL.
WE'VE HAD SUCH GOOD LUCK WITH
SNOWSTORMS IN PREVIOUS YEARS
THAT THERE ALWAYS SEEMS TO BE A
MASSIVE SNOWSTORM THAT MADE IT
SO WE HAD TO GO VIRTUAL, SO WHY
NOT JUST GO WITH THE INEVITABLE
AND AS YOU CAN SEE JANUARY 26,
YOU CAN THEN CARRY THAT INTO THE
FUTURE, BUT SEPTEMBER AND JUNE
MEETINGS WILL BE HYBRID AND IN
PERSON LIKE THIS ONE.
AND WITH THAT, I WILL CLOSE AND
OPEN THE FLOOR TO QUESTIONS.
SO THANK YOU.
YOU CAN TAKE THE SLIDES DOWN
NOW.
IT'S OPEN FOR QUESTIONS.
>> I THINK IT WAS VERY CLEAR.
THANK YOU.
>> ALL RIGHT.
>> SO WE'LL MOVE ON NOW TO
DR. ANNE NEILAN TO PROVIDE THE
OFFICE OF AIDS RESEARCH ADVISORY
COUNCIL BRIEFING.
>> GOOD AFTERNOON, EVERYONE.
I'M ANNE NEILAN.
HAPPY TO BE THE OARAC LIAISON TO
ARAC.
THANKS FOR THE OPPORTUNITY TO
PRESENT TODAY ON BEHALF OF OARAC
AND GIVE A DEBRIEF AND SOME OF
THE HIGHLIGHTS OF THE LAST OARAC
MEETING WHICH WAS THE 65TH
MEETING AND SHARE A FEW OTHER
OAR-RELATED UPDATES.
SO FIRST, LEADERSHIP
TRANSITIONS.
LAST YEAR DR. BILL KAPOGIA NNIS
LEFT FOR A POSITION AT BARDA
WITHIN THE HHS ADMINISTRATION
FOR STRATEGIC PREPAREDNESS AND
RESPONSE.
AND THEN EFFECTIVE
DECEMBER 17TH, 2023, DR. DIANA
FINZI TOOK THE ROLE AS ACTING
DIRECTOR WHILE THE SEARCH
CONCLUDES.
DIRECTOR OF THE BASIC SCIENCES
PROGRAM IN THE DIVISION OF AIDS
HERE AT NIAID.
DR. FINZI IS AN IMMUNOLOGIST BY
TRAINING AND HAS BEEN AT NIAID
FOR OVER 20 YEARS.
ALSO REAR ADMIRAL TIMOTHY HOLTZ
RETIRED FROM THE U.S. PUBLIC
HEALTH SERVICE AND FROM HIS ROLE
AS OAR DEPUTY DIRECTOR ON
MARCH 31ST, AND WHILE THE SEARCH
FOR A PERMANENT DEP DEDIRECTOR
IS ALSO ONGOING, CAPTAIN MARY
GLENSHAW IS SERVING AS ACTING
DEPUTY DIRECTOR AND AS THE
DESIGNATED FEDERAL OFFICIAL FOR
OARAC, A POSITION ALSO FORMERLY
HELD BY REAR ADMIRAL HOLTZ.
THE 65TH OARAC MEETING WAS HELD
VIRTUALLY ON FEBRUARY 22ND, AND
THAT MEETING AGENDA FEATURED A
REPORT FROM DR. FINZI, UPDATES
ON OAR'S PLANS FOR THE NEXT NIH
STRATEGIC PLAN FOR NIH A HIV AND
HIV-RELATED RESEARCH.
HIGHLIGHTS OF THAT MEETING ALSO
INCLUDED OARAC MEMBERS WHO
COMPLETED THEIR TERMS, AND WERE
PARTICIPATING IN THEIR LAST
MEETING AS OF FEBRUARY 2024.
SO OUTGOING MEMBERS INCLUDED
KATHLEEN COLLINS OF THE
UNIVERSITY OF MICHIGAN, VERONICA
MILLER OF THE UNIVERSITY OF
CALIFORNIA, BERKELEY SCHOOL OF
PUBLIC HEALTH, RICARDO RIVERO,
UNIVERSITY OF ILLINOIS AT
CHICAGO COLLEGE OF MEDICINE, AND
JOHN SLEASMAN, FROM DUKE
UNIVERSITY SCHOOL OF MEDICINE.
DR. FINZI ALSO WELCOMED THE FIVE
INCOMING AD HOC MEMBERS ON THE
RIGHT SOON TO BE FULL VOTING
MEMBERS.
COURTNEY FLETCHER OF THE
UNIVERSITY OF NEBRASKA MEDICAL
CENTER, SONIA FLORES, ANNA MARIA
MANDALAKAS, DIANE SANTA MARIA
AND SARA SAWYER FROM UNIVERSITY
OF COLORADO.
ALSO AT THAT MEETING DR. IVY
TURNBULL WAS OWE FENGSLY
RECOGNIZED AS OARAC CHAIRPERSON.
THIS SLIDE HIGHLIGHT TWO OAR
ENGAGEMENTS THAT OCCURRED LATE
IN 2023 AND THOSE WERE
NOVEMBER 2023 ON THE LEFT THERE,
THE OAR SIGNATURE PROGRAM ON
TECHNOLOGY ADVANCES FOR HIV
RESEARCH.
COLLABORATED WITH OAR'S IC
PARTNERS TO CONVENE A TWO-DAY
COMMUNITY-ORIENTED WORKSHOP ON
ADVANCING HIV TESTING TECHNOLOGY
DEVELOPMENT.
HAROLD PHILLIPS, WHO'S GOT A
QUOTE THERE ON THE LEFT IN
ITALICS IN HIS ROLE AS DIRECTOR
OF THE WHITE HOUSE OFFICE OF
NATIONAL AIDS POLICY, WAS
FEATURED SPEAKER AT THIS TIMELY
WORKSHOP.
THEN ON THE RIGHT, DECEMBER 1ST,
2023 WAS THE 35TH WORLD AIDS
DAY, AND OAR LED THE NIH
OBSERVANCE WITH A VIRTUAL EVENT
ENTITLED ACHIEVING EXCELLENCE
AND EQUITY IN HIV RESEARCH.
IF YOU'RE INTERESTED IN MORE
INFORMATION ABOUT THESE EVENTS,
THERE'S THE QR CODE ON THE SLIDE
OR ON THE WEBSITE.
SO THE REST OF THE MEETING
FOCUSED ON THE DEVELOPMENT OF
THE NEXT STRATEGIC PLAN FOR HIV
AND HIV-RELATED RESEARCH WHICH
IS GOING TO COVER FISCAL YEARS
2026 AND 2030.
THE OFFICE IS LOOKING TO -- OAR
IS LOOKING TO OARAC AND THE
BROADER COMMUNITY FOR INPUT AS
IT WORKS TO DETERMINE HIV
RESEARCH PRIORITIES, GAPS AND
AREAS OF FOCUS.
DR. FINZI NOTED AT THAT MEETING
THE OPPORTUNITIES AND THE
CHALLENGES WE FACE GIVEN MAJOR
GAPS THAT PERSIST DESPITE
PROGRESS ALONG THE HIV CURVE
CONTINUUM AND JUST COMMENTED HOW
THIS NIH HIV STRATEGIC PLAN
WHICH PROVIDES FUNDING GUIDANCE
FOR ALL THE DECISIONS IN THE
SETTING OF BUDGETS NOT BEING
LIMITED HAS THE POTENTIAL TO BE
A VERY IMPACTFUL DOCUMENT SO
FOLKS ARE REALLY WORKING HARD ON
THIS.
CAPTAIN GLENSHAW AND DR. RACHEL
ANDERSON WENT OVER THE STUFF
THAT'S ON THIS SLIDE, AND
DESCRIBED THE MANY ACTIVITIES
THEY'VE BEEN UNDERTAKING TO
PREPARE FOR THE DEVELOPMENT OF
THE NEXT FIVE-YEAR PLAN.
O.A.R. PROPOSED A NEW FRAMEWORK
THAT REFLECTS THE HIV RESEARCH
CONTINUUM, AND THIS FRAMEWORK
HERE IS BASED ON THREE
FOUNDATIONAL PRINCIPLES THAT
THEY HIGHLIGHTED.
THE FIRST FOUNDATIONAL PRINCIPLE
IS THAT RESEARCH TO IDENTIFY AND
ADDRESS HIV-RELATED HEALTH
DISPARITIES IS ESSENTIAL TO
ENSURE THAT THE BENEFITS OF
SCIENTIFIC ADVANCES REACH ALL
PEOPLE AND COMMUNITIES AFFECTED
BY HIV.
INCLUDES GROUPS THAT HAVE BEEN
HISTORICALLY UNDERREPRESENTED
AND UNDERSERVED.
THE SECOND PRINCIPLE WAS THAT
RESEARCH MUST ADDRESS THE UNIQUE
NEEDS OF PEOPLE WITH HIV,
INCLUDING THOSE BORN WITH HIV.
AND THIRD, THAT ENGAGEMENT AND
PARTNERSHIP WITH COMMUNITIES
AFFECTED BY HIV ARE ESSENTIAL AT
EVERY STAGE OF RESEARCHMENT THE
PROPOSED FRAMEWORK IS HERE ON
THE SLIDE AND IT INCLUDES THE
THREE BROAD RESEARCH GOALS AND
ONE CAPACITY-BUILDING GOAL THAT
WILL BE LINKED TO OBJECTIVES AND
SO-CALLED TOPICAL PRIORITIES,
AND THIS UPDATED FRAMEWORK
REFLECTS THE INCREASING
INTERSECTION OF HIV PREVENTION,
TREATMENT, COMORBIDITIES AND
RESEARCH ACROSS THE CONTINUUM.
TO DEVELOP THIS FRAMEWORK,
O.A.R. SUBJECT MATTER EXPERTS
CONTRIBUTED ANTITHE NIH HIV/AIDS
EXECUTIVE COMMITTEE WILL BOTH
REMAIN INVOLVED THROUGHOUT THE
STRATEGIC PLANNING PROCESS, AND
INPUT WAS ALSO PROVIDED BY MANY
PEOPLE, INCLUDING RESEARCHERS,
PRACTITIONERS, COMMUNITY
ADVOCATES, FEDERAL PARTNERS AND
THE PUBLIC, MANY OF YOU PROBABLY
SAW THE RFI THAT O.A.R. ISSUED
AND THAT CLOSED IN MARCH AND
THAT RECEIVED MORE THAN 200
RESPONSES FROM A REALLY WIDE
ARRAY OF PEOPLE FILLING THAT
OUT.
O.A.R. IS GOING TO CONTINUE TO
GATHER AND SYNTHESIZE INPUT
THROUGH OCTOBER 2024, AND THEN
WE'LL DRAFT THE PLAN AND
COORDINATE REVIEW WITH THE
OARAC, AND ALSO ACROSS NIH, WITH
THE ULTIMATE GOAL OF LAUNCHING
THE NEW PLAN IN THE SUMMER OF
2025.
I THINK THAT WAS THE BIGGEST
PART OF THE MEETING.
THE MEETING ALSO CLOSED WITH
UPDATES FROM THE ADVISORY
COUNCILS ON THIS SLIDE,
INCLUDING ARAC, AS WELL AS
UPDATES FROM THE HIV CLINICAL
GUIDELINES WORKING GROUPS, WHICH
DEVELOPED THE CLINICAL
GUIDELINES THAT MANY OF US HEERY
LHERERELY ON AS CLINICAL
PRACTITIONERS IN THE U.S. AND
AROUND THE WORLD.
SINCE THE LAST O.A.R. MEETING
THERE HAVE BEEN SOME OTHER
NOTABLE EVENTS TO HIGHLIGHT AND
ADDITIONAL INFORMATION ON EACH
OF THESE IS ALSO AVAILABLE ON
THE O.A.R. WEBSITE.
SO ON THE TOPMOST LEFT, IN
MARCH, O.A.R. AND THE NIH OFFICE
OF RESEARCH ON WOMEN'S HEALTH
CO-SPONSORED A TWO-DAY VIRTUAL
WORKSHOP THAT REVIEWED THE STATE
OF SCIENCE ON HIV IN WOMEN AND
THE GOAL WAS TO INFORM THE
FUTURE RESEARCH AGENDA.
THERE WERE A WIDE ARRAY OF
TOPICS RELATED TO WOMEN, GIRLS
AND GENDER-DIVERSE INDIVIDUALS.
SESSIONS ALSO HIGHLIGHTED
INTERVENTIONS AND CHALLENGES TO
ADVANCING HEALTH EQUITY FOR
WOMEN WITH AND WHO ARE AFFECTED
BY HIV.
IN APRIL ON THE TOP RIGHT, THE
O.A.R. DIRECTOR'S SEMINAR WAS
GIVEN BY DR. SARAH JIANELLA
WEIBEL.
HER TALK, THE LAST GIFT PROGRAM
LESSONS LEARNED FROM ALTRUISTIC
PARTICIPANTS ENROLLED IN HIV
CURE RESEARCH AT THE END OF LIFE
DISCUSSED HER PATH AS AN EARLY
CAREER INVESTIGATOR IN AREAS
SUCH AS HIV RESERVOIR,
TRANSMISSION, COINFECTION AND
ALSO INCLUDED SEX AND
GENDER-RELATED ISSUES.
ALSO IN APRIL, O.A.R. SPONSORED
A HYBRID WORKSHOP DURING THE
INTERNATIONAL WORKSHOP ON HIV
AND WOMEN.
AND THE WORKSHOP PROVIDED AN
OPPORTUNITY FOR PARTNERS TO
DISCUSS ISSUES, GAPS AND OTHER
OPPORTUNITIES AGAIN FOCUSED ON
IMPROVING THE LIVES OF WOMEN.
AND FINALLY, O.A.R. HEARD ITS --
HELD ITS THIRD WORKSHOP FOR
EARLY CAREER INVESTIGATORS IN
HIV.
FURTHERING EFFORTS TO CONTINUE
TO SUPPORT AND PROVIDE KNOWLEDGE
AND RESOURCES AND MENTORING TO
THE UPCOMING GENERATION OF
INVESTIGATORS.
THERE WERE NEARLY 600 ATTENDEES
FROM ACROSS THE WORLD, SO IT WAS
A REALLY WELL-ATTENDED EVENT.
THE O.A.R. WEBSITE POSTS
RECORDINGS OF ALL THE MEETINGS
AND THE NEXT ONE IS GOING TO BE
HELD ON JUNE 20TH, 2024.
IN ADDITION TO THE USUAL
UPDATES, THAT MEETING IS GOING
TO FEATURE A LOT OF TIME SPENT
ON THE PROGRESS ON THE
DEVELOPMENT OF THE NEXT
STRATEGIC PLAN, REMARKS FROM THE
NEW WHITE HOUSE OFFICE OF
NATIONAL AIDS POLICY DIRECTOR,
WHO WE WERE JUST INTRODUCED TO
ON THE SCREEN BY
DR. DIEFFENBACH, FRANCISCO RUIZ,
AND A FOCUS ON ISSUES RELATED TO
HIV CURE AND LONG TERM
SURVIVORSHIP WITH PRESENTATIONS
FROM BOTH INVESTIGATORS AS WELL
AS COMMUNITY PERSPECTIVES.
AND THE MEETING WILL BE
VIDEOCAST.
THANK YOU.
I THINK I CAN ANSWER QUESTIONS.
YES, I CAN ANSWER QUESTIONS.
>> ANY QUESTIONS ONLINE?
>> THANK YOU.
>> THANK YOU VERY MUCH.
OKAY.
WE'RE GOING TO MOVE TO THE
CONCEPT REVIEW AT THIS POINT.
I'LL ASK ALL THE VOTING MEMBERS
TO OPEN YOUR ELECTRONIC COUNCIL
BOOK SO THAT YOU CAN VOTE AT THE
END OF EACH CONCEPT OR, IN THIS
CASE, AT THE END OF A, B AND C,
AND I WILL KEEP REMINDING YOU TO
VOTE REGULARLY THROUGHOUT THE
REST OF THE MEETING.
SO WE'RE GOING TO START WITH A
PRESENTATION BY DIANE LAWRENCE
FROM THE BASIC SCIENCE PROGRAM
ON THE MARTIN DELANEY
COLLABORATORIES FOR HIV CURE
RESEARCH.
ARE YOU GOING TO DO A TAG TEAM
OR TAKE QUESTIONS IN BETWEEN?
QUESTIONS IN BETWEEN.
OKAY.
>> YES.
EXPWH
>> SO WE'LL START WITH YOU AND
THEN HAVE SOME QUESTIONS.
GO AHEAD.
>> THANK YOU VERY MUCH.
AS SHE POINTED OUT, MY NAME IS
DIANE LAWRENCE.
I AM A PROGRAM OFFICER IN THE
BASIC SCIENCE PROGRAM DIVISION
OF AIDS AND I'M HERE WITH MY
COLLEAGUE, TANIA LOMBO, FROM THE
PREVENTION SCIENCES PROGRAM, AND
WE'RE HERE TO REQUEST APPROVAL
FOR A THREE-PART CONCEPT FOR THE
MARTIN DELANEY COLLABORATORIES
FOR HIV CURE RESEARCH.
SO I'LL BE PRESENTING THE FIRST
PART, AND TANIA WILL BE
PRESENTING THE SECOND PART, AND
THEN I'LL BE BACK TO PRESENT THE
FINAL PART OF THE CONCEPT, AND
WE'LL HAVE QUESTIONS AFTER EACH
ONE AND THE OPPORTUNITY TO VOTE,
I GUESS, AFTER EACH ONE.
OKAY.
INDEPENDENTLY?
GREAT.
SO I WILL GO AHEAD AND GET
STARTED.
SO THE FIRST PART IS THE
CONCEPT -- WE'RE CALLING CONCEPT
A, THE ADULT -- WE CALL IT
INFORMALLY, THIS IS THE
LONGEST-RUNNING PART OF THE
COLLABORATORY PROGRAM.
AND THE PURPOSE IS TO ACCELERATE
INNOVATIVE, DYNAMIC AND HIGHLY
COLLABORATIVE RESEARCH SPANNING
BASIC, TRANSLATIONAL AND
CLINICAL BUT NOT INCLUDING
CLINICAL TRIALS THROUGH
PARTNERSHIPS ACROSS ACADEMIA,
INDUSTRY, GOVERNMENT, AND
COMMUNITY.
AND THE OVERALL GOAL IS TO
DEVELOP EFFECTIVE STRATEGIES FOR
ACHIEVING CONTROL OF HIV REBOUND
IN THE ABSENCE OF ANTIRETROVIRAL
TREATMENT OR THE ERADICATION OF
HIV FROM THE BODY.
THIS WILL BE A REISSUE.
THIS WOULD BE OUR FOURTH
ITERATION OF THE PROGRAM.
AND AS IN THE PAST, WE WILL ONLY
ALLOW NEW APPLICATIONS FOR THIS
PROGRAM.
SO WE'RE USING THE
UM1 COOPERATIVE AGREEMENT
MECHANISM, AND WE ANTICIPATE A
FLAT BUDGET FOR THE PROGRAM SO
WE EXPECT TO SUPPORT 7 TO
8 AWARDS BASED ON THE CURRENT
COSTS.
JUST AS AN ESTIMATE.
AND WE HOPE TO CONTINUE
PARTNERING WITH SEVERAL OTHER
NIH INSTITUTES ON THIS
INITIATIVE, AND WE'VE ALSO BEGUN
DISCUSSIONS WITH THE NATIONAL
INSTITUTE ON AGING AS ANOTHER
POTENTIAL PARTNER.
SO WHY DO WE STILL NEED AN HIV
CURE?
AS OF THE LATEST UPDATES FROM UN
AIDS, THERE ARE AN ESTIMATED
39 MILLION PEOPLE WORLDWIDE
LIVING WITH HIV.
DESPITE SUBSTANTIAL GLOBAL
INVESTMENT AND SUCCESSES IN HIV
PREVENTION AND TREATMENT, NEW
DIAGNOSES ARE STILL HAPPENING
AND ARE RISING SHARPLY IN SOME
PARTS OF THE WORLD.
ALSO THERE ARE MORE THAN
9 MILLION PEOPLE LIVING WITH HIV
THAT DO NOT HAVE ACCESS TO
ANTIRETROVIRAL TREATMENT SO
FINDING WAYS TO ELIMINATE OR
ERADICATE PERSISTENT HIV OR TO
INTRODUCE LONG-TERM CONTROL
WOULD REDUCE CO-MORBID ITS AND
DEATHS AND RELIEVE THE BURDEN
AND STIGMA ASSOCIATED WITH
LIFELONG TREATMENT SO WE BELIEVE
THIS WOULD BE A COMPONENT TO
ENDING THE EPIDEMIC ONCE AR FOR
ALL.
SO THERE'S REASON TO HAVE HOPE
THAT WE CAN ACHIEVE THIS GOAL.
THERE ARE FIVE REPORTS SO FAR OF
CURE BY -- INDIVIDUALS CURED BY
ALLOGENEIC STEM CELL TRANSPLANT
FOR CANCER TREATMENT AND
MULTIPLE INDIVIDUALS WITH
EVIDENCE OF NATURAL CONTROL OR
POST-TREATMENT CONTROL IN THE
ABSENCE OF A SPECIFIC CURE
INTERVENTION.
COMOWN SEVERAL GROUPS HAVE
DEMONSTRATED STRATEGIES THAT
DELAY VIRAL REBOUND FOLLOWING
TREATMENT INTERRUPTION IN ANIMAL
MODELS, BUT THERE'S BEEN LIMITED
SUCCESS WITH CLINICAL
INTERVENTIONS THAT EITHER
CONTROL REBOUND OR SIGNIFICANTLY
REDUCE THE REPLICATION COMPETENT
RESERVOIR.
SO THE SEARCH FOR AN EFFECTIVE
CURE HAS BEEN INCREDIBLY
COMPLEX, AN IN 2011, THE MARTIN
DELANEY COLLABORATORY PROGRAM
WAS DEVELOPED FOR EXACTLY THIS
PURPOSE, BRINGING TOGETHER
ACADEMIC RESEARCHERS, PRIVATE
SECTOR PARTNERS, COMMUNITY
PARTNERS AND GOVERNMENT.
THE PROGRAM IS NAMED FOR MARTIN
DELANEY, FOUNDER OF PROJECT
INFORM AND OUTSPOKEN ADVOCATE
FOR HIV RESEARCH.
COLLABORATORIES HAVE GENERATED
NEARLY 1300 RESEARCH
PUBLICATIONS SINCE THE PROGRAM
BEGAN.
AND IT'S GROWN FROM THE ORIGINAL
THREE COLLABORATORIES TO SIX IN
2016 AND THEN WITH A THIRD
ITERATION IN 2021, THERE WERE 10
COLLABORATORIES FUNDED INCLUDING
A NEW PEDIATRIC AWARD SHOWN ON
THIS MAP.
SO I WOULD NOTE THAT THE MAP IS
SHOWING THE ADMINISTRATIVE HUB
FOR THE AWARDS BUT COLLECTIVELY,
THEY REPRESENT MORE THAN 300
INDEPENDENT LABORATORIES FROM
AROUND THE WORLD.
THE CURRENT STRUCTURE INVOLVES
FLEXIBLE DYNAMIC MILESTONE
DRIVEN RESEARCH PLANS, I'LL TRY
TO WALK YOU THROUGH THE FIRST
RESEARCH FOCUS OR RF1 IS FOCUSED
ON BASIC RESEARCH TO EXPAND
KNOWLEDGE ABOUT PERSISTENT
RESERVOIRS, REBOUND OR POST
TREATMENT CONTROL.
RF2 IS TRANSLATIONAL RESEARCH
FOCUSED ON DURABLE HIV CONTROL
STRATEGIES, AND THE THIRD IS
TRANSLATIONAL STRATEGIES TO
REDUCE THE RESERVOIR SIZE,
EITHER BY ELIMINATION OR
PERMANENT INACTIVATION.
COLLABORATORY LEADERSHIP, THE
LEADERS AND EXECUTIVE COMMITTEE
DEVELOPED MILESTONES AND MAKE
CRITICAL DECISIONS AS THE
SCIENCE EVOLVES AND A SCIENTIFIC
ADVISORY BOARD FOR EACH
COLLABORATORY PROVIDES ANNUAL
FEEDBACK ON PROGRESS AND
PRIORITIES.
AND BECAUSE THIS IS A
COOPERATIVE AGREEMENT, THERE ARE
SEVERAL NIH PROGRAM OFFICERS AND
OTHER STAFF INVOLVED IN THE
SCIENTIFIC AND OTHER ASPECTS OF
THIS PROGRAM.
THERE ARE LEADERS AND
INVESTIGATORS INVOLVED IN EACH
OF THE THREE RESEARCH FOCI, AND
WE REQUIRE INVOLVEMENT OF AT
LEAST ONE PRIVATE SECTOR PARTNER
TO BE MATERIALLY AND
INTELLECTUALLY INVOLVED IN EACH
COLLABORATORY, AND WE ALSO
REQUIRE A COMMUNITY ENGAGEMENT
PLAN THAT INCLUDES COMMUNITY
PARTNERS SUCH AS ADVOCATES AND
COMMUNITY-BASED ORGANIZATIONS TO
INCREASE CURE LITERACY, RESEARCH
LITERACY, AS WELL AS A COMMUNITY
ADVISORY BOARD TO PROVIDE
FEEDBACK TO COLLABORATORY
LEADERSHIP ADDRESSING, FOR
EXAMPLE, SEPTEMBERABILITY AND A.
EACH COLLABORATORY IS ENCOURAGED
TO LEVERAGE OUTSIDE
COLLABORATIONS AND RESOURCES,
INCLUDING INDEPENDENT AND
NETWORK CLINICAL TRIALS, AND
OTHER FUNDED RESEARCH OR
PROGRAMS FOR ACCESS TO
BIOSPECIMENS, ANIMALS, AND
TECHNOLOGY.
THE PROGRAM HAS BROUGHT VALUE TO
THE FIELD BY ENCOURAGING
PARTNERSHIPS, LEVERAGING SHARED
AND COMPLEMENTARY RESOURCES AND
PIVOTING QUICKLY AS TECHNOLOGY
EVOLVES.
IT INCREASES RI CORE WITH
COORDINATED EFFORTS TO DISSOLVE
CYST KREP SEES IN THE FIELD.
EVERY COLLABORATORY IS UNIQUE
WITH THEIR OWN IDEAS, EXPERTISE
AND PARTNERSHIPS.
THERE'S REALLY NO WAY TO COVER
ALL OF THE COLLABORATORIES IN
ONE SHORT PRESENTATION HERE, SO
JUST TO GIVE YOU AN EXAMPLE OF
THE BREADTH OF RESEARCH BEING
CARRIED OUT ACROSS THE PROGRAM,
I'VE SHOWN HERE SEVERAL EXAMPLES
OF HIGH-THROUGHPUT TECHNOLOGIES
TO UNDERSTAND HIV RESERVOIR
DYNAMICS IN BLOOD CELLS AND
TISSUES, EPIGENETICS, CELL
BIOLOGY -- AND IMPROVING IMMUNE
CLEARANCE.
AND LIPID NANOPARTICLE DELIVERY,
GENOME EDITING AND CELL
ENGINEERING APPROACHES.
MANY COLLABORATORY INVESTIGATORS
LINLEVERAGE A WIDE RANGE OF
BIOSPECIMENS THROUGH THEIR
INVOLVEMENT WITH CLINICAL
COHORTS AND TRIALS SUCH AS ACTG,
GATES FOUNDATION, AMFAR, AND
INTERNATIONAL AND
INDUSTRY-SPONSORED TRIALS AND
THERE IS SUBSTANTIAL EFFORT
ACROSS THE COLLABORATORIES TO
COORDINATE ANIMAL AND HUMAN
STUDIES.
SOME HIGH LEVEL EXAMPLES OF
RECENT FINDINGS THAT DEMONSTRATE
THE ACCOMPLISHMENTS ACROSS ALL
OF THE COLLABORATORIES ARE SHOWN
HERE.
FIRST MULTIPLE COLLABORATORIES
HAVE IDENTIFIED DIFFERENT
COMBINATION INTERVENTIONS THAT
CONTROL VIRAL REBOUND AFTER ART
INTERRUPTION IN DIFFERENT ANIMAL
MODELS.
TANIA WILL BE TALKING ABOUT ONE
EXAMPLE OF THIS IN THE NEXT
PRESENTATION.
THEY'VE DEVELOPED NOVEL LATENCY
REVERSAL APPROACHES INCLUDING
DRUGS AND CRISPR SCREENING AND
OTHER APPROACHES TO IDENTIFY
MODULATORS AND MECHANISMS THAT
REGULATE EXPRESSION OF LATENT
HIV AND MAKE -- WITH
REACTIVATION, MAKE RESERVOIR
CELLS MORE SUSCEPTIBLE TO
KILLING.
SEVERAL GROUPS HAVE COORDINATED
STUDIES TO COMPARE THE
PERFORMANCE AND SENSITIVITY AND
SPECIFICITY OF VARIOUS ASSAYS TO
QUANTIFY THE INTACT HIV
RESERVOIR, AND THEY'VE SHOWN
THAT VARIATIONS OF THE IPDA
ASSAY, FOR EXAMPLE, CAN BE USED
TO MEASURE SIV RESERVOIRS.
CURRENTLY SEVERAL LABS ARE
WORKING TO VALIDATE ASSAYS FOR
MEASURING DIFFERENT HIV
SUBTYPES.
AND FINALLY, AS SEVERAL OF THE
COLLABORATORIES ARE USING SINGLE
CELL MOTEOMICS APPROACHES IN
HUMANS AND ANIMAL MODELS TO
BETTER UNDERSTAND MECHANISMS
THAT DRIVES RESERVOIR EXPANSION
AND DECAY.
SO WE JUST REALLY WANT TO
EMPHASIZE, THESE ARE THINGS THAT
REALLY COULD NOT BE DONE WITHOUT
THE EXTENSIVE MULTIDISCIPLINARY
EXPERTISE WITHIN ALL OF THE
COLLABORATORIES.
AND AT THIS POINT, IT'S BECOME
CLEAR THAT COMBINATION
STRATEGIES WILL BE NEEDED FOR AN
EFFECTIVE CURE, SO IT WOULD BE
IMPORTANT TO CONTINUE THESE
EFFORTS.
SO OUR GOALS FOR REISSUE ARE TO
MAINTAIN THE CURRENT OVERALL
SCIENTIFIC AND MANAGEMENT
STRUCTURE WITHIN THE
COLLABORATORIES.
WE ANTICIPATE EACH WILL STILL
HAVE THREE RESEARCH FOCI WITH
BASIC AND TRANSLATIONAL GOALS,
AND IN THE FUTURE, WE'D LIKE TO
EMPHASIZE SYNERGY ACROSS THE
FOCUS AREAS AND DEVELOPMENT OF
STRATEGIES WITH THE GREATEST
PROMISE FOR FUTURE CLINICAL
DEVELOPMENT.
WE EXPECT TO HAVE GREATER
FLEXIBILITY IN THE SCIENTIFIC
OBJECTIVES OF THE RESEARCH FOCI,
SO EACH COLLABORATORY WILL HAVE
THE FREEDOM TO DECIDE WHETHER TO
FOCUS ON BOTH CONTROL AND
ERADICATION OR IF THEY'D LIKE TO
SPECIALIZE IN ONE OR THE OTHER,
DEPENDING ON THE TEAM'S UNIQUE
STRENGTHS AND CAPABILITIES.
BASED ON FEEDBACK FROM MULTIPLE
BOARDS, THE FUTURE PROGRAM WOULD
SUPPORT A ROBUST MODEL FOR
STRONG ACADEMIC COMMUNITY
PARTNERSHIPS, EMPHASIZING
COMMUNITY EDUCATION AND RESEARCH
LITERACY, AND RECOGNIZING THE
IMPORTANCE OF SOCIOBEHAVIORAL
RESEARCH ON THE ACCEPTABILITY
AND FEASIBILITY OF POTENTIAL
CURE STRATEGIES.
TO EXPAND HIV CURE RESEARCH TO A
MORE DIVERSE RANGE OF
PARTICIPANTS AND HIV SUBTYPES,
INTERNATIONAL PARTNERSHIPS WILL
BE STRONGLY ENCOURAGED, AND WE
PLAN TO ALLOW FOREIGN
APPLICATIONS FOR THE FIRST TIME.
WE WANT TO EXPAND INVOLVEMENT OF
EARLY CAREER INVESTIGATORS
ACROSS THE PROGRAM.
SEVERAL COLLABORATORIES ALREADY
DO A GREAT JOB OF THIS, BUT WE
WANT TO MAKE A MORE FORMAL
COMMITMENT TO SUPPORTING THE
NEXT GENERATION OF HIV CURE
RESEARCHERS.
AND FINALLY, WE WANT TO
FACILITATE COLLABORATION ACROSS
THE COLLABORATORY GROUPS THROUGH
A COORDINATION CENTER.
SO I'LL BE TALKING MORE ABOUT
THESE LAST TWO POINTS WHEN WE
GET TO CONCEPT C.
SO WE'RE VERY GRATEFUL FOR THE
REVIEW OF THIS CONCEPT BY RICH
D'AQUILA AND LE AND LOUIS SHACK.
THEY FELT THAT IT NOT ONLY
CONTRIBUTES TO THE HIV CURE
FIELD BUT ALSO IMPACTS AND IS
IMPACTED BY THE BROADER HIV
FIELD.
THEY ALSO NOTED THAT SINCE WE
HAVEN'T YET REACHED THE GOAL OF
FINDING A CURE AND WOULD BE
FURTHER BEHIND WITHOUT THIS
UNIQUE PROGRAM, CONTINUATION OF
THE COLLABORATORIES WAS
COMPELLING.
AS I INDICATED IN THE
PRESENTATION, WE PLAN TO
INCREASE FLEXIBILITY IN THE
RESEARCH FOCI.
THE SCIENTIFIC AREAS FOR
SPECIALIZATION AS A POSSIBILITY,
AND THE REVIEWERS FELT THAT
THFTION IMPORTANT.
THIS
WAS IMPORTANT.
AND THEY INDICATED THAT THEY
FELT THAT TRANSLATIONAL
POTENTIAL AND FEASIBILITY OF THE
PROPOSED INTERVENTIONS FOR
CLINICAL DEVELOPMENT IS
IMPORTANT AND SHOULD BE
CONSIDERED IN THE REVIEW
PROCESS.
SO WE PLAN TO INCORPORATE THIS
IN THE INITIATIVE.
THE REVIEWERS NOTED THAT
COMMUNITY EFFORTS SHOULD REALLY
EMPHASIZE EDUCATION AND
AWARENESS OF CURE RESEARCH, AND
WE AGREE AND I'VE INCORPORATED
THAT INTO THE PRESENTATION, AND
THEY SUGGESTED THAT FUTURE
COLLABORATORIES SHOULD FOCUS ON
THE COMBINATION APPROACHES AND
NOT DEPEND ON ANY PARTICULAR
CLASS OF INTERVENTION.
SO WE PLAN TO HIGHLIGHT THE NEED
FOR CONTINUED INNOVATION AND
DEVELOPING COMBINATION
STRATEGIES.
AND FINALLY, WE HAD SOME
DISCUSSION ABOUT HOW FURTHER
EXPANSION OF THE PROGRAM MAY NOT
BE HELPFUL, BUT THERE WAS
CONCERN THAT KEEPING THE NUMBER
OF COLLABORATORIES THE SAME
WOULD DISADVANTAGE NEW GROUPS.
SO I TRIED TO CLARIFY IN THE
PRESENTATION THAT WE DO NOT PLAN
TO ALLOW RENEWAL APPLICATIONS,
SIMILAR TO HOW WE'VE DONE IT IN
THE PAST.
WE FEEL THAT THIS ENCOURAGES NEW
AND EXISTING GROUPS TO BE ON A
LEVEL PLAYING FIELD.
AND THAT IS THE END, AND I'M
HAPPY TO TAKE ANY QUESTIONS.
>> ARE THERE ANY QUESTIONS?
>> THANKS, THAT'S REAL EXCITING.
SO JUST TO --
>> IF YOU INTRODUCE YOURSELF?
>> KEITH JEROME FROM SEATTLE.
TO PARAPHRASE THE KIND OF THREE
RESEARCH FOCI THAT YOU
DESCRIBED, THERE'S A BASIC
SCIENCE COMPONENT, TRANSLATIONAL
FOR CONTROL OF THE RESERVOIR,
CONTROL OF REBOUND, THIRD ONE
BEING CONTROL OF REBOUND --
>> THE CURRENT ONES, YES.
>> -- CURRENTLY, AND SO IT
WASN'T CLEAR TO ME, ARE THOSE
GOING TO BE CALLED OUT AGAIN IN
THE NEW RFA AS SUCH, OR ARE
THOSE JUST THREE AREAS OF
POTENTIAL RESEARCH BECAUSE
YOU'RE WANTING TO GIVE GROUPS
FLEXIBILITY AND THE ABILITY TO
SPECIALIZE WHICH I REALLY LIKE,
HOW WILL YOU DIRECT -- REVIEW
BASICALLY TO PUT A SPECIALIZED
COLLABORATORY ON SORT OF AN EVEN
PLAYING FIELD WITH A MORE
BROADLY DIRECTED ONE?
>> SO FIRST OF ALL, I THINK
WE -- THERE'S DETAILS THAT WILL
BE MORE CLEAR WHEN THE
INITIATIVE COMES OUT BUT AT THIS
POINT WE FEEL THE IMPORTANCE OF
BOTH BASIC SCIENCE AND
TRANSLATIONAL RESEARCH, AND JUST
IF I UNDERSTAND YOUR LAST
QUESTION, SO IF THERE'S AN
EXISTING PROGRAM WHO WOULD BE
APPLYING IN THE FUTURE, THEY
WOULD NEED TO ADHERE TO THE NEW
STRUCTURE.
SO WHATEVER THAT STRUCTURE MAY
BE.
>> I THINK I WASN'T SUPER CLEAR.
>> OH, SORRY.
>> SO EVERYBODY IS NEW, SO NEW
COLLABORATORY A MIGHT BE VERY
MUCH FOCUSED ON CONTROL OF
REBOUND, JUST AS AN EXAMPLE.
ANOTHER ONE MIGHT BE MORE
BROAD-BASED.
WE HAVE SORT OF THE THREE THINGS
THAT YOU MENTIONED.
SO I JUST AM CURIOUS AS TO HOW
YOU WILL PRESENT THIS OR
ENCOURAGE YOU TO BE THOUGHTFUL
ABOUT HOW YOU PRESENT THIS TO
REVIEW PANELS SO THAT A FOCUSED
COLLABORATORY MIGHT BE COMPETING
ON A LEVEL PLAYING FIELD WITH
ONE THAT IS MORE BROADLY
DIRECTED.
DOES THAT MAKE SENSE, THAT FOCUS
VERSUS BREADTH IN HOW YOU ENSURE
AN EVEN REVIEW PROCESS.
>> RIGHT.
WELL, I THINK ALL OF THEM WOULD
NEED TO SHOW THE CAPACITY FOR
FUTURE CLINICAL DEVELOPMENT, ALL
OF THEM WOULD NEED TO SHOW
SYNERGY AMONG THEIR BASIC AND
TRANSLATIONAL EFFORTS.
I THINK ALL OF THEM WILL NEED TO
SHOW, AS THEY'VE DONE IN THE
PAST, ADAPTABILITY TO CHANGING
SCIENCE, SO I THINK OVERALL THE
GOAL IS TO FIND AN AVENUE
TOWARDS A CURE.
SO I THINK HOW THEY DO THAT WILL
LIKELY NEED TO REMAIN SIMILAR IN
TERMS OF FOCI TO ENHANCE BASIC
SCIENCE AND BETTER UNDERSTANDING
ABOUT THE RESERVOIRS, AND
TRANSLATIONAL APPROACHES THAT
WILL ADDRESS EITHER CURE --
SORRY -- EITHER CONTROL OR
ERADICATION OR BOTH.
AND HOWEVER THEY CHOOSE TO
PRESENT THAT, I THINK THE
REVIEWERS ULTIMATELY WILL BE
LOOKING AT THE OVERALL
INSTRUCTIONS FOR THE PROGRAM.
SO CARL, DID YOU WANT TO HAVE
ANOTHER COMMENT THERE?
>> I'D JUST POINT OUT THAT WE
HAVE A CALL WITH REVIEWERS
BEFOREHAND, SO WE'LL MAKE IT
CLEAR TO THEM THAT ALL
APPLICATIONS SHOULD BE REVIEWED
ON THEIR OWN MERIT, WHETHER
THEY'RE SPECIALIZED IN ONE AREA
OR IF THEY'RE BROAD-BASED.
>> HI, SEEMA SHAH.
SO I JUST WANTED TO BUILD ON
THAT BECAUSE I THINK IT WOULD BE
REALLY IMPORTANT IN THAT CALL TO
BE CLEAR TO REVIEWERS THE
POTENTIAL REVIEW OF BROAD
APPLICATIONS, I THINK WHAT YOU
WERE SUGGESTING.
BUT I THINK A LOT OF TIMES
REVIEW COMMITTEES TEND TO -- YOU
KNOW, SAYING SOMETHING IS VAGUE
OR UNCLEAR OR THERE ISN'T
SUPPORT FOR A CERTAIN STRATEGY
IS AN EASY CRITIQUE, AND I THINK
FOCUSED -- TEND TO DO BETTER SO
IF THERE'S REALLY THIS EMPHASIS
ON WANTING TO FUND BROAD
ADAPTABLE STRATEGIES, IT MAY BE
IMPORTANT TO EMPHASIZE THAT.
SO I JUST WANTED TO UNDERSCORE
WHAT YOU WERE SAYING AND -- IF
THAT --
>> GENERALLY, I THINK WE WERE
EXPRESSING THE SAME CONCERNS,
ALTHOUGH I THINK MINE WAS SORT
OF ON OPPOSITE SIDE OF THE FENCE
THERE ACTUALLY.
THIS PARTICULAR MECHANISM HAS
FAVORED THE BIGGEST, BROADEST
GROUP OF PEOPLE DOING EVERYTHING
YOU CAN DO.
AND THAT MAY BE A VERY VALID WAY
TO DO THINGS.
IT PROBABLY IS NOT THE ONLY WAY.
SO I THINK THAT AS A PROGRAM, A
DIVERSITY OF APPROACHES, WE
DON'T KNOW HOW TO CURE THIS
VIRUS, SO I THINK DIVERSITY OF
APPROACH IS ACTUALLY IMPORTANT.
>> RIGHT.
I'M HOPING THAT BY THE TIME WE
GET TO CONCEPT C, YOU COULD SEE
HOW THERE WOULD BE A POTENTIAL
FOR COORDINATION OF DIFFERENT
GROUPS THAT MIGHT HAVE
COMPLEMENTARY BUT MORE
SPECIALIZED APPROACHES AS WELL
AS THE MORE BROAD.
>> QUICK SEPARATE QUESTION.
>> YES.
>> FOR THE FOREIGN APPLICATIONS,
WOULD THEY BE STANDALONE FOREIGN
APPLICATIONS OR IS THE IDEA THAT
IT WOULD BE -- COULD IT BE
ENTIRELY FOREIGN OR --
COLLABORATING WITH U.S.-BASED
SITES?
>> I THINK WE WOULD BE OPEN TO
MULTIPLE POSSIBILITIES THERE.
SO AS LONG AS THE SCIENTIFIC
MERIT IS WHAT IT NEED TO BE AND,
YOU KNOW, ALL OF THESE PROGRAMS
ARE VERY COLLABORATIVE AND MANY
ALREADY INCLUDE FOREIGN
COLLABORATIONS.
SO -- BUT WE'VE NEVER ALLOWED A
FOREIGN APPLICATION COMING IN
BEFORE, SO ANYWAY, YEAH.
>> THANK YOU.
>> GREAT.
THANK YOU.
>> ARE THERE ANY QUESTIONS
ONLINE?
YOU GUYS CAN ASK QUESTIONS IF
YOU'D LIKE.
>> YES, I HAVE A QUESTION.
HI, THIS IS CINDY DE DERDEYN,
UNIVERSITY OF WASHINGTON,
SEATTLE.
TO ENCOURAGE PEOPLE PUTTING IN
THESE APPLICATIONS TO FOCUS ON
THE LIMITATIONS OF THE ANIMAL
MODELS AND DO SOME COMPARATIVE
STUDIES, YOU KNOW, A LOT OF
THESE -- I FEEL LIKE IT'S GOTTEN
VERY NARROW IN TERMS OF, YOU
KNOW, USING THE BARCODED SIV AND
THESE SHORT WINDOWS BEFORE ART
IS INITIATED, AND THAT IT'S
COMING OUT THAT THERE REALLY ARE
DIFFERENCES BETWEEN THESE
RESERVOIRS AND SIV IN THE ANIMAL
MODELS AND PEOPLE IN REAL LIFE
WHO ARE ON TREATMENT AND MAY
HAVE BEEN INFECTED FOR YEARS
BEFORE THEY WENT ON TREATMENT.
SO I WONDER IF THIS WAS AN
OPPORTUNITY TO HAVE THAT BE A
FOCUS OR A FEATURE OR A PRIORITY
OF SOME OF THESE COLLABORATORIES
TO BETTER UNDERSTAND WHAT ARE
THE LIMITATIONS OF THE ANIMAL
MODELS, AND HOW DO MAKE THEM
MORE TRANSLATABLE.
>> ABSOLUTELY.
I THINK THAT WOULD BE AN
EXCELLENT -- THANK YOU FOR
BRINGING THAT UP.
THE GOAL IS TO MOVE TOWARDS A
CLINICAL CURE, SO I THINK
DEFINITELY THAT THIS CERTAINLY
WOULD BE A GREAT OPPORTUNITY TO
HAVE DIFFERENT GROUPS LOOKING AT
DIFFERENT MODELS AND WAYS TO
DEMONSTRATE THE PRELIMINARY
STUDIES THAT COULD BE MOST
PROMISING TOWARDS A CLINICAL
STRATEGY.
>> I BELIEVE THERE'S ONE LAST
QUESTION ONLINE.
THEN WE'RE GOING TO HAVE TO MOVE
ON.
>> YES, THIS IS TIM HENRICH FROM
UCSF.
I THINK ONE OF THE REAL
STRENGTHS OF THE DELANEY
COLLABORATORIES IS REALLY THE
FLEXIBILITY TO ADAPT TO DATA
THAT'S GENERATED TO HAVE A GROUP
THAT CAN RAPIDLY RESPOND WITHOUT
HAVING TO BE FOCUSED ON TOO MANY
SPECIFIC PROJECT OUTCOMES AND
PEOPLE HAVE THAT FLEXIBILITY.
BUT I ALSO WONDERED, YOU KNOW, I
GUESS FOR HISTORICAL OBVIOUS
REASONS THAT ELIMINATING
CLINICAL TRIALS WITHIN THE
GEOCOLLABORATORIES NOT JUST FOR
FUNDING ISSUES BUT REGULATORY
AND OTHER ISSUES, BUT WHETHER
THERE'S A WAY TO CHALLENGE A
RELATIVELY STRICT POLICY OF NOT
HAVING CLINICAL TRIALS OUTSIDE
OF SPECIFIC MECHANISMS TO DO
SMALLER PATHOGENESIS, WHETHER
THEY INVOLVE APIs OR OTHER
TYPES OF QUESTIONS THAT ACTUALLY
MAY BE IMPORTANT WHEN LOOKING AT
THESE PATHOBIOLOGICAL MECHANISMS
ON A SMALLER SCALE.
NOT FOR A LARGE CLINICAL TRIAL,
BUT WONDERING IF THAT COULD ALSO
BE A COMPONENT GOING FORWARD ON
SOME OF THESE CLINICAL
COLLABORATORIES.
>> AS FAR AS PILOT STUDIES?
IS THAT WHAT YOU'RE SUGGESTING?
>> YES, KIND OF SMALLER PILOT
STUDIES THAT ARE NOT
AGENCY-DEFINED INTERVENTIONS.
>> YEAH, I MEAN, WE'VE
DEFINITELY BEEN DISCUSSING THAT
QUITE A BIT AS FAR AS HOW TO
SUPPORT SUCH SMALL PILOT STUDIES
AND SOME OF MY COLLEAGUES HERE
MIGHT WISH TO ANSWER THAT
POTENTIALLY BUT WE DEFINITELY
ARE LOOKING AT A POSSIBLE WAY TO
SUPPORT THOSE TYPES OF STUDIES.
>> TIM, THIS IS CARL.
I'D JUST MAKE THE POINT THAT WE
WORKED WITH ACTG TO HAVE
SPECIFIC SOLICITATION TO
ACCOMMODATE SMALL CLINICAL
TRIALS.
WE FOUND IN THE SECOND ITERATION
WHEN WE ALLOWED CLINICAL TRIALS
IT WAS REALLY A BIG DISTRACTION
TO TRY TO SQUEEZE A CLINICAL
TRIAL INTO THE FIVE-YEAR FUNDING
PLAN OF THE COLLABORATORY, SO IT
WAS A BIG DISTRACTION
FINANCIALLY AS WELL AS JUST THE
ATTENTION FROM THE SCIENCE TO
JUST THE LOGISTICS OF CARRYING
OUT CLINICAL TRIALS.
SO THE FEEDBACK WE RECEIVED WHEN
WE DID AN EVALUATION FROM AN
INDEPENDENT GROUP WAS THAT IT'S
PROBABLY BEST TO CONTINUE THAT.
THOSE TRIALS ARE BEST DONE
OUTSIDE THE COLLABORATORY
STRUCTURE UNDER SEPARATE FUND
FUNDING.
>> SO I THINK WE'LL MOVE ON TO
THE NEXT PRESENTATION, AND IF
YOU CAN EITHER VOTE NOW OR WAIT
UNTIL WE'VE DONE ALL THREE.
>> MY NAME IS TANIA LOMBO,
PROGRAM OFFICER AT THE
PREVENTION SCIENCES PROGRAM.
TO PRESENT CONCEPT B INITIATIVE
FOR APPROVAL TITLED MART TIN
DELANEY COLLABORATORIES FOR
PEDIATRIC HIV CURE RESEARCH.
THE PURPOSE OF THIS INITIATIVE
WILL BE TO ACCELERATE RESEARCH
TO ADDRESS MAJOR OBSTACLES TO
THE ERADICATION OF HIV INFECTION
OR LONG-TERM ART-FREE CONTROL OF
VIRAL REBOUND IN PEDIATRIC
INDIVIDUAL LIVING WITH HIV.
THIS INITIATIVE WILL FOSTER A
COLLABORATIVE AND DYNAMIC
PROGRAM STRUCTURE, LEVERAGING
SHARED RESOURCES, FACILITATING
COLLABORATIONS AMONG ACADEMIA,
INDUSTRY, GOVERNMENT, AND
COMMUNITY, WHILE TRAINING THE
NEXT GENERATION OF PEDIATRIC HIV
CURE RESEARCHERS.
THIS IS A REISSUE, AND THE PLAN
IS TO USE THE UM1 GRANT
MECHANISM.
WE HAD ANTICIPATED ONE AWARD,
AND HERE YOU CAN SEE OUR
POTENTIAL CO-FUNDING PARTNERS
WITHIN NIH.
FROM THE 2023 REPORT, WE KNOW
FROM THE GLOBAL POPULATION,
LIVING WITH HIV, AN ALARMING
NUMBER OF 1.5 MILLION CHILDREN
LIVE WITH THIS VIRUS.
AND ONLY 57% RECEIVE
ANTIRETROVIRAL TREATMENT.
THIS REALITY AND PARTICULAR
CONSIDERATIONS PROMPTED US TO
INITIATE A SEPARATE
COLLABORATORY SOLELY DEDICATED
TO PEDIATRIC POPULATIONS.
BEFORE I COME TO THOSE DETAILS,
I WANT TO REVIEW WITH YOU SOME
UNIQUE IMMUNOLOGIC
CONSIDERATIONS FOR PEDIATRIC HIV
CURE RESEARCH.
SO WE KNOW THE IMMUNOLOGIC
ENVIRONMENT OF THE FETUS IN
UTERO IS ANTI-INFLAMMATORY WITH
POTENTIAL IMPLICATIONS FOR
RESERVOIR SIZE AND STABILITY.
THE ANTI-INFLAMMATORY
ENVIRONMENT PROMOTES LOW IMMUNE
ACTIVATION, AND LOW EXPIRATION
EXPRESSIONOF CCR5.
AS IS SHOWN IN THIS PICTURE, AND
THIS SLIDE, THE TIMING OF
EXPOSURE IS KNOWN, SO THE
PERINATAL HIV INFECTION ALLOWS A
RAPID ART INITIATION.
USUALLY BETWEEN THE 48 HOURS OF
LIFE TO 3 MONTHS OF AGE.
AND THIS IS PROVIDING AN
OPPORTUNITY, A WINDOW OF
OPPORTUNITY TO INTERVENE VERY
EARLY IN THE COURSE OF INFECT
INFECTION.
FROM THE VIROLOGIC
CONSIDERATIONS, WE KNOW THERE IS
A DIFFERENT DISTRIBUTION OF CELL
TYPES CONTAINING THE HIV
RESERVOIR COMPARED TO ADULTS.
WE KNOW FROM EARLY TREATMENT
STUDIES THAT THE RESERVOIRS IN
CHILDREN ARE GENERALLY SMALLER,
MORE HOMOGENEOUS, AND THE
RESERVOIR HAS A FASTER DECAY,
AND IN PARTICULAR, THERE IS A
MINIMAL CENTRAL NERVOUS SYSTEM
RESERVOIR.
HERE I'M LISTING A FEW CASES OF
ART 3 REMISSION THAT HAVE BEEN
REPORTED IN PERINATAL INFECTIONS
SUCH AS THE MISSISSIPPI BABY,
FRENCH PERINATAL COHORT CHILD
STUDY AN THE SOUTH AFRICAN CHILD
STUDY.
SHOWING VERY EARLY ART IN
NEONATES WITH IN UTERO HIV SHOW
REDUCED VIRAL RESERVOIRS AND
ENABLED MORE THAN 48 WEEK
ART-FREE REMISSION IN
4 PARTICIPANTS.
PRACTICAL EXAMPLES JUSTIFY THE
NEED OF A HIGHLY COORDINATED
RESEARCH EFFORTS TO FIND AN HIV
CURE FOR CHILDREN LIVING WITH
HIV.
SO OUR INSTITUTE RESPO RESPONDEO
THIS NEED BY AWARDING IN 2021
THE FIRST PEDIATRIC MDC
COLLABORATORY.
IT FUNCTIONS MAINLY UNDER THE
SAME PREMISE AS THE ADULT
COUNTERPART WITH A FEW
DIFFERENCES.
THIS GROUP IS HIGHLY
INTEGRATIVE, COLLABORATIVE AND
SYNERGISTIC, AND WORKING VERY
ACTIVE ON BUILDIN BUILDING STRAC
PARTNERSHIPS WITH OTHER
COLLABORATORIES, OTHER NETWORKS
AND OTHER STAKEHOLDERS TO
DELIVERY SOURCES AND TO BUILD
EFFECTIVE PARTNERSHIPS.
THE PEDIATRIC MDC HAS AN EXTRA
FOCUS AS YOU SEE IN THE FIGURE
HERE, RESEARCH FOCUS 4,
DEDICATED TO ASSAY DEVELOPMENT
OPTIMIZATION AND IMAGING.
AND AS A REMINDER, THE MAIN
OBJECTIVE OF THIS COLLABORATORY
IS TO ACHIEVE AND SUSTAIN
ART-TREE CONTROL OF HIV
REPLICATION IN PEDIATRIC
POPULATIONS.
THE NEXT SLIDE THAT I WANT TO
REVIEW WITH YOU A FEW SCIENTIFIC
ACCOMPLISHMENTS AND INTERESTING
PROGRESS OF THIS COLLABORATORY.
SO JUST TO REMIND EVERYONE, THE
COLLABORATORY IS PART OF THE
LARGER AILDZ AIDS MDC PROGRAM.
FOR THESE FOUR EXAMPLES, I WANT
TO BRING YOUR ATTENTION TO THE
FIRST ONE WHERE THE RESEARCHERS
ARE USING EARLY ART COUPLED WITH
AAV-VECTORED DELIVERY OF ECD4-IG
AND 10-1074.
THEY HAVE FOUND SUBSTANTIAL
DELAYED VIRUS REBOUND IN
PERINATALLY SHIV-INFECTED INFANT
MACAQUES FOLLOWING A ATI.
ANOTHER GROUP IS LOOKING AT
EARLY LIFE INNATE IMMUNE SEX
DIFFERENCES SELECTIVELY
INFLUENCE VERTICAL HIV
TRANSMISSION AND MODULATE
POST-TREATMENT CONTROL IN
CHILDREN.
SOME PRELIMINARY ANALYSES OF
HOST GENETIC AND IMMUNE MARKERS
HAVE IDENTIFIED POTENTIAL HOST
IMMUNOGENETIC FACTORS
CONTRIBUTING TO VIRAL CONTROL,
AND FINALLY, ONE OF OUR GROUPS
IN SOUTH AFRICA IS LEADING UP A
COLLABORATIVE PROJECT TO
UNDERSTAND THE MECHANISMS AND
CELL SOURCES OF HIV PERSISTENCE
IN CSF AND ITS IMPLICATIONS IN
NEUROPATHOGENESIS AND
CONSEQUENCES TO CNS INFECTION.
I WANT TO SHOW MAIN RESULTS IN
AAV-DRIVEN EXPRESSION OF ECD4-IG
AND 10-1074, 7 OUT OF 10
AAV-TREATED INFANT MACAQUES
REMAINED AVIREMIC FOR MORE THAN
30 WEEKS AFTER ATI.
THE PERSISTENCE OF MONOCLONAL
ANTIBANTIBODIES IN THE RED DOTSS
SUPPRESSED IN THE CONTEXT OF THE
ANTIBODY EXPRESSION.
SO THE BOTTOM LINE OF THESE
RESULTS ARE SHOWING THAT THERE
IS A CLEAR CORRELATION BETWEEN
THE EXPRESSION OF THE ANTIBODIES
AND THE VIRUS SUPPRESSION.
THIS IS A VERY PROMISING STORY
COMING FROM THE PEDIATRIC MDC,
AND CURRENTLY OUR RESEARCH IS
EVALUATING PATHS TO MOVE TO
CLINICAL EVALUATION.
LAST BUT NOT LEAST, THE FIRST
COLLABORATORY IS HIGHLY FOCUSED
ON BRINGING -- THEY ARE WORKING
ON DIFFERENT FRONTS.
FIRST THEY ARE OPTIMIZING
STRATEGIES TO REACH NEW
STAKEHOLDERS, AND DEVELOPMENT OF
RESEARCH LITERACY MATERIALS,
SUPPORT KNOWLEDGE DISSEMINATION
INVOLVING VOICES OF PEDIATRIC
HIV CURE, IN THIS WAY, TO ENABLE
COMMUNITY PARTICIPATION AND
DISCUSSIONS TO SHAPE THE
PEDIATRIC CURE AGENDA.
SO MOVING FORWARD, WHEN WE ARE
LOOKING ON THE REISSUE OF THIS
PEDIATRIC MDC AS PART OF THE
GLOBAL PROGRAM, WE WANT TO BUILD
ON THE CURRENT FRAMEWORK
ALLOWING GREATER FLEXIBILITY
WITHIN THE RESEARCH FOCI, IN
PARTICULAR FOR THE PEDIATRIC, WE
ARE LOOKING TO STIMULATE CERTAIN
AREAS AS DESCRIBED IN THESE
BULLET POINTS.
FIRST, CHARACTERIZATION OF THE
RESERVOIR LATENCY AND DYNAMICS
ACROSS DEVELOPMENTAL STAGES
INCLUDING DIFFICULT TO ACCESS
TISSUES SUCH AS CNS.
SECOND, THE FUTURE PEDIATRIC MDC
WILL EXPAND ON TAILORED
STRATEGIES FOR PEDIATRIC HIV
RESERVOIR, AND KEEP THE
DEVELOPMENT OF SPECIALIZED AND
NEW TOOLS IN VITRO AND OTHER
MODELS, ASSAYS, IMAGING, AND
ANIMAL MODELS TAILORED TO
PEDIATRIC RESEARCH.
THE FUTURE SHOULD KEEP AN EYE ON
INCLUSION OF DIVERSIFIED
PEDIATRIC POPULATIONS INCLUDING
THOSE WITH CO-INFECTIONS OR WITH
CHRONIC SUBSTANCE USE OR
EXPOSURE.
FINALLY, AN ASPECT THAT WE
WILL -- IS TO PRIORITIZE AND
STRATEGIZE THE INCLUSION OF
PRODUCT DEVELOPMENT FRAMEWORK
FOR PRE-CLINICAL TO CLINICAL
TRANSLATION OF PROMISING HIV
REMISSION STRATEGIES.
AND WE THINK THAT THIS ACTIVITY
WILL REQUIRE NOT ONLY INTRINSIC
INFRASTRUCTURE AND
COLLABORATIONS, BUT ALSO
COLLABORATION WITH EXTERNAL
PARTNERS.
IN THE AREA OF COMMUNITY
ENGAGEMENT PROGRAM, KEEP
EXPANDING THE HEALTH LITERACY,
KNOWLEDGE DISSEMINATION, WITH
THE ULTIMATE GOAL TO SHARE THE
PEDIATRIC HIV CURE AGENDA.
WE ARE LOOKING TO INCLUDE AND
EXPAND SOASH R. SOCIOBEHAVIORAL
ASPECTS IN PARTICULAR TO
PEDIATRIC HIV CURE RESEARCH, BY
INCLUDING END USER ACCEPTABILITY
OF PROMISING HIV CURE
STRATEGIES, AND LOOKING AT THE
INTERSECTION OF MENTAL HEALTH
AND HIV PERSISTENCE.
AND FINALLY AS PART OF THE
GLOBAL MDC PROGRAM, THE
PEDIATRIC EMPHASIS WILL TRAIN
THE NEXT GENERATION OF PEDIATRIC
HIV CURE RESEARCHERS AND SHOULD
BE AN ACTIVE PARTICIPANT OF
FUTURE CROSS-MDC COLLABORATIONS
AND COORDINATIONS THROUGH THE
NEW COORDINATION CENTER.
AND DIANE IS GOING TO EXPLAIN
THAT A LITTLE MORE IN THE NEXT
PRESENTATION.
SO WE HAD THE PLEASURE TO MEET
DR. ELAINE ABRAMS AND GRACE
ALDROVANDI.
THEY REVIEWED THIS PROPOSAL AND
AGREED THAT IT SHOULD BE
APPROVED, AND THEY AGREE THAT
THE PEDIATRIC MDC WILL BE
PROVIDING A HOME FOR AND
FOSTERING INTERDISCIPLINARY
COLLABORATION THAT SHOULD
ACCELERATE SCIENTIFIC INQUIRY
AND ACHIEVEMENTS.
THEY WANTED US TO CLARIFY THE
MEANING OF "TRANSLATIONAL
READINESS" WITHIN THE PEDIATRIC
MDC.
WE WORKED THIS OUT IN THE -- AND
WE DESCRIBED WHAT WILL BE THE
EXPECTATIONS OF THIS POTENTIAL
FRAMEWORK FOR DEVELOPMENT, AND
PROGRAM WILL BE SURE TO WORK ON
THE FUTURE INITIATIVE TO INCLUDE
EXPECTATIONS AND REVIEW CRITERIA
TO ENSURE THAT THERE'S A
FRAMEWORK FOR POSITIVELY
ADVANCING PROMISING HIV
PREVENTION STRATEGIES TO
CLINICAL TESTING FOR CHILDREN.
WITH THIS, I FINISH, AND I'M
HAPPY TO TAKE ANY QUESTIONS OR
FEEDBACK IF THERE IS TIME.
THANK YOU.
>> I'M GOING TO START ONLINE.
ANY QUESTIONS?
AND HOW ABOUT ANYBODY HERE?
OKAY.
THANK YOU VERY MUCH.
FOLKS CAN VOTE NOW OR AFTER THE
NEXT PRESENTATION.
THANKS AGAIN.
HELLO.
THE FINAL CONCEPT THAT WE'LL BE
PRESENTING TODAY IS THE MARTIN
DELANEY CLAB TRIS COORDINATION
CENTER, AND THE PUMPS PURPOSE A
SIL TATE COMMUNICATION,
COLLABORATION AND COORDINATION
AMONG THE INDIVIDUAL MARTIN
DELANEY COLLABORATORIES AND KEY
STAKE OLDERS.
THIS WOULD BE A NEW INITIATIVE
USING THE U01, AND $.5 MILLION,
THIS WOULD INCREASE IN YEARS
2 THROUGH A 5 TO SUPPORT A
SPECIAL PROGRAM THAT I'LL TALK
ABOUT FOR NEXT GENERATION
RESEARCHERS.
SO WE ANTICIPATE FUNDING ONE
AWARD.
SO THE EARLIER PRESENTATIONS --
THIS SHOWS THE ORGANIZATION OF
THE ENTIRE PROGRAM.
SO IF YOU START AT THE BOTTOM OF
THE SLIDE, YOU'LL SEE WE HAVE
OUR TRANS-NIH PROGRAM MANAGEMENT
TEAM, WHICH INCLUDES NIAID, AND
OUR PARTNER INSTITUTES.
FROM NIH.
AND BASICALLY MONITOR THE
OVERALL PROGRESS OF EACH
COLLABORATORY.
THEN WITHIN DAIDS, THERE ARE
SEVEN PROGRAM OFFICERS,
INCLUDING MYSELF AND TANIA, WHO
ARE FROM THREE DIFFERENT
BRANCHES THAT OVERSEE THE
DIFFERENT COLLABORATORY AWARDS.
THUS WE HAVE ADDITIONAL PROGRAM
OFFICERS AND PROJECT SCIENTISTS
THAT ARE INVOLVED INFORMALLY IN
THE PROGRAMS.
EACH COLLABORATORY HAS THEIR OWN
UNIQUE INTERACTIONS WITH PRIVATE
SECTOR PARTNERS, COMMUNITY
PARTNERS, CLINICAL RESEARCHES,
NETWORKS SUCH AS ACTG AND IMPACT
AS AN EXAMPLE, INTERNATIONAL
PARTNERS, AND OTHER FUNDERS
INCLUDING GATES FOUNDATION AND
AMFAR.
SO THE RATIONALE FOR
COORDINATION IS THAT WE FEEL
FACILITATING COMMUNICATION
ACROSS THE PROGRAM WILL HELP
MANAGE THE COMPLEXITY, AND
PROVIDING OPPORTUNITIES FOR
SYNERGY WILL ADD VALUE FOR
OVERCOMING THE COMMON SCIENTIFIC
CHALLENGES THAT ALL THE
COLLABORATORIES ARE FACING.
COMMUNICATION AND COLLABORATION
AND COORDINATION ACROSS THE
PROGRAM WILL STRENGTHEN THE
COLLABORATORY'S COLLECTIVE
EFFORTS AND HAVING A CENTRALIZED
INFRASTRUCTURE TO UNIFY THE
PROGRAM AND ALLOW THE MDCs TO
MORE EFFICIENTLY WORK TOGETHER
TO OPTIMIZE CURE STRATEGIES.
SO THE VISION FOR THE PROGRAM IS
TO SUPPORT INTEGRATION OF THE
SCIENCE AND OPERATIONS OF THE
COLLABORATORIES, WHILE STILL
ALLOWING THE INDIVIDUAL GROUPS
TO FOCUS ON THEIR UNIQUE
SCIENCE.
SO THE COORDINATION CENTER
ESSENTIALLY WILL HELP THE GEARS
TURNING SMOOTHLY SIMILAR TO
OTHER SUCCESSFUL NIAID-SUPPORTED
COORDINATION CENTERS, INCLUDING
HANK FOR THE HIV CLINICAL TRIALS
NETWORK, AND THE CREEDS
COORDINATION CENTER FOR EMERGING
INFECTIOUS DISEASES.
SO KEY ROLES WILL INCLUDE
FACILITATING THE EXCHANGE OF
IDEAS AND BEST PRACTICES,
COORDINATING CRITICAL ACTIVITIES
AND ENGAGING EXTERNAL
STAKEHOLDERS FOR NEEDED
CONSULTATIONS.
SIMILAR TO THE FUNCTION OF, FOR
EXAMPLE, THE UC BERKELEY FORUM
FOR COLLABORATIVE RESEARCH.
WHILE COLLABORATORIES GENERALLY
HAVE BEEN SUPPORTIVE OF EARLY
STAGE INVESTIGATORS, WE'VE NEVER
HAD A FORMAL MECHANISM FOR THIS
IN THE PROGRAM.
SO IN YEARS 2 THROUGH 5, THE
COORDINATION CENTER WILL SUPPORT
A PROGRAM TO CONNECT, SUPPORT
AND MENTOR A SELECT GROUP OF
EARLY STAGE INVESTIGATORS FROM
OUTSIDE THE COLLABORATORY
NETWORK. ANOTHER IMPORTANT
FUNCTION WILL BE TO
COORDINATE -- SHOWN IN THE
CENTER HERE, TO COORDINATE A
GROUP OF COMMUNITY AND
SCIENTIFIC CONSULTANTS WHO WILL
PROVIDE FEEDBACK ON THE PROGRAM
AS A WHOLE TO THE
COLLABORATORIES AND TO NIH.
SO THE OBJECTIVE OF THE PROGRAM
IS TO ESTABLISH A COMPREHENSIVE
CENTRALIZED -- ESTABLISH A
COMPREHENSIVE COORDINATION
CENTER THAT SERVES AS A PLATFORM
FOR A MORE INTEGRATED AND
STRATEGIC COLLABORATORY RESEARCH
PROGRAM.
THE COORDINATION CENTER WOULD
PROVIDE CENTRALIZED SUPPORT FOR
ACTIVITIES AND COLLABORATION
ACROSS THE PROGRAM.
SERVE AS A NEUTRAL HUB FOR
EFFECTIVE COMMUNICATION AT
MULTIPLE LEVELS.
AND WOULD DEVELOP A
PUBLIC-FACING WEBSITE THAT WOULD
PROVIDE CENTRALIZED INFORMATION
ABOUT THE PROGRAM AND HELP
ENGAGE EXTERNAL STAKEHOLDERS AND
NEXT GENERATION RESEARCHERS.
SO JUST TO SHOW SOME EXAMPLES OF
OPPORTUNITIES FOR WHAT THE
COORDINATION CENTER COULD DO,
CURRENTLY THE COLLABORATORIES
ARE REQUIRED TO ATTEND ONE JOINT
SCIENTIFIC MEETING A YEAR, AND
BASED ON FEEDBACK FROM MULTIPLE
INVESTIGATORS AND SAB MEMBERS,
IT SEEMS IT WOULD BE MORE
HELPFUL TO HAVE MORE FREQUENT
OPPORTUNITIES FOR INTERACTIONS.
SO THE COORDINATION CENTER COULD
ORGANIZE THESE
CROSS-COLLABORATORY SCIENTIFIC
MEETINGS AND ALSO ESTABLISH
TOPICS OF SPECIFIC WORKING
GROUPS AS THE NEED ARISES.
FOR EXAMPLE, THE QUESTION THAT
CAME UP EARLIER ON DIFFERENT
ANIMAL MODELS AND THERE IS NO
PERFECT ANIMAL MODEL, BUT
DIFFERENT ANIMAL MODELS CAN BE
USEFUL FOR DIFFERENT THINGS AND
HOW CAN WE COORDINATE THE USE OF
ANIMAL MODELS TO MOST E
EFFICIENTLY HEAD TOWARDS A
CLINICAL SOLUTION.
ALSO THE COORDINATION CENTER
COULD FACILITATE CONSULTATIONS
WITH CLINICAL TRIAL NETWORKS,
INTERNATIONAL ORGANIZATIONS,
REGULATORY AGENCIES, INDUSTRY
AND COMMUNITY, JUST TO GET
ADDITIONAL PERSPECTIVES THAT
COULD BENEFIT THE ENTIRE PROG
PROGRAM.
THE COORDINATION CENTER ALSO
COULD PROMOTE EFFECTIVE
COMMUNICACOMMUNICATION AND ADMIE
SUPPORT BY COORDINATING
INFORMATION AND RESEARCH
EXCHANGE ACROSS THE
COLLABORATORIES, ESTABLISHING
HARMONIZED POLICIES AND MAN
AMOMANAGEMENT PRACTICES, TRACKIG
AND DISSEMINATING OVERALL
PROGRESS AND OUTPUTS AND
ORGANIZING EXTERNAL SCIENTIFIC
AND COMMUNITY FEEDBACK FOR THE
ENTIRE PROGRAM.
THE COORDINATION CENTER WOULD BE
EXPECTED TO SUPPORT INDIVIDUAL
COLLABORATORY EFFORTS TO FOSTER
AND EVALUATE THEIR COMMUNITY
PARTNERSHIPS AND ACTIVITIES, AND
TO FACILITATE COMMUNICATION
ACROSS THE TEAMS TO BROADEN AND
STRENGTHEN THESE EFFORTS.
THE COORDINATION CENTER WOULD
HELP THE COLLABORATORIES PROMOTE
CONSISTENT USE OF PLAIN LANGUAGE
RESEARCH SUMMARIES AND ADHERENCE
TO THE NIAID HIV LANGUAGE GUIDE,
WHICH AS WE'VE HEARD HAS BEEN
RECENTLY UPDATED.
AND IT COULD ALSO HELP THE
COLLABORATORIES IDENTIFY
STRATEGIES TO SUPPORT
SOCIOBEHAVIORAL RESEARCH FOCUSED
ON ACCEPTABILITY OF POTENTIAL
CURE INTERVENTIONS.
AS I MENTIONED, THE COORDINATION
CENTER WOULD DEVELOP A FORMAL
PROGRAM TO ENGAGE TALENTED,
INDEPENDENT EARLY STAGE
INVESTIGATORS FROM OUTSIDE THE
CURRENT COLLABORATORY PROGRAM.
THEY WOULD WORK WITH NIH TO
DEVELOP THE SOLICITATION, MANAGE
THE APPLICATION PROCESS AND
ORGANIZE THE REVIEW.
SO WE ENVISION THAT AWARDEES
WOULD RECEIVE UP TO TWO YEARS OF
FUNDING, AND THIS WOULD BE IN
TWO COHORTS, SO YEARS TWO TO
THREE WOULD BE ONE COHORT AND
THEN IN YEARS FOUR TO FIVE,
ANOTHER COHORT WOULD BE
SUPPORTED.
AND WE'RE LOOKING AT DIFFERENT
MODELS TO DEVELOP THIS PROGRAM
AND FOR EXAMPLE, THE CFAR CNIHR
PROGRAM AS WELL AS THE CENTERS
FOR HIV STRUCTURAL BIOLOGY
COLLABORATIVE DEVELOPMENT
AWARDS, JUST AS SOME GREAT
EXAMPLES, AND I WOULD NOTE THAT
ALUMNI OF THE 2013CNIHL PROGRAM
WITH THE CFARs, THIS WAS A
CURE-FOCUSED INITIATIVE IN 2013,
AND ALUMNI FROM THAT PARTICULAR
COHORT ARE NOW ESTABLISHED CURE
INVESTIGATORS, INCLUDING
DR. NDHLOVU, WHO'S ON OUR
COUNCIL TODAY.
SO JUST WANTED TO POINT THAT
OUT.
ALL RIGHT.
SO WE FEEL THAT A COORDINATION
CENTER WOULD BE IMPORTANT TO
ENHANCE SYNERGY AND
COLLABORATION ACROSS THE
COLLABORATORY PROGRAM,
PARTICULARLY IF THE PROGRAMS ARE
MORE SPECIALIZED THAN THE
CURRENT BROADER APPROACHES.
AND BY SUPPORTING STRATEGIC
COMMUNICATIONS, LEVERAGING
COMPLEMENTARY STRENGTHS AND
FACILITATING TEAM SCIENCE, THE
COLLABORATORIES CAN WORK
TOGETHER TO ADVANCE PROMISING
CLINICAL STRATEGIES FOR HIV
CURE.
SO WE ARE VERY THANKFUL FOR THE
EXCELLENT DISCUSSION FROM ALL OF
THE REVIEWERS FROM THE PREVIOUS
TWO PARTS OF THE CONCEPT.
SO THEY FELT THAT A COORDINATION
CENTER WOULD BE VALUABLE TO
INCREASE SYNERGY, REDUCE
ADMINISTRATIVE BURDEN AND
PROVIDE A SPACE FOR SHARING AND
COLLECTIVE SCIENTIFIC PROBLEM
SOLVING ACROSS THE PROGRAM, AND
THEY NOTED THAT HANC IS AN
EXCELLENT EXAMPLE OF THE ABILITY
TO BUILD WORKING GROUPS AS
NEEDED AS VALUABLE RESOURCES FOR
THE PROGRAM.
THE REVIEWERS FELT THAT ROLES
AND RESPONSIBILITIES NEEDED TO
BE CAREFULLY DELINEATED TO MAKE
SURE THAT THE COORDINATION
CENTER COULD ADD VALUE AND MEET
COLLABORATORY NEEDS WITHOUT
CREATING UNDUE BURDEN THAT WOULD
SLOW PROGRESS.
SO WE COMPLETELY AGREE AND WILL
PLAN TO CAREFULLY DEFINE THESE
ROLES AND EXPECTATIONS.
AND I WOULD NOTE THAT BECAUSE OF
THE COOPERATIVE AGREEMENT
MECHANISM, DAIDS STAFF WILL BE
DIRECTLY INVOLVED IN THE
COORDINATION CENTER AND WILL
CONTINUOUSLY EVALUATE AND ADJUST
AS NEEDED.
THERE WAS A CONCERN OF
POTENTIALLY CONFLICTING FEEDBACK
FROM THE CROSS MDC ADVISORS AND
INDIVIDUAL SCIENTIFIC ADVISORY
BOARDS, SO WE'VE TRIED TO
CLARIFY IN THE PRESENTATION THAT
THE COORDINATING -- COORDINATION
CENTER SCIENTIFIC CONSULTANTS
WILL PROVIDE FEEDBACK ON THE
PROGRAM AS A WHOLE AND WOULD NOT
SUPERSEDE THE VERY VALUABLE
FEEDBACK FROM THE INDIVIDUAL
COLLABORATORY SCIENTIFIC
ADVISORY BOARDS.
AND FINALLY, THE REVIEWERS FELT
THAT A FORMAL PROGRAM TO ENGAGE
AND SUPPORT EARLY STAGE
INVESTIGATORS WAS VERY MUCH
NEEDED, AND THEY WANTED
ADDITIONAL DETAILS TO CLARIFY
HOW THE PROGRAM WOULD WORK.
SO I TRIED TO INCORPORATE THAT
INTO THE PRESENTATION, AND WOULD
NOTE THAT DAIDS WILL BE WORKING
WITH THE COORDINATION CENTER TO
FINALIZE THE REMAINING DETAILS.
HAPPY TO TAKE QUESTIONS AND
TANIA CAN COME UP AS WELL AND
ANY QUESTIONS ON THE FIRST -- I
GUESS THE COORDINATION CENTER
AND THEN ANY REMAINING QUESTIONS
FROM THE PROGRAM AS A WHOLE.
>> WE HAVE A QUESTION ONLINE.
DR. DERDEYN.
>> HI.
THIS IS CINDY DERDEYN AGAIN IN
SEATTLE.
THIS DOES SOUND LIKE A REALLY
GREAT IDEA.
MY QUESTION IS, I GUESS THIS
WOULD -- THERE WOULD BE A P.I.
OR SOMEONE, YOU KNOW, AN
APPLICATION.
WOULD THAT PERSON HAVE TO BE A
PERSON WHO DOESN'T HAVE A
COLLABORATORY OR WOULD YOU BE
ABLE TO BE P.I. OF A
COLLABORATORY AND THE
COORDINATING CENTER?
I WAS KIND OF UNCLEAR ON HOW
THAT WOULD WORK.
>> AT THIS POINT, WE CERTAINLY
ANTICIPATE THAT THERE WOULD BE
OPPORTUNITIES FOR PIs WHO ARE
COLLABORATING OR INVOLVED IN ONE
OR MORE INDIVIDUAL
COLLABORATORIES, BUT THE
COORDINATION CENTER WOULD NEED
TO BE A NEUTRAL -- A NEUTRAL
BODY TO MAKE SURE THAT NO ONE
PARTICULAR COLLABORATORY WAS
GETTING SPECIAL TREATMENT, FOR
EXAMPLE, SO AT THIS POINT, I
WOULD SAY THAT IT WOULD BE
UNLIKELY THAT WE WOULD ALLOW THE
SAME PI FOR A COLLABORATORY AND
COORDINATION CENTER.
RIGHT NOW WE DON'T ALLOW THE
SAME PI TO APPLY FOR BOTH THE
PEDIATRIC AND THE ADULT
COLLABORATORY.
SO -- DOES THAT HELP?
>> YEAH, THAT HELPS A LOT, AND
IT MAKES SENSE THAT YOU MIGHT
WANT TO BE A PERSON WHO IS
SOMEWHAT NEUTRAL.
SO THAT MAKES A LOT OF SENSE.
THANK YOU FOR THE CLARIFICATION.
>> THE PRIMARY ROLE FOR THIS IS
ADMINISTRATIVE, BUT CLEARLY,
THERE ALSO WOULD NEED TO BE
ENOUGH SCIENTIFIC BACKGROUND BY
COORDINATION CENTER STAFF BUT
CERTAINLY THERE COULD BE
OPPORTUNITIES TO BE INVOLVED IN
MULTIPLE COLLABORATORIES, BUT
THE P.I. OF THE COORDINATION
CENTER WOULD HAVE A VERY
DIFFERENT ROLE THAN THE P.I. OF
A --
>> IT'S GREA TO SEE -- ON MERITS
OF THE PROGRAM.
MY QUESTION WAS DIRECTED ON THE
JUNIOR INVESTIGATORS IN THAT
PROGRAM.
YOU MENTIONED THEY WERE LIKELY
GOING TO BE FROM OUTSIDE OF THE
COLLABORATORIES OR IS IT OPEN TO
BOTH?
AND AS A FOLLOW-UP QUESTION,
LOOKING BACK AT THE CNIHR
PROGRAM, WE DID HAVE MENTORS
ATTACHED TO THAT PROGRAM, I
WASN'T SURE IF THAT WAS BEING
DISCUSSED OR ADJUDICATED.
>> YES, I THINK GENERALLY THE
IDEA IS TO BRING IN NEW IDEAS,
NEW MORE JUNIOR INVESTIGATORS
WHO WE THINK IT WOULD PROBABLY
WORK BETTER TO HAVE THEM BE
ALREADY INDEPENDENT SO THAT
THEY'RE NOT GETTING CONFLICTING
ADVICE FROM THEIR OWN MENTORS
VERSUS SOMEONE FROM THE
COLLABORATORY, BUT YES, I THINK
THE IDEA WOULD BE TO INCORPORATE
SOME SORT OF SCIENTIFIC
COLLABORATION AND MENTORSHIP
WITH THE COLLABORATORY, SO THE
IDEA IS TO SORT OF BRING THEM IN
TO ONE OR MORE COLLABORATORIES,
AND GET THEM ENGAGED.
I THINK THERE ARE DIFFERENT
MODELS THAT WE'RE CONSIDERING SO
THE SENIOR PROGRAM, FOR EXAMPLE,
IS A TWO-PHASE PROCESS WHERE THE
FIRST PHASE IS CONCEPTUAL AND
THE SECOND PHASE INVOLVES
WORKING WITH A SPECIFIC CFAR
INVESTIGATOR TO WRITE THE
APPLICATION BASICALLY.
SO THAT'S ONE MODEL, THERE ARE
OTHER WAYS TO DO IT, SO WE'RE
DEFINITELY LOOKING AT DIFFERENT
OPPORTUNITIES.
BUT THE OVERALL IDEA IS TO BRING
PEOPLE IN WHO NORMALLY WOULD
MAYBE NOT HAVE AS MUCH
CONNECTION WITH THE PROGRAM.
>> OTHER QUESTIONS?
>> A GENERAL QUESTION.
SO YOU HAVE 300 OF THE TOP LABS
IN THIS NOW WHO ARE GOING TO
HAVE A COORDINATING CENTER,
WHICH IS GREAT, AND YOU
OBVIOUSLY WANT TO HAVE AS MANY
NEW PEOPLE ENTERING THE FIELD AS
POSSIBLE, SO I'D LOVE TO HEAR
WHAT YOUR NEW THOUGHTS ARE IN
TERMS OF REALLY JUST FINDING
NON-CONFLICTED QUALIFIED
REVIEWERS FOR THIS, WHICH I KNOW
HAS BEEN AN ONGOING CHALLENGE.
>> FOR THE PROGRAM AS A WHOLE OR
FOR THE COORDINATION CENTER?
>> FOR THE PROGRAM AS A WHOLE.
>> RIGHT.
YEAH, THAT'S AN EXCELLENT POINT.
I THINK THEY'RE OUT THERE.
I THINK WE HAVE TO LOOK AT THE
FUNCTION OF THE ENTIRE PROGRAM
AND THAT'S AN EXCELLENT
CONSIDERATION.
I KNOW I'M INVOLVED IN A
DP2 PROGRAM, WHICH IS
NIAID-WIDE, THERE'S ALSO AN NIH
VERSION, SO FINDING REVIEWERS TO
ADDRESS THE BROADER GOALS AND
CONCEPTS ASSOCIATED WITH THE
APPLICATIONS IS IMPORTANT,
AND -- BUT I THINK WE DEFINITELY
RECOGNIZE THAT THAT'S A CRITICAL
NEED FOR HAVING A FAIR AND -- A
FAIR REVIEW WITH APPROPRIATE
EXPERTISE FOR SURE.
>> I SEE RAPHI HAS A QUESTION.
>> JUST AN EXHORTATION AS THE
U01 COORDINATING CENTER
SOLICITATION IS CRAFTED, JUST TO
BE CLEAR ABOUT THE SCOPE OF THE
COORDINATING CENTER.
AND I JUST BRING THAT UP KNOWING
THAT BOTH THE THERAPEUTICS AND
THE PREVENTION NETWORKS WITH
WHICH THE MDC'S REPORTS ARE
COLLABORATING OR PROMISING
INTERVENTIONS TO GO INTO
CLINICAL TRIALS APPROPRIATELY
FIREWALLING LARGELY THOSE TWO
ACTIVITIES, BULL THE ISSUES OF
RISKS TO PARTNERS WHEN TREATMENT
INTERRUPTIONS ARE ASSOCIATED
WITH SOME OF THESE CURE
STRATEGIES, WOULD THAT FALL
WITHIN THE SCOPE OF THIS
COORDINATING CENTER TO HELP
THINK ABOUT OR WOULD THAT BE
RELEGATED TO, FOR EXAMPLE, HANK
OR ANOTHER GROUP?
I THINK JUST BEING CLEAR ABOUT
THAT WOULD BE HELPFUL IN NOT
HAVING CONFLICTING PARALLEL
INITIATIVES.
>> SO I'M NOT SURE -- AS FAR AS
WOULD THAT SPECIFIC TOPIC BE
PART OF THE COMMUNITY?
OR PART OF THE SCIENTIFIC
OBJECTIVES?
I WASN'T CLEAR EXACTLY.
>> I GUESS WHATEVER IS DECIDED
INTERNALLY, WHETHER OR NOT
THERE'S OVERLAP WITH HANC OR
NOT, JUST TO BE CLEAR ABOUT
WHETHER OR NOT THAT DOMAIN WOULD
FALL WITHIN THIS SOLICITATION
AND THE SCOPE OF THIS PROPOSED
COORDINATING CENTER OR NOT, JUST
SO PROPOSING GROUPS COULD
ADDRESS THAT OR NOT
APPROPRIATELY.
>> RIGHT.
WELL, I THINK CERTAINLY -- SO
ONE ROLE FOR THE COORDINATION
CENTER WOULD BE TO HELP THE
INDIVIDUAL COLLABORATORIES
ADDRESS SPECIFIC ISSUES RELATED
TO THE TYPES OF STRATEGIES THAT
THEY'RE DEVELOPING.
SO -- BUT AS FAR AS OVERLAP, I
THINK WE CERTAINLY COULD BE
WORKING WITH HANC, BUT AS FAR AS
THE OVERLAP, YEAH, I DON'T THINK
THE -- WE DEFINITELY WOULD BE
CONSIDERING THE ROLE FOR HANC AS
A COMPLEMENTARY RESOURCE, SO I
DON'T THINK WE WOULD BE
ADDRESSING THAT DIRECTLY.
>> I THINK BECAUSE OF THE FOCUS
OF THE COLLABORATORIES, WE
THOUGHT MOSTLY ABOUT THE
ACCEPTABILITY OF THE STRATEGIES
BEING DEVELOPED AND SO FORTH.
AND THE CLINICAL GROUPS WOULD BE
MOSTLY FOCUSED AROUND TREATMENT
INTERRUPTION, BUT TO BRING THOSE
COMMUNITY GROUPS TOGETHER, TO
HAVE THAT DIALOGUE TOGETHER AND
WORK TOGETHER SO THERE'S A
SEAMLESS HANDOFF FROM ONE TO THE
OTHER.
SO I THINK IT'S A GREAT IDEA,
AND I THINK THAT'S WHERE THE
COORDINATING CENTER COULD REALLY
HELP.
>> RIGHT, BRINGING IN THOSE
TYPES OF CONSUL TAIGS I THINK
WOULD BE EXCELLENT.
>> I CAN JUST ADD THAT ONE OF MY
GOALS IN SUGGESTING HA NC AS A
BODY FOR YOU ALL TO WORK WITH
WAS SO THAT YOU DON'T HAVE TO
START FROM SCRATCH, BECAUSE HANC
HAS A LOT OF INFRASTRUCTURE
ALREADY IN PLACE AND SO IF YOU
CAN'T USE THE INFRASTRUCTURE,
MAYBE CULLING IDEAS ABOUT HOW TO
CREATE THAT INFRASTRUCTURE SO
YOU CAN KIND OF GET THE BALL
ROLLING OUT THE GATE.
>> RIGHT, RIGHT.
THANK YOU VERY MUCH.
>> DO YOU JUST WANT TO INTRODUCE
YOURSELF AS WE FINISH UP?
>> I'M SORRY.
I'M LOUIS SHACKELFORD, HE/HIM
PROGRAMS, THE VACCINE TRIALS
NETWORK BASED OUT OF FRED
HUTCHINS, SEATTLE, WASHINGTON.
>> THANK YOU.
OKAY.
I THINK WE'VE ADDRESSED ALL OF
THE QUESTIONS.
I WANT TO THANK YOU BOTH FOR THE
PRESENTATIONS.
AND ASK ALL THE VOTING MEMBERS
TO PLACE THEIR VOTES.
IN THE MEANTIME, I'LL INVITE
CAROLYN WILLIAMS TO THE PODIUM
TO TELL US ABOUT THAT IDEA.
>> IS EVERYONE THROUGH VOTING?
I DON'T WANT TO -- ALL RIGHT.
I'M CARLY WILLIAMS, TODAY I'D
LIKE TO PRESENT TO YOU A LIMITED
COMPETITION FOR THE
INTERNATIONAL EPI DATABASES TO
EVALUATE AIDS PROGRAM, WHICH
BRINGS TOGETHER EPIDEMIOLOGY
SCIENCE ACROSS MANY INSTITUTES
AT THE NIH TO STUDY THE IMPACT
OF THE HIV EPIDEMIC AND THE
TREATMENT OF HIV GLOBALLY.
IT'S A LIMITED COMPETITION.
IT WILL BE A U01 AS IT HAS BEEN
BEFORE, A COOPERATIVE AGREEMENT.
THIS IS A REISSUE FOR FIVE YEARS
WITH NIAID'S CONTRIBUTION AT
$9.2 MILLION.
AS YOU CAN SEE, WE'VE HAD MANY
INSTITUTES THAT HAVE CO-FUNDED
WITH US IN THE PAST, AND HAVE
EXPRESSED AN INTEREST TO
CONTINUE WITH US AS WELL AS
MAYBE BRINGING IN SOME OTHER
INSTITUTES.
SO THIS INCLUDES 44 COUNTRIES
AND 388 CLINICAL SITES.
WE HAVE MORE THAN 2 MILLION
PEOPLE LIVING WITH HIV WHO HAVE
CONTRIBUTED DATA TO THE DATABASE
WITH ABOUT 200,000 CHILDREN BOTH
WITH HIV AND EXPOSED TO HIV
DURING PREGNANCY.
THE PROGRAM SUPPORTS THE
COLLECTION OF DATA AT THE
CLINICAL LEVEL FROM CLINICS THAT
RANGE FROM SMALL RURAL
FACILITIES TO LARGE TERTIARY
CARE HOSPITALS ACROSS THESE
REGIONS.
AND THEY CONDUCT RESEARCH AT THE
CLINIC LEVEL AND AT THE REGIONAL
LEVEL, AS WELL AS ACROSS THE
COUNTRY, THE PROJECT INVOLVES
BRINGING ALONG RESEARCHERS
WITHIN THE PROGRAM, INVITING OUT
TO OTHER INVESTIGATORS, AND IT
CAN SERVE AS A PLATFORM FOR
OTHER RESEARCH PROJECTS.
SO IEDEA IS VERY MUCH A DATA
SCIENCE PROGRAM.
IT SITS NEXT TO AN R24 GRANT
CALLED HA HARMONIST WITH A SUITF
SOFTWARE THAT REALLY HELPS US
DAYS TAKE DATA FROM THE CLINIC,
WHICH THEN GOES TO A REGIONAL
DATASET, IT GOES THROUGH A SET
OF SOFTWARE PROGRAMS TO
STANDARDIZE IT, BRINGING IT INTO
THE IEDEA DATA STANDARD,
EVALUATE THE QUALITY OF THAT
DATA AND THEN BRING THAT BACK TO
THE CLINIC TO IMPROVE THE
QUALITY OF DATA, ENGAGE WITH THE
INVESTIGATORS IN THE FIELD, WHY
DOES THE DATA LOOK LIKE THIS,
WHY IS THIS MISSING, WHY IS
THAT -- TO CREATE DATASETS THAT
ARE ACCURATE REPRESENTATIONS OF
WHAT IS IN THE CLINIC DATASET,
WHICH CAN THEN BE USED FOR A
SPECIFIC ANALYSIS.
SOMETIMES THEY'RE USED FOR
GLOBAL DATASETS.
WE HAVE NOW A MULTIUSE DATASET
THAT IS A MORE STATIC DATASET
THAT'S A LITTLE BIT FASTER FOR
PEOPLE TO ACCESS, AND THEN MOVE
INTO ANALYSES.
OF COURSE A CONSORTIUM THIS BIG
IS REALLY ALL ABOUT NETWORKING.
AND ABOUT HOW WE BRING PEOPLE
TOGETHER.
WHEN WE STARTED THIS PROGRAM,
ONE OF THE ELEMENTS WE TRIED TO
PUSH OUT WAS A CONCEPT OF
CULTURES OF TRUST IN WHICH
PEOPLE ARE WORKING WITH EACH
OTHER WITH A VERY WELL-DEFINED
SET OF RESEARCH PROCEDURES,
MANAGEMENT OF DATA, AND
ADHERENCE TO THE CONCEPT OF THE
NETWORK.
SO THE ANALYSES CAN BE CONDUCTED
WITHIN THE COHORT, MAYBE THEY
ARE A BI- OR TRI-REGIONAL
PROJECT WORKING TOGETHER, THE
COHORT STUDY DATA ON ADOLESCENTS
AND YOUNG ADULTS.
THE SENTINEL RESEARCH, PERSONS
OVER 40 YEARS OLD, OR THE TBSRN,
WHICH IS SPECIFIC DATA THAT ARE
COLLECTED TO ADDRESS SOME GAPS
IN DATA THAT WE'VE IDENTIFIED
OVER THE COURSE OF IEDEA.
THE REGIONS ALL COLLABORATE
TOGETHER TO DO THE WORK OF
RUNNING A CONSORTIUM LIKE THIS,
SO ONE REGION MAY BE HANDLING
THE MEETINGS, ONE REGION MAY BE
WORKING WITH THE CALLS IN
BETWEEN, SO THE WORK IS
DISTRIBUTED OUT ACROSS THE
REGION.
AS I MENTIONED, THERE'S ALSO
COLLABORATIONS OUTSIDE OF THE
CONSORTIUM WITH, SAY, THE WHO,
UND AIDS OR PEPFAR ENTITIES.
THE CONSORTIUM IS VERY WELL
ESTABLISHED NOW AND HAS A PRETTY
STANDARD RATE OF PRODUCTION OF
PAPERS, IN EACH CYCLE THEY'VE
PRODUCED OVER A THOUSAND PAPERS
IN THE LAST TWO ROUNDS OF
INVESTIGATIONS, AND YOU CAN SEE
MANY ARE AT THE REGIONAL LEVEL,
WITH A FEW THAT ARE
MULTIREGIONAL PAPERS.
TO DESCRIBE THE BREADTH OF
RESEARCH IN IEDEA IS QUITE
DIFFICULT AND I ENCOURAGE PEOPLE
WHO ARE INTERESTED TO GO TO THE
WEBSITE AT IEDEA.ORG AND YOU CAN
SEE THE FULL LIST OF
PUBLICATIONS FROM THE GROUP.
BUT THERE HAVE BEEN BIG PAPERS
THAT HAVE COME OUT OVER THE LAST
MANY YEARS.
THE WHEN TO START PAPERS FROM
THE CONSORTIUM AROUND 2007, I
BELIEVE THAT PAPER WAS
PUBLISHED, LOOKING AT LOST TO
FOLLOW-UP, SOME RESEARCH ON
CANCER AND CARDIOVASCULAR
OUTCOMES, EACH OF WHICH
CONTRIBUTE AT THE REGIONAL AND
GLOBAL LEVEL.
BECAUSE WE SIT WITHIN REGIONS
AND SUPPORT THE INVESTIGATORS
WITHIN THOSE REGIONS, IT'S A
FANTASTIC PLACE TO GET YOUR
ADVANCED DEGREE.
WE'VE HAD A LOT OF INVESTIGATORS
WHO'VE MOVED THROUGH THE RAM IN
EACH OF THE REGIONS, AND
ACHIEVING UPPER LEVEL DESCREES,
WHETHER THEY'RE MASTER'S,
DOCTORAL, EARLY STAGE OR --
ACHIEVEMENTS.
THE P.I. RECEIVED HER PH.D. US
USING IEDEA DATA.
THIS WINTER, THERE WAS DATA ON
DOLUTEGRAVIR SO I WANTED TO TALK
ABOUT THE THINGS IEDEA DOES IN
THE AREA WHICH I THINK IS REALLY
INTERESTING WHICH IS MODELING
AND USING THIS BIG DATA
STRUCTURE TO ANSWER SOME
FUNDAMENTAL QUESTIONS.
ONE OF THE BIGGEST QUESTIONS FOR
COUNTRIES IS FORECASTING THEIR
NEEDS AND UNDERSTANDING THE
POPULATIONS OF PEOPLE WHO ARE
INFECTED WITH HIV WITHIN THE
COMMUNITY, AND A QUESTION AROSE
ABOUT HOW MANY CHILDREN ARE
THERE WHO ARE HIV INFECTED.
SO WORKING WITH THE SPECTRUM
TEAM ON THEIR PEDIATRIC SPECTRUM
MODEL, IEDEA CONTRIBUTED NEW
PARAMETERS FOR THAT MODEL, AND
IT SHOWED A NUMBER OF THINGS.
ONE WAS, FEWER CHILDREN WERE
ACTUALLY GETTING INFECTED
PERINATALLY.
SO THERE WAS A LOWER NUMBER OF
CHILDREN WHO WERE INITIALLY
INFECTED, BUT UNFORTUNATELY
AMONG THOSE CHILDREN WHO WERE
INFECTED, THEY WERE STARTING
CARE LATER THAN HAD BEEN
ANTICIPATED, SO MORTALITY RATES
WHY ACTUALLY HIGHER IN THOSE
CHILDREN THAN WE HAD
ANTICIPATED.
AND THOSE TWO ELEMENTS COMBINED
TOGETHER MEAN THAT THERE ARE
MANY FEWER CHILDREN LIVING WITH
HIV TODAY.
27% LOWER, A THIRD LOWER.
SO A BIG SHIFT IN OUR
UNDERSTANDING ABOUT WHERE THE
EPIDEMIC IS AND HOW TO
ANTICIPATE AND FORECAST NEEDS.
ANOTHER AREA WHERE IT'S BEEN
ABLE TO CONTRIBUTE IS LOOKING AT
THE U.S. AND LOOKING AT THE HIV
EPIDEMIC.
IN THE TOP GRAPH HERE WE SEE
THREE TIMES 2010, 2020 AND 2030.
THIS IS THE PROPORTION OF ALL
PEOPLE WHO HAVE HIV.
SO IN 2010, WE SEE THAT WE HAVE
THIS PRETTY SIMPLE CURVE HERE,
NORMAL DISTRIBUTION OF HIV
INFECTION.
THE MEDIAN AGE OF PEOPLE WHO
HAVE HIV IS ABOUT 46 YEARS IN
THE UNITED STATES.
AND OVER TIME, THESE CURVES SEEM
TO BE SHIFTING OVER TO OLDER AGE
GROUPS, WHICH MAKES SENSE AS WE
HAVE THERAPY.
UNFORTUNATELY, THOUGH, WE ALSO
HAVE A NEW GROUP OF PEOPLE WHO
ARE INFECTED WHO BECOME A PARENT
IN 2020 AND REMAIN IN 2030.
THESE ARE NEW YOUNG INFECTIONS
ANTICIPATED TO OCCUR.
IF THERE IS NO PROGRESS ON THE
INITIATIVE.
BUT IF WE ARE SUCCESSFUL WITH
THE MB HIV EPIDEMIC, WE SEE THE
CURVE MOVES OVER TOWARD THE
RIGHT WITH PEOPLE AGING, BUT
WITHOUT, THIS GROUP HERE, THIS
LARGER GROUP OF YOUNG PEOPLE
GETTING INFECTED.
SO YOU CAN SEE THAT THIS BUMP IS
WIDER AND BIGGER THAN THIS BUMP,
WHICH IS NOW LEAVING WITH MORE
YOUNG PEOPLE NOT INFECTED.
SO A HOPEFUL LOOK FOR THE 2013.
WE SEE HERE WITHOUT THE SUCCESS
OF THE PROGRAM, 54,000 PEOPLE
UNDER 30 INFECTED WITH HIV,
WHEREAS WITH SUCCESS IN THE
PROGRAM, ONLY 16,000.
SO THESE ARE THE KIND OF
SUBSTANTIVE PROGRESS THAT WE
SHOULD HOPE TO BE ABLE TO SEE IF
IT'S SUCCESSFUL, BUT THEN WE
ALSO HAVE TO NOTE THAT THE
PREVALENCE OF THE EPIDEMIC, THE
NUMBER OF PEOPLE WHO REMAIN
HIV-INFECTED WILL CONTINUE, AND
WE WILL CONTINUE TO HAVE A
NUMBER OF PEOPLE WITH LONG-TERM
COMORBIDITIES ASSOCIATED WITH
THEIR HIV INFECTION.
BECAUSE THIS IS A LARGE PROGRAM
AND WE'RE RECOMPETING IT AGAIN
FOR THE FIFTH TIME, WE ASKED FOR
AN EXTERNAL EVALUATION OF THE
PROGRAM WHICH WAS CONDUCTED BY A
CONTRACTING GROUP.
AND THEY INTERVIEWED OTHER
PROGRAM OFFICERS ACROSS THE NIH
ABOUT THEIR INTERACTION WITH THE
PROGRAM AS WELL AS MEMBERS OF
THE WHO TEAM, WHO USE THE DATA.
AND THE RESULTS OF THIS
EVALUATION WERE QUITE FAVORABLE.
IEDEA IS SEEN AS A HIGHLY
SUCCESSFUL PROGRAM THAT IS
CRITICAL FOR GLOBAL HEALTH.
THIS CONFLICT THAT WE HAVE
BETWEEN BEING A LARGE COHORT
STUDY THAT FOLLOWS MILLIONS OF
PATIENTS VERSUS HAVING THESE
SUBCOHORTS OF THE SENTINEL
RESEARCH NETWORK, THE SMALL
COHORTS SEEM TO BE PLAYING A
ROLE, THE TRAINING HAS BEEN
IMPACTFUL, THERE WAS A BIG
CONFLICT BETWEEN OUR HOPE TO
EXPAND AND TO INCLUDE ADDITIONAL
QUESTIONS BUT YET WANTING TO
MAINTAIN OUR FOCUS, THE OPINION
OF REVIEWERS IS QUITE MIXED ON
THE ADDITION OF CLINICAL TRIALS
TO THE PROJECT AND YOU'LL NOTICE
THAT THIS INITIATIVE IS GOING
OUT WITHOUT CLINICAL TRIALS.
THE LIMITATIONS TO THE PROGRAM
WERE PERCEIVED TO BE MOSTLY
FINANCIAL, THAT IF THERE WAS
MORE FUNDING, THERE COULD BE
MORE SCIENCE.
SO IS WE'RE BUYING WHAT WE GET.
THERE WERE NOT ANY SUGGESTIONS
OF ANY AREAS OF THE CONSORTIUM
THAT WE SHOULD DISCONTINUE.
IT WAS FELT THAT WE SHOULD ALLOW
THINGS TO MOVE NATURALLY IF
SOMETHING WERE TO BE NOT
WORTHWHILE IN THE FUTURE, IT
COULD JUST DROP OUT, BUT AT THIS
TIME, THERE WAS NO NEED FOR
NIAID TO ASK FOR
DISCONTINUATION.
SO WE'RE MAINTAINING A LOT OF
THE FUNDAMENTAL STRUCTURE OF
IDEA FROM ROUND FOUR TO ROUND
FIVE.
THE SENTINEL RESEARCH NETWORKS
ASSISTED BY NIDDK AND AAA,
HEART, LUNG AND BLOOD, MENTAL
HEALTH, THOSE COHORTS WILL
CONTINUE THE
TUBERCULOSIS-SPECIFIC SRN WILL
CONTINUE, THE WORK OF THE
NATIONAL CANCER INSTITUTE, THE
SPECIFIC WORK THAT THEY DO
LINKING TO REGISTRIES AND
IMPROVING CANCER DIAGNOSIS WILL
CONTINUE, STUDY THES OF PREGNANT
WOMEN AND UNEXPOSE AND INFECTED
CHILDREN ALSO.
THE FAMILY CYST ON DATA SCIENCE
AND THE WORK WITH THE NATIONAL
LIBRARY OF MEDICINE TO INCREASE
THE FAIRNESS OF OUR DATA,
FINDABLE, ACCESSIBLE, PUSHING TO
INCLUDE THAT DATA IN THE NIAID
DATA ECOSYSTEM, WORKING TO
DEVELOP EVER BETTER DATA
VISUALIZATION SO THAT THE
RESULTS OF THE STUDY ARE CLEAR
TO ALL POPULATIONS, AND THEN
MAINTAINING THE FOGARTY LINKS
FOR OUR TRAINING PROGRAMS AND
THEIR LINKAGE WITH THEIR VERY
STRONG D43 PROGRAM, AS WELL AS A
NEED TO SUPPORT EARLY STAGE
INVESTIGATORS, PEOPLE AFTER
THEIR INITIAL TRAINING, AND
NEEDING SUPPORT TO BE ABLE TO
MAINTAIN THEIR WORK IN RESEARCH.
CHANGES FROM FOUR TO FIVE, IT'S
REALLY MORE JUST A -- I DON'T
KNOW IF THE WORD CHANGE IS
APPROPRIATE HERE, BUT WE WILL
CONTINUE TO COLLECT DATA TO
IMPROVE GAPS IN DATA COLLECTION,
PARTICULARLY AS WE ALL KNOW THAT
PEPFAR IS IN A MOMENT OF
TRANSITION OR UNCERTAINTY, AND
BEING SURE THAT IDEA IS ABLE TO
CONTINUE TO SERVE THE RESEARCH
AGENDA EVEN WITH THESE
UNCERTAINTIES WITH PEPFAR.
THINGS LIKE THE COLLECTION OF
CD4 AND VIRAL LOADS, DATA ON
DRUG RESISTANCE.
THESE ARE THINGSING THAT ARE NOT
OFTEN AVAILABLE INTERNATIONALLY
AND IDEA WILL BE THERE TO FILL
THOSE GAPS.
REALLY LIKE TO INCREASE THE
EMPHASIS ON DATA LINKAGES TO
OTHER DATA SOURCES, THE CANCER
REGISTRY, THE DEATH REGISTRY,
UNDERSTANDING HOW PEOPLE ARE
MOVING AROUND WITHIN A COMMUNITY
AND CHANGING HEALTHCARE
SETTINGS.
WORKING ON THE CREATION OF THE
MULTIUSE DATASET, WHICH IS THIS
THIS STANDING DATASET I
MENTIONED THAT WILL ACCELERATE
THE WAY THAT IDEA IS ABLE TO GET
DATA TO INVESTIGATORS, THE
STANDING DATASET WILL EXIST.
EXPANDING SUPPORT AND TRAINING
FOR MID CAREER INVESTIGATORS.
AND THEN TO CONTINUE TO PUSH AND
TO SUPPORT IEDEA INVESTIGATORS
TO GET ANCILLARY GRANT FUNDING,
NIH GRANTS AREN'T EASY TO GET,
AND ANY HELP THAT WE CAN GIVE TO
IMPROVE THEIR WORK IN THAT AREA.
WE HAD DR. ELAINE ABRAMS AND
RAPHI LIND V LI LANDOVITZ.
THEY WERE VERY PLEASED TO SEE
THE SUCCESS OF TRAINING YOUNG
INVESTIGATORS.
THERE WAS SOME CONCERN ABOUT THE
R24, THE HARMNIST DATA SCIENCE
PROGRAM, THAT IT IS SUCH AN
IMPORTANT PART OF THE GROUP BUT
ACTUALLY FUNDED OUTSIDE OF
IEDEA.
HARMNIST WORKS FOR OTHER PEOPLE
AS WELL.
THEY ARE CRUCIAL TO IEDEA BUT
THEY ALSO SUPPORT SOME OTHER
PROGRAMS SO THEY AREN'T JUST AN
INSIDE IEDEA GROUP.
THERE WAS CONCERN ABOUT HOW
COULD WE CONTINUE TO EVALUATE
CARE IN THIS UNCERTAIN GLOBAL
FUNDING ENVIRONMENT.
I THINK WE NEED TO RELY ON THE U
COOPERATIVE AGREEMENT MECHANISM
TO BE ABLE TO BE FLEXIBLE TO
FIGURE OUT WHERE WE MAY OR MAY
NOT NEED TO MAKE CHANGES IF
THERE ARE SUBSTANTIAL
UNCERTAINTIES.
THE REVIEWERS WERE EAGER TO SEE
IEDEA STAY FOCUSED ON THE LARGE
DATA SCIENCE.
THEY AGREED THAT CLINICAL TRIALS
WERE NOT A GOOD DIRECTION FOR
THE PROGRAM TO CONSIDER GOING,
AND WE WILL BE SURE THAT THAT'S
WELL EXPRESSED AND DESCRIBED IN
THE NOFO.
THERE WAS SOME CONCERN ABOUT THE
SPEED AT WHICH IDEA CAN MOVE.
IT IS A VERY LARGE GROUP, MOVING
DATA MORE RAPIDLY, GETTING
RESULTS OUT MORE QUICKLY.
I THINK NOW IN THE POST-COVID
WORLD, THE ROLE OF
PREPUBLICATION RELEASE OF
INFORMATION, I WAS THINKING
ABOUT THAT AFTER WE TALKED TO
THE REVIEWERS, AND WAYS IN WHICH
WE CAN COMMUNICATE RESULTS IN
OTHER WAYS.
IT ALSO WILL REQUIRE, AGAIN,
MORE EMPHASIS ON THIS DATA
SCIENCE TO REALLY ACCELERATE THE
MOVEMENT OF DATA.
THERE WERE SOME QUESTIONS FROM
THE REVIEWERS ABOUT BEING ABLE
TO EXPAND INTO AREAS WHICH WE
NOW SEE AS SO IMPORTANT,
INCLUDING PREP AND STI
EPIDEMIOLOGY AND CARE.
I THINK THIS AGAIN EMPHASIZES
THAT IEDEA IS ALREADY A VERY
WIDE AND BIG PROGRAM, AND
UNDERSTANDING WHERE TO PUT THE
FOCUS, THERE IS A LOT OF
INTEREST FROM THE INVESTIGATORS
TO MOVE INTO THESE AREAS, BUT
RESOURCES MAY NOT BE THERE TO
SUPPORT THAT.
SO THIS IS THE INTERNATIONAL EPI
DATABASES TO EVALUATE AIDS.
AS I MENTIONED IT'S A LIMITED
COMPETITION FOR FIVE YEARS, AND
IT WILL BE A MULTI-IC PROGRAM.
>> THANKS A LOT.
ARE THERE QUESTIONS IN THE ROOM?
SEEMA?
>> THANK YOU, CARLY, THAT WAS A
REALLY NIGHT PRESENTATION,
IMPORTANT WORK, TO SUMMARIZE ALL
OF IT IS HARD, I IMAGINE.
I'M JUST CURIOUS, I'VE BEEN
THINKING A LOT ABOUT GLOBAL
HEALTH EQUITY LATELY, EVEN IN MY
OWN RESEARCH, AND ONE OF THE
THINGS THAT INCREASINGLY IS
COMING UP IS ARE THERE
OPPORTUNITIES FOR PEOPLE BASED
IN LOW AND MIDDLE INCOME
COUNTRIES TO DIRECT RESEARCH
PRIORITIES AND TO HAVE
OPPORTUNITIES TO BE FIRST AND
SENIOR AUTHORS, AND I WASN'T
SURE IF THE EXTERNAL REVIEW
LOOKED AT THAT, IF YOU HAVE AN
OPPORTUNITY TO LOOK AT THE
PUBLICATIONS THAT HAVE COME OUT
OF THIS, HOW OFTEN DOES THAT
HAPPEN?
AND IT MIGHT BE SOMETHING TO
THINK ABOUT, MAYBE NOT
NECESSARILY EXCLUSIVELY NOW BUT
FOR THE FUTURE?
>> SO THEY DID DO A HUGE REVIEW
OF THE PUBLICATIONS.
ONE OF THE THINGS THEY FOUND IN
DOING A BIG NETWORK ANALYSIS OF
THE PUBLICATION IS REGIONS
PUBLISHED WITHIN REGIONS.
REALLY SOME OF THE ANALYSES THEY
DID WASN'T QUITE AS GRIPPING AS
I HAD HOPED FOR.
FIRST AUTHORSHIP BY SITES IS --
SO ALL DATA BELONG AT THE CLINIC
LEVEL.
WHENEVER AN ANALYSIS IS
REQUESTED, THE REQUEST GOES DOWN
TO THE CLINIC LEVEL AND SAYS DO
YOU WANT TO PARTICIPATE IN THIS
PROJECT.
SO THE INVESTIGATORS AT THAT
SITE ARE IN OR OUT.
ONCE YOU'RE IN ON AN ANALYSIS,
YOU'RE IN.
YOU CAN'T DROP OUT LATER BECAUSE
YOUR CLINIC DOESN'T LOOK GOOD OR
SOMETHING, BUT YOU'RE IN.
AND EACH REGION HAS A CERTAIN
NUMBER OF AUTHORSHIPS ON ANY
MULTIREGIONAL PROJECT TO ENSURE
THAT PEOPLE DOWN ALL THE WAY TO
THE CLINIC LEVEL ARE ABLE TO
PARTICIPATE.
SOME SITES ARE VERY SMALL AND
THEY HAVE A NURSE WHO IS NOT
ENGAGED IN THE SCIENTIFIC
PROJECT, BUT THERE IS A VERY
ACTIVE DEVIER TO PUSH DOWN TO
THE LOCAL LEVEL.
THE FOGARTY MEASUREMENT PROGRAM,
THE FMPERS ARE TWO LUCKY PEOPLE
PER REGION GET PICKED TO BE THE
FMPERS.
THE GOAL IS TO WRITE TWO PAPERS
AND MAKE PRESENTATIONS.
THERE IS MONEY AVAILABLE FOR
THEM TO TRAVEL TO INTERNATIONAL
MEETINGS, AND PEOPLE WHO ARE
ABLE TO GO THROUGH THE FMP
PROGRAM HAVE A GREAT
OPPORTUNITY, BUT AS ALWAYS,
THERE ARE -- MAKING IT POSSIBLE
FOR PEOPLE WHO HAVE TOO MUCH
WORK AT THE CLINIC LEVEL TO
ACTUALLY PARTICIPATE ALSO IN
RESEARCH IS DIFFICULT.
I THINK EVERYONE IS REALLY
COMMITTED TO IT, BUT THE REALITY
OF IT IS DIFFICULT.
I CAN TRY AND LOOK AT FIRST
AUTHORSHIPS, BUT WE TALK ABOUT
IT A LOT.
>> WE PROBABLY HAVE TIME FOR ONE
MORE BRIEF QUESTION AND ANSWER.
ANYONE ONLINE?
ANYONE ELSE IN THE ROOM?
NO?
OKAY.
SO THANK YOU.
I'LL ASK EVERYONE TO PLEASE
VOTE, AND WE WILL TAKE A
15-MINUTE BREAK, AND WE'LL
RECONVENE AT 3:00 P.M.
FOR THE EAST COAST PEOPLE.
AND APPROPRIATE TIME FOR THE
REST OF YOU.
THANKS, EVERYONE.
WE'LL START THE SECOND HALF AND
INTRODUCE STUART SHAPRIO TO
INTRODUCE CHAVDI.
>> HELLO.
I'M STUART SHAPRIO IN THE
VACCINE PROGRAM, THE CONSORTIA
FOR HIV/AIDS VACCINE DEVELOPMENT
AND IMMUNOLOGY.
THE OBJECTIVE OF THIS INITIATIVE
IS TO FUND A COORDINATED
MULTIDISCIPLINARY EFFORT FOCUSED
ON BOTH PRE-CLINICAL HIV VACCINE
DISCOVERY, TRANSLATIONAL VACCINE
DESIGN AND DEVELOPMENT, CLINICAL
VACCINE MANUFACTURE, AND
ULTIMATELY, PROOF OF CONCEPT
THAT OUR INVESTIGATORS CAN
INDUCE BROADLY NEUTRALIZING
ANTIBODIES, OR BNABs, TO AT
LEAST THREE DIFFERENT BNAB
TARGETS, AND ALSO INCLUSION OF
OTHER COOPERATING IMMUNE
RESPONSES.
THIS WILL BE A COOPERATIVE
AGREEMENT.
THIS IS A NEW INITIATIVE, SO
ALTHOUGH IT'S A FOLLOW-ON FROM
THREE PREVIOUS BIG SCIENCE
FUNDING INITIATIVES, THIS IS A
CHANGE SCOPE, SO WE'RE CALLING
IT A NEW INITIATIVE, AND THIS IS
GOING TO BE FOR AWARDS FOR FIVE
YEARS WITH A FIRST-YEAR TOTAL
COST OF $33 MILLION TO FUND TWO
TO THREE AWARDS.
SO I HAVE TO START OFF BY
TELLING YOU HOW WE GOT TO WHERE
WE ARE, AND WHAT OUR GOAL IS
WITH THIS NEW INITIATIVE.
OUR GOAL IS NOT TO DEVELOP THE
VACCINE, BUT RATHER TO DEVELOP
THE UNDERLYING SCIENCE, SO THAT
PHARMA CAN TAKE OVER THE PROCESS
AND DEVELOP VACCINE PRODUCTS AND
THE DIVISION OF AIDS ONLY HAS TO
FUND THE CLINICAL TRIALS NETWORK
TO TEST THOSE PRODUCTS.
THIS IS THE WAY THE TREATMENT
RESEARCH PROGRAM HANDLES
ANTIRETROVIRAL DRUG DEVELOPMENT.
WHERE ARE WE IN THE DEVELOPMENT
OF AN HIV VACCINE THAT
INTRODUCES BROADLY NEUTRALIZING
ANTIBODIES?
WELL, WE'RE ALSO AT THE
DELINEATION OF THE SCIENCE AND
PROOF OF CONCEPT FOR THE
DEVELOPMENT OF A BNAB INDUCING
HIV VACCINE.
HOW DID WE GET HERE?
WE GOT HERE WITH A PORTFOLIO
THAT INCLUDES THREE ITERATIONS
OF BIG SCIENCE FUNDING, CHAVI,
CHAVI-ID AND CHAVD AS WELL AS
MULTIPLE SMALLER GRANT AND
CONTRACT PROGRAMS.
BUT WHAT REMAINS TO BE DONE IS
PROOF OF SON O'CONNOR SEPTEMBER
THAT MULTIPLE BNAB LINEAGES CAN
BE INDUCED, AND WE WANT THEM TO
BE INDUCED IN PHASE ONE CLINICAL
TRIALS OR IN A RIGOROUS ANIMAL
MODEL LIKE NON-HUMAN PRIMATES.
DEFINITION FOR THE RULES FOR
SELECTING PRIMES AND BOOSTS FOR
BNAB INDUCTION, AND ADDITION OF
COOPERATING IMMUNE RESPONSES.
SO WHAT IS REQUESTED IS ANOTHER
FIVE YEARS OF BIG SCIENCE
FUNDING.
SO I HAVE TO EXPLAIN THE ROLE
THAT CHAVD PLAYS IN THE
LANDSCAPE OF HIV VACCINE PROG
PROGRAMS WE HAVE MULTIPLE WAYS
FOR FUNDING PRE-CLINICAL
RESEARCH.
WE HAVE MULTIPLE WAYS FOR
FUNDING MANUFACTURE AND
TRANSLATIONAL RESEARCH, AND WE
HAVE SOME CLINICAL TRIALS
NETWORKS THAT ARE EITHER FUNDED
BY US OR AFFILIATED TO DO
CLINICAL TRIALS.
WE ONLY HAVE ONE MECHANISM, AND
THAT'S CHAVD, THAT ALLOWS AN
INVESTIGATOR TO GO FROM AN IDEA
ALL THE WAY THROUGH THE
DEVELOPMENT OF THAT IDEA
PRECLINICALLY INTO GMP
MANUFACTURE TO DELIVER PRODUCTS
TO THE HVTN FOR CLINICAL TRIALS.
AND THAT IS CHAVD.
SO THE ROLE OF THE CHAVI
ITERATIONS IN HIV VACCINE
DEVELOPMENT IS PROFOUND.
BEFORE WAS THE EMPIRICAL
APPROACH, THEY WOULD FORMULATE A
VACCINE BASED ON A REASONABLE
HYPOTHESIS, THEN CONDUCT PHASE
ONE, PHASE TWO AND PHASE THREE
CLINICAL TRIALS, LOOKING FOR AN
EFFICACY SIGNAL IN PHASE 2B OR
PHASE 3.
THEY WOULD THEN PERFORM IMMUNE
CORRELATES OF PROTECTION
ANALYSIS USING SAMPLES FROM THAT
EFFICACY STUDY AND THEN REDESIGN
THE VACCINE TO ENHANCE THE
CORRELATIVE IMMUNE RESPONSES AND
THEN GO BACK TO THE START OF
CLINICAL DEVELOPMENT WITH PHASE
1, THEN PHASE 2, THEN PHASE
3 CLINICAL TRIALS LOOKING FOR AN
INCREASED EFFICACY SIGNAL IN
PHASE 3.
THE DIVISION OF AIDS WITH THE
COLLABORATION OF OTHERS HAS
FUNDED SEVEN LARGE SCALE
EFFICACY STUDIES FOLLOWING THIS
APPROACH.
ONLY ONE SHOWED MINIMAL EFFIC
EFFICACY, AND THE FOLLOW-UP
TRIAL TO THAT BASED ON THE
ANALYSIS, CORRELATES ANALYSIS OF
EFFICACY TRIAL SAMPLES FAILED TO
SHOW ANY EFFICACY AT ALL.
SO IN 2003, LEADING HIV VACCINE
INVESTIGATORS GOT TOGETHER AND
PUT TOGETHER AN ARTICLE IN
SCIENCE MAGAZINE THAT CALLED FOR
A NEW APPROACH TO HIV VACCINE
DEVELOPMENT.
THEY CALLED FOR A NEW WAY OF
THINKING ABOUT PROBLEMS,
BASICALLY WHAT THEY WERE CALLING
FOR WAS LARGE SCALE
COLLABORATIONS TO BREAK THROUGH
THE BARRIER OF OUR UNDERSTANDING
TO MAKE AN HIV VACCINE.
THE DIVISION OF AIDS ROSE THO TO
THAT CHALLENGE BY FUNDING THE
CENTER FOR HIV/AIDS VACCINE
IMMUNOLOGY OR CHA VEE.
THICHAVI.THIS WAS FUNDED -- WITY
LARGE BUDGET, $15 MILLION IN THE
FIRST YEAR, RISING TO ABOUT
$48 MILLION A YEAR FOR THE
SUBSEQUENT SIX YEARS.
PLEASE NOTE THAT THE GOAL WAS
NOT TO MAKE THE HIV VACCINE.
THE GOAL WAS TO INVESTIGATE THE
ROAD BLOCKS TO HIV VACCINE
DEVELOPMENT AS IN WHY THE
INITIAL IMMUNE RESPONSE OF
PEOPLE INFECTED WITH HIV FAILED
TO CONTROL AND ELIMINATE THE
VIRUS.
CHAVI WAS IN IK CYST TENSE FOR
SEVEN YEARS AND MADE MULTIPLE
DISCOVERIES THAT LED TO WHAT IS
NOW THE PATH THAT HIV VA VACCINE
DEVELOPMENT IS TAKING.
FIRST OF ALL THEY ENROLLED A
COHORT OF ABOUT 300 INDIVIDUALS
WHO HAD BEEN ACUTELY INFECTED.
THEY FOLLOWED THOSE INDIVIDUALS
FOR TWO TO FIVE YEARS, AND THIS
WAS BEFORE THE RECOMMENDATION
WAS FOR PEOPLE TO BE PUT ON
TREATMENT AS SOON AS THEY WERE
DIAGNOSED.
THEN THE RECOMMENDATION WAS FOR
PEOPLE TO ONLY BE PUT ON
TREATMENT WHEN THEIR CD4 COUNT
DROPPED TO A CERTAIN LEVEL, SO
MANY OF THESE PEOPLE WERE
FOLLOWED FOR TWO TO FIVE YEARS
WITH FREQUENT BLOOD DRAWS SO
INVESTIGATORS COULD LOOK AT WHAT
WERE THE IMMUNE RESPONSES AND
HOW WAS THE VIRUS EVOLVING IN
RESPONSE TO THOSE IMMUNE
RESPONSES.
THIS TRIAL COULD NOT BE REPEATED
TODAY BECAUSE THAT WOULD BE
UNETHICAL.
WHAT CHAVI DISCOVERED WAS THAT
EARLY IMMUNE RESPONSES PARTIALLY
BUT DO NOT FULLY CONTROL THE
VIRUS.
EARLY CD8 POSITIVE T-CELL
RESPONSES DID REDUCE INITIAL
VIREMIA, BUT ESCAPED VARIANTS
EASILY AND QUICKLY AROSE.
EARLY NEUTRALIZING ANTIBODY
RESPONSES WERE NARROWLY TYPE
SPECIFIC AND ESCAPED FROM EASILY
ALSO.
HOWEVER, LATER INFECTION, AFTER
TWO TO THREE YEARS, MANY PEOPLE,
10 TO 20% OF PEOPLE, DEVELOPED
BROADLY NEUTRALIZING ANTIBODIES.
THESE COULD BE ISOLATED FROM
THEIR BLOODSTREAM AS MONOCLONAL
ANTIBODY, AND THOSE MONOCLONAL
ANTIBODIES WERE STUDIES AND IT
WAS REALIZED THAT THEY WERE NOT
IN THE GERMLINE, THEY WERE THE
RESULT OF SIGNIFICANT AMOUNT OF
SOMATIC HYPERMUTATION OR
EVOLUTION OF THE ANTIBODIES IN
RESPONSE TO THE EVOLUTION OF THE
VIRUS.
THIS WAS A BREAKTHROUGH IN OUR
UNDERSTANDING.
FROM THIS, THE B CELL
LINEAGE-BASED HYPOTHESIS WAS
DEVELOPED.
SO THE NEW UNDERSTANDING, AND
THIS WAS BASED ON PRIOR RESEARCH
DONE AT THE VRC, WHERE THEY HAD
OBSERVED THE PASSIVE TRANSFER OF
NEUTRALIZING ANTIBODIES INTO
NON-HUMAN PRIMATES, WOULD
PROTECT THOSE NON-HUMAN PRIMATES
FROM MUCOSAL INFECTION BY SHIV,
O.HOWEVER, WHAT CHAVI SHOWED WAS
THAT ANTIHIV BROADLY
NEUTRALIZING ANTIBODIES ARE NOT
ENCODED IN THE GERMLINE.
SO HOW ARE THEY TO BE INDUCED?
WELL, RARE BNAB PRECURSOR B
CELLS MUST BE ENGAGED AND
UNDERGO SOMATIC HYPERMUTATION IN
THEIR ANTIBODY GENES TO EVOLVE
INTO ANTIHIV BNABs.
HIV VACCINE DESIGN THUS
REQUIRES, ONE, IDENTIFICATION OF
THE RARE BNAB PRECURSORS THAT
CAN EVOLVE INTO BNABs, TWO,
DESIGN OF IMMUNOGEN CONSTRUCTS
THAT CAN ENGAGE BNAB PRECURSOR,
AND THREE, DESIGN OF BOOSTING
IMMUNOGENS THAT CAN GUIDE
SOMATIC HYPERMUTATION FORMAT
RANGE OF MOTION OF THOSE INITIAL
NARROWLY TYPE SPECIFIC
ANTIBODIES INTO BNABs.
DR. FAUCI RECOGNIZED THIS AS A
PARADIGM SHIFT IN THINKING ABOUT
HIV VACCINE DEVELOPMENT AND
LABELED IT THE THEORETICAL
APPROACH.
SO AS CHAVI WAS COMING TO AN
END, WE HAD TO DECIDE WHAT TO
DO, AND WE GOT ADVICE FROM THE
AVRS, OUR AIDS VACCINE RESEARCH
SUBCOMMITTEE, THAT NOW WAS THE
TIME, OR THEN WAS THE TIME, TO
FUND A LARGE SCALE INITIATIVE IN
DEVELOPMENT OF THOSE IMMUNOGENS
THAT COULD INDUCE BNABs.
AND SO WE DID THAT WITH THE
CENTER FOR HIV/AIDS VACCINE
IMMUNOLOGY AND I MU GENERAL IMMN
DISCOVERY, OR CHAVI-ID, AND THE
GOAL WAS TO DEVELOP IMMUNOGENS,
A U19 MECHANISM FOR SEVEN YEARS
WITH A $31.5 MILLION SETASIDE TO
FUND ONE TO TWO AWARDS.
TWO AWARDS WERE FUNDED IN 2012,
AND THEY WERE EXTREMELY
PRODUCTIVE BETWEEN 2012 AND
2019.
THEY DEFINED THE FIVE ENVELOPE
PROTEIN TARGET SITES FOR BNAB
INDUCTION.
THEY DEFINED MORE BNAB LINEAGES.
THEY DEFINED THE STRUCTURAL
SHORTCUT OR REDUCTIONIST
APPROACH TO BNAB INDUCTION TO
COMPLEMENT LIN YANK HJ BASED
DESIGN.
AND MANY IMMUNOGENS WERE
DESIGNED AND ANIMAL-TESTED TO
ENGAGE KNOWN GERMLINE BNAB
PRECURSORS, AND THE FIRST
CLINICAL TRIAL TO RECRUIT RARE
GERMLINE BNAB PRECURSORS IN
HUMANS WAS SUCCESSFUL.
SO AS THAT WAS COMING TO AN END,
WE HAD TO DECIDE WHAT TO FOLLOW
THAT UP WITH.
WE DECIDED TO FOLLOW THAT UP
WITH MORE SEVEN-YEAR BIG SCIENCE
AWARDS TO ACTUALLY GET THE
INVESTIGATORS TO DESIGN MORE
IMMUNOGENS AND MANUFACTURE THEM
AND GET THEM INTO CLINICAL
TRIALS.
ONCE AGAIN, THERE WAS A SETASIDE
FOR $34.5 MILLION TO FUND ONE TO
TWO AWARDS.
AND TWO AWARDS WERE FUNDED.
AND THOSE ARE TO BE IN EXISTENCE
FROM 2019 UNTIL 2026, WHICH IS
TWO MORE YEARS IN THE FUTURE.
HOWEVER, THEY HAVE BEEN
INCREDIBLY PRODUCTIVE, EVEN WITH
THE PROBLEM OF HAVING TO STOP
AND SUS SPENT RESEARCH PARTIALLY
DURING THE COVID PANDEMIC.
THEY HAVE DEVELOPED IMMUNOGENS
THAT HAVE GONE INTO 11
EXPERIMENTAL PHASE ONE CLINICAL
TRIALS THROUGH THE VTN.
THEY HAVE MANUFACTURED NINE
DESIGN PRIMING IMMUNOGENS AND
NINE BOOSTING IMMUNOGENS FOR VTN
TRIALS.
THEY HAVE ADDED THE MRNA-LIPID
NANOPARTICLE PLATFORM TO
ACCELERATE AND IMPROVE IMMUNOGEN
DESIGN AND EVALUATION.
THEY HAVE DEVELOPED MULTIPLE
KNOCK-IN MOUSE MODELS FOR
TESTING BNAB INDUCING
IMMUNOGENS, AND THESE ARE NOT
JUST BEING USED BY THESE TWO
GROUPS, BUT THEY'RE ALSO BEING
USED BY HIV VACCINE DEVELOPERS
AROUND THE COUNTRY AND AROUND
THE WORLD INDEED.
THEY HAVE DESIGNED PRIMING AND
BOOSTING IMMUNOGENS TO ENGAGE
4 OF THE 5 BNAB TARGET SITES,
AND THEY'VE ALSO DEVELOPED THE
SLOW AND/OR FRACTIONATED DOSING
REGIMENS THAT HAVE BEEN SHOWN TO
PROMOTE GERMINAL CENTER
DEVELOPMENT AND SOMATIC
HYPERMUTATION IN ANIMALS, AND
THOSE REGIMENS HAVE GOTTEN IN TO
HVTN CLINICAL TRIALS.
SO WHAT WE WERE PROPOSING FOR
THE SCOPE OF THIS NEW
INITIATIVE, CHAVDI, THESE ARE
THE TWO MOST IMPORTANT POINTS OF
THE SCOPE.
FIRST OF ALL, WE WANT THEM TO
DESIGN THE RULES FOR PRIME AND
BOOST IMMUNOGEN DESIGN.
THIS HAS TO BE TURNED INTO A
SCIENCE.
RIGHT NOW THEY'RE JUST
CONSTRUCTING MULTIPLE CONSTRUCTS
FOR EACH BNAB TARGET.
THEY'RE TAKING THEM THROUGH
MULTIPLE ROUNDS OF TESTING IN
MOUSE MODELS, IN NON-HUMAN
PRIMATES BEFORE THEY GET THEM
INTO HUMANS.
THIS IS EXTREMELY LABORIOUS.
THIS IS NOT SOMETHING THAT
INDUSTRY WILL EVER TAKE OVER.
SO WE WANT THEM TO WORK OUT THE
SCIENCE BEHIND THIS, TO
UNDERSTAND THE INTERPLAY BETWEEN
B CELL FREQUENCY, IMMUNOGENICITY
AND DOSE TO RATIONALLY SELECT
PRIMING AND BOOSTING IMMUNOGENS.
SO THAT OTHER PEOPLE CAN DO
THIS.
WE ALSO NEED THEM TO UNDERSTAND
THE DYNAMICS OF GERMINAL CENTER
MAINTENANCE AND BOOST TIMING,
AND THEN WE WANT THEM TO GO ON
FOR FROM UNDERSTANDING THE
SCIENCE TO ACTUAL DESIGN, GMP
MANUFACTURE AND GET INTO
CLINICAL TRIALS THE TESTING OF
MORE PRIMING AND BOOSTING
IMMUNOGENS TO UNDERSTAND HOW TO
GUIDE SOMATIC HYPERMUTATION OF
MULTIPLE BNAB LINEAGES AT THE
SAME TIME WITHOUT INTERFERENCE,
AND TO ACTUALLY DEMONSTRATE THAT
THEY CAN GET TO A REASONABLE
TITER OF BROADLY NEUTRALIZING
ANTIBODIES.
NEUTRALIZING ANTIBODIES THAT
WILL NEUTRALIZE AT LEAST 50% OF
THE GLOBAL -- HIV ISOLATES.
AND WE WANT THEM TO DO THAT IN
EITHER A RIGOROUS NON-HUMAN
PRIMATE MODEL OR IN PHASE ONE
CLINICAL TRIALS.
AND WE ALSO WANT THEM TO HARNESS
THE TECHNOLOGY TO COMBINE PRIMES
AND BOOSTS IN SIMPLIFIED OR
SINGLE SHOT REGIMENS.
WE KNOW THERE ARE PEOPLE THAT
ARE WORKING ON THESE
TECHNOLOGIES.
BUT WE WANT TO EXPAND THE SCOPE
A LITTLE BIT MORE.
WE WANT THEM TO EXPAND THE SCOPE
TO WORK ON THERAPEUTIC HIV
VACCINE RESEARCH.
WE USE SOME OF THE SAME PRODUCTS
THAT THEY ARE DESIGNING FOR
PREVENTIVE VACCINES, BUT WE WANT
THEM TO WORK WITH THE
THERAPEUTIC VACCINE PEOPLE TO
GET THESE INTO TESTING IN PEOPLE
WHO ARE LIVING WITH HIV.
BECAUSE WE WANT TO SEE HOW THESE
PERFORM IN PEOPLE WHO HAVE
ALREADY BEEN PRIMED TO HIV
ANTIGENS.
THIS IS THE HARDEST CASE
SCENARIO.
AND WE CAN CONTRIBUTE -- OUR
INVESTIGATORS IN CHAVDI CAN
CONTRIBUTE TO THE THERAPEUTIC
VACCINE PEOPLE THEIR GMP
MANUFACTURING CAPABILITY, BUT WT
THEY, BUTTHEY CAN GET AN EARLY N
HOW WELL THESE PRODUCTS DO IN
PEOPLE AND AN EARLY READ ON
WHETHER OR NOT THE IMMUNE
RESPONSES THAT THESE PRODUCTS
WILL INDUCE WILL ACTUALLY IMPACT
THE COURSE OF INFECTION.
WE ALSO WANT THEN TO BE ABLE TO
WORK ON OTHER COOPERATING IMMUNE
RESPONSES, PROOF THAT OTHER
IMMUNE RESPONSES WILL COOPERATE
WITH BNABs, TO ALLOW LOWER
TITERS TO BE PROTECTED, BUT NOT
JUST PROOF OF THAT IN A
NON-HUMAN PRIMATE CHALLENGE
MODEL BUT WE WANT THEM TO DIG
MORE DEEPLY INTO THAT TO
DETERMINE THE MECHANISTIC
CORRELATE OF THIS COOPERATION.
SO THAT WE KNOW WHAT TO MEASURE
IN PHASE ONE CLINICAL STUDIES,
AND WHAT TO OPTIMIZE IN PHASE
TWO STUDIES BEFORE EFFICACY
STUDIES TO AVOID RETURNING TO
RISKY EMPIRICAL VACCINE
DEVELOPMENT.
WHAT WILL NOT BE ALLOWED IS
APPLICATIONS JUST FOCUSED ON
THERAPEUTIC HIV VACCINE RESEARCH
OR ON APPLICATIONS JUST FOCUSED
ON T-CELL OR OTHER COOPERATING
IMMUNE RESPONSES.
SO WE HAD THIS PRE-REVIEWED BY
TWO ARAC MEMBERS, DR. CYNTHIA
DERDEYN, WHO IS ON THE LINE, AND
DR. REUBEN HARRIS, WHO MAY JOIN
BUT HE'S AT A CONFERENCE IN
CHINA SO HE MAY NOT JOIN.
THE REVIEWERS WERE GENERALLY
SUPPORTIVE OF THE INITIATIVE,
AND WE THANK THEM FOR THEIR
CONSTRUCTIVE FEEDBACK.
ONE OF THE THINGS THAT WAS SAID
WAS THAT OVERALL CHAVDI SERVES
AS A FLAGSHIP WITH HIGH
VISIBILITY WITHIN THE PORTFOLIO
OF THE VACCINE RESEARCH PROGRAM
THAT IS CRITICAL FOR SUCCESS.
THERE IS AN UNEQUIVOCAL NEED FOR
THE SCIENCE THAT WILL BE
SUPPORTED BY THIS PROGRAM.
ALSO, AN IMPORTANT ASPECT OF
CHAVDI WILL BE THE FOCUS ON
TRANSLATABILITY OF THE
SUCCESSFUL VACCINE APPROACHES
INTO CLINICAL MANUFACTURING AND
TESTING.
BUT ON THE LESS POSITIVE SIDE,
THEY SAID THAT APPLICANTS SHOULD
PROVIDE CLEAR MILESTONES HALFWAY
AND FULL TERM MILESTONES, AND
THEY SHOULD BE HELD ACCOUNTABLE.
WELL, THIS IS NATURAL TO ASSUME
BECAUSE WE'RE GIVING THEM SO
MUCH MONEY, AND WE EXPECT MORE
ACCOUNTABILITY FROM
INVESTIGATORS THAT ARE WORKING
WITH A LARGE CHUNK OF MONEY THAN
WE EXPECT FROM INVESTIGATORS
WORKING WITH SMALLER CHUNKS OF
MONEY.
SO WE WILL INSTITUTE A CRITICAL
REVIEW AT THE END OF THE THIRD
YEAR OF THE FIVE YEARS, AND THE
LEVEL OF FUNDING IN YEARS FOUR
AND FIVE WILL DEPEND ON THE
SUCCESS OF THAT REVIEW.
ANOTHER COMMENT WAS MADE, SINCE
THE GOAL IS DURABLE PROTECTION
OF UNINFECTED PEOPLE FROM NEW
HIV INFECTIONS, THE MECHANISM
SHOULD ALLOW FOR OTHER
INNOVATIVE AFFINITY-BASED
APPROACHES TO PREVENT INFORECAST
SHUCH AS NANOPARTICLES.
WELL, WE THOUGHT ABOUT THIS.
WE ARE SUPPORTING THE
DEVELOPMENT OF THOSE SUCH
PRODUCTS THROUGH OTHER
MECHANISMS.
AND WE THINK THAT THE JOB OF
CHAVD TO DEVELOP THE SCIENCE OF
BE NAB INDUCTION IS IMPORTANT
ENOUGH AND IS GOING TO BE ENOUGH
WORK THAT WE DON'T WANT THEM TO
BE DISTRACTED BY STUFF THAT
WE'RE FUNDING WITH OTHER
INITIATIVES.
SO I RETURN TO THE INITIAL
INITIATIVE SLIDE, THE CONSORTIUM
FOR HIV VACCINE DEVELOPMENT AND
IMMUNOLOGY, AND I'VE LAID OUT
WHAT THE OBJECTIVE IS.
IT'S GOING TO BE A COOPERATIVE
AGREEMENT, FIVE-YEAR AWARDS WITH
$33 MILLION SETASIDE FOR TWO TO
THREE AWARDS.
SO THANK YOU FOR LISTEN NG.
ING.
I'I'LL TAKE QUESTIONS.
>> WHO WOULD LIKE TO START WITH
QUESTIONS?
ANYONE IN THE ROOM?
RM I DOI DON'T SEE ANYONE ONLIN.
CINDY, GO AHEAD.
>> YES.
THANKS SO MUCH, STUART.
THAT WAS A NICE PRESENTATION.
I JUST SORT OF WANTED TO
REITERATE THAT I THINK THERE
SHOULD BE SOME LIMITS ON
REPEATING THINGS THAT HAVE
ALREADY BEEN DONE, YOU KNOW,
THINGS LIKE BNAB KNOCK-IN MICE,
THAT'S BEEN DONE SORT OF
EXHAUSTIVELY.
I THINK PROPOSING THAT IN THIS
NEW INITIATIVE WOULD NOT BE A
MAJOR ADVANCEMENT, AND I THINK,
YOU KNOW, FINDING NEW BNABs
AND WE HAVE SO MANY NOW, SO I
THINK HAVING SOME LIMITATION OR
ENCOURAGING SOMEWHERE IN THE
ANNOUNCEMENT THAT WE'RE NOT JUST
GOING TO REPEAT THE THINGS THAT
HAVE BEEN DONE BUT REALLY GOING
TO ADVANCE AND BUILD ON WHAT'S
BEEN DONE, YOU KNOW, IN THE --
PROBABLY MOSTLY IN THE LAST --
BUT IN THE FIELD GOING FORWARD.
BECAUSE I THINK SOME OF THOSE
ARE -- THEY'RE EASY TO DO BUT
THEY'RE NOT GOING TO ADVANCE TO
WHERE I THINK THAT YOU WANT THIS
TO GO.
>> SO I COMPLETELY AGREE WITH
YOU, AND IF YOU WILL HAVE
NOTICED -- YOU WILL HAVE NOTICED
FROM THE SUBSEQUENT -- FROM EACH
ITERATION AND EACH ITERATION
INITIATIVE SLIDE, WE'RE ASKING
THEM TO DO MORE, BECAUSE THEIR
MISSION EVOLVES AS THE SCIENCE
HAS EVOLVED.
WE DON'T WANT THEM TO GO BACK TO
MAKING MORE KNOCK-IN MOUSE
MODELS OR ISOLATING MORE BROADLY
NEUTRALIZING MONOCLONAL
ANTIBODIES.
THEY CERTAINLY HAVE ENOUGH OF
THOSE.
WE WANT THEM TO FOCUS IN THIS
NEXT ITERATION ON THE GMP
MANUFACTURING OF PRODUCTS THAT
WILL BE DLIMPED DELIVERED TO THN
BECAUSE WE WANT THEM TO PROVE
THE CONCEPT IN PHASE ONE
CLINICAL TRIALS THAT THEY CAN
INDUCE BNABs.
AND WE WANT THEM TO WORK OUT THE
SCIENCE BECAUSE THEY WILL HAVE
TESTED SO MANY DIFFERENT
PRODUCTS, THEY SHOULD BE ABLE TO
ACCUMULATE ENOUGH DATA WITH THE
VTN LABS TO WORK OUT THE SCIENCE
BEHIND THE DESIGN OF NEW PRIMING
AND BOOSTING IMMUNOGENS.
THE NIAID, THE DIVISION OF AIDS,
WE DID NOT ESSENTIALLY FUND
PRODUCT DEVELOPMENT.
WE FUND THE DEVELOPMENT OF THE
SCIENCE THAT ENABLES PRODUCT
DEVELOPMENT.
>> ARE THERE OTHER QUESTIONS?
OKAY.
THANK YOU FOR THAT.
PLEASE, EVERYBODY, PUT IN YOUR
VOTE.
MARTINA, DO YOU WANT TO -- I
THINK YOU'RE NEXT.
MARINA, YOU WANT TO COME UP?
>> GOOD AFTERNOON.
>> WE CAN'T HEAR YOU VERY WELL.
MOVE THE MIC.
>> HELLO?
NO?
OH.
GOOD AFTERNOON.
MY NAME IS MARINA PROTOPOPOVA.
I AM A PROGRAM OFFICER AND HERE
TO PRESENT THE CONCEPT FOR A NEW
INITIATIVE, ADVANCING
TRANSLATION OF LONG-ACTING
STRATEGIES FOR HIV AND
HIV-ASSOCIATED COINFORECASTS.
IN SHORT, AT LAST.
THIS CONCEPT WAS DEVELOPED BY
TWO PROGRAMS, THERAPEUTICS
RESEARCH PROGRAM AND PREVENTION
SCIENCES PROGRAM, AND I'M HERE
ON BEHALF OF A GROUP PROGRAM
OFFICERS WHO ARE WORKING TO
DEVELOP THIS INITIATIVE.
THE MAIN OBJECTIVE OF OUR NEW
INITIATIVE IS PRODUCT
DEVELOPMENT.
WE ACTUALLY -- OBJECTIVE IS TO
BUT SORT PRE-CLINICAL ACTIVITIES
FOR DEVELOPMENT OF SAFE AND
EFFECTIVE LONG-ACTING/SUSTAINED
RELEASE TECHNOLOGIES FOR
PREVENTION AND TREATMENT OF HIV
AND HIV-ASSOCIATED COINFECTIONS,
AND TO ULTIMATELY PROVIDE
INFORMATION AND PROVIDE THE DATA
TO BE INCLUDED INTO SUBMISSION
OF IND APPLICATION TO THE FDA.
SO THE MAIN OVERALL GOAL IS
WE'RE AIMING TO FACILITATE THE
TRANSLATION OF INNOVATIVE
TECHNOLOGIES,
LONG-ACTING/SUSTAINED RELEASE,
FROM R & D TO IND.
THIS IS NEW, IT'S RFA GRANT,
ACTIVITY CODE IT'S R61/R33, NO
CLINICAL TRIALS, DURATION OF
AWARD FIVE YEARS, TWO YEARS FOR
THE FIRST PHASE, THREE YEARS FOR
THE SECOND.
FIRST TOTAL COST FOR INITIATIVE
$4 MILLION, EXPECTING TO FUND
THREE TO FOUR APPLICATIONS.
AGAIN, PARTNERS, WE ARE PARTNERS
ON DEVELOPING THE LONG-ACTING
SUSTAINED RELEASE THERAPEUTICS,
THERAPEUTICS RESEARCH PROGRAM
AND PREVENTION SCIENCES PROGRAM.
THIS INITIATIVE WILL ADDRESS THE
PRIORITIES OF O.A.R., OFFICE FOR
AIDS RESEARCH, DEVELOP NEXT
GENERATION EFFECTIVE TREATMENTS,
REDUCE HIV INCIDENCE AND HALT
THE SPREAD OF HIV INFECTION BY
DEFINING HIGHLY EFFECTIVE
PREVENTION STRATEGIES, AND
ADDRESS HIV COMORBIDITIES AND,
INFECTIONS AND COMPLICATIONS.
THIS IS A RAPIDLY DEVELOPING
FIELD, AND BECAUSE DEVELOPMENT
OF -- BECAUSE SAFE, EFFECTIVE
AND ACCEPTABLE STRATEGIES WILL
SIMPLIFY DOSING REQUIREMENTS AND
POTENTIALLY LEAD TO IMPROVED
ADHERENCE AND REDUCE EMERGENCE
OF DRUG RESISTANCE.
BECAUSE IN HIV, WE LOOK AT THAT
HERE AND STILL VARIES BETWEEN
27% TO 80 ACROSS DIFFERENT
POPULATIONS IN VARIOUS STUDIES.
IN HIV AND TB, WE'RE LOOKING AT
THE LONG -- UP TO 24 MONTHS
TREATMENT REGIMEN FOR
TUBERCULOSIS, ADHERENCE IS
CRITICAL, ESPECIALLY FOR DRUG
RESISTANT -- IN HBV WITH
LONG-ACTING ANTIRETROVIRALS
MOVING IN THE CLINIC, THE
COMPATIBLE -- DEVELOPMENT OF
COMPATIBLE LO LONG-ACTING
TREATMENTS FOR HBV WILL BE
REQUIRED, AND GLOBALLY, WE'RE
LOOKING AT HIV AND HCV, AND THIS
WOULD BE A VERY IMPORTANT
SOLUTION TO THE PROBLEM IF WE
CAN DETECT AND TREAT THE HCV,
AND THIS IS WHY THE DEVELOPMENT
OF LONG-ACTING FORMULATION TO BE
USED AS A SINGLE DOSE
ALTERNATIVE WILL HELP EY ELIMINE
HCV.
UNDERSTANDING THE CRITICAL NEED
AND PROMISE POTENTIAL AND THE
CHALLENGES, THE DIVISION HAD
SEVERAL INITIATIVES AND IT HAS
PUT ENORMOUS RESOURCES TO
DEVELOP THIS FIELD FORWARD, TO
MOVE THIS FIELD FORWARD AND
DEVELOP PROMISING TECHNOLOGIES.
OUIN BOTH PROGRAMS -- HAS VERY
PROMISING INTERESTING
TECHNOLOGIES THAT ALREADY SHOWED
HIGH POTENTIAL.
SO WE HAVE TWO TECHNOLOGIES ALL
RIGHT ALREADY IN CLINICAL TRIALS
AND THEY WERE DEVELOPED WITH OUR
FUNDING.
WE HAVE THE TECHNOLOGY IN --
THEY JUST MARK DIFFERENT COLORS
SO WE'RE LOOKING AT THE
TECHNOLOGIES ARE IN BLUE.
THEY ARE ENTER IND DEVELOPMENT
OR JUST ABOUT TO ENTER, AND IN
GREEN, THIS IS JUST EXAMPLES OF
THE TECHNOLOGY THAT ARE OUT
THERE THAT THEY ALREADY HAVE
POTENTIAL TO TREAT OR PREVENT
HIV AND GETTING NOW EVEN TB AND
HPV, THAT THHBV, PROBABLY IN A ,
THEY WILL BE ENTERING THE
PRE-IND DEVELOPMENT STUDIES.
WITH THAT, WHILE WE CELEBRATE
THE SUCCESSES OF OUR FUNDING AND
OUR INVESTIGATORS, WE ALSO
UNDERSTAND THAT THERE IS -- THEY
ARE GETTING INTO THE SO-CALLED
VALLEY OF DEATH IN DRUG
DEVELOPMENT, WHERE ACTUALLY
GETTING THROUGH -- THROUGH IND
DEVELOPMENT, IND DIRECT
PRE-CLINICAL STUDIES, FILING IND
IN EARLY PHASE ONE AND CLINICAL
TRIALS, WILL REQUIRE FUNDING
PARTNERSHIPS, EXPERTISE, SO FOR
US AS A FUNDING AGENCY, IT'S
VERY IMPORTANT TO HELP
INVESTIGATE, TO AID
INVESTIGATORS TO SUCCEED GOING
THROUGH THE VALLEY OF DEATH AND
FOR US IS VERY IMPORTANT TO
ADVANCE PROMISE IN TECHNOLOGY
TOWARDS CLINICAL TRIALS.
SO IT'S CRITICAL, IDENTIFY GAPS,
REMOVE THE ROADBLOCKS AND
PROVIDE TIMELY FUNDING TO
SUPPORT THE RESOURCES.
AND WE BELIEVE THAT OUR PROPOSED
NEW CONCEPT, NEW INITIATIVE,
WILL FILL THIS GAP, THAT WILL
PROVIDE THE FUNDING TO ENABLE
PRE-CLINICAL PRODUCT
DEVELOPMENT, PRE-IND STUDIES,
IND-DIRECTED PRE-CLINICAL
DEVELOPMENT.
THE SCOPE.
SCOPE OF THIS INITIATIVE IS --
LOOKING AT THE FUNDING
PRE-CLINICAL RESEARCH TO MEET
PRE-CLINICAL RESEARCH
REQUIREMENTS, SO WE'RE LOOKING
AT MOSTLY THE TWO SECTIONS OF
IND.
SO IT'S ANIMAL TOX PHARMACOLOGY
AND THE CHEMISTRY MANUFACTURING
AND CONTROL.
SO THE SCOPE MAY INCLUDE BUT NOT
LIMITED TO IND-DIRECTED
PHARMACOLOGY AND TOXICOLOGY
STUDIES TO ADDRESS REGULATORY
REQUIREMENTS FOR CLINICAL
SAFETY, TOXICOLOGY AND DRUG
DOSING PARAMETERS.
SPECIALIZED TOXICITY TET
TESTING.
ADVANCED IN VIVO EFFICACY
STUDIES IN APPROPRIATE MODELS TO
CONFIRM OR ESTABLISH EFFICACIOUS
DOSE, WHICH WILL BE VERY
IMPORTANT HERE, ES PESH LI ESPEN
LIEU OF CONDUCTING THE
TOXICOLOGY STUDIES AND
DETERMINING WHAT IS THE SAFE
DOSE.
PROCESS DEVELOPMENT AND
ANALYTICAL DEVELOPMENT SCALEUP
PRODUCTION, GMP MANUFACTURING,
STABILITY TESTING BASED ON FDA
GUIDANCE, REGULATORY ACTIVITY,
INCLUDING PREIND MEETINGS, AND
WE ALSO PURPOSELY INCLUDED -- WE
SAW IT WAS VERY IMPORTANT TO
INCLUDE HERE, NON-CLINICAL
STUDIES OF CLINICAL STAGE
PRODUCTS, BECAUSE GETTING FROM
PHASE ONE TO PHASE TWO AND
FURTHER WILL REQUIRE SPECIALIZED
TOXICOLOGY TOXICITY TESTING,
CARCINOGENICITY.
SO OUT OF SCOPE, IT WILL BE
CLINICAL TRIALS AND EARLY
DEVELOPMENTAL WORK, AND WE WILL
REFER INVESTIGATORS TO A
DIFFERENT INITIATIVE THAT WE
HAVE ONGOING IN THE DIVISION.
ELIGIBILITY.
BESIDES SMALL BUSINESSES, IT
WILL OPEN -- THE ACADEMIC
INVESTIGATORS WILL BE ELIGIBLE
TO APPLY, FOREIGN INSTITUTIONS,
AS PART OF THE DEVELOPMENT.
BUT THERE ARE REQUIREMENTS.
THE REQUIREMENTS WE WILL BE
LOOKING AT MATURE ENOUGH
TECHNOLOGY THAT ALREADY
DEMONSTRATED THERAPEUTIC EFFECT
AND APPROPRIATE ANIMAL MODELS
AND INTERMITTENT DOSING FROM
EITHER SINGLE ADMINISTRATION OR
CONTINUOUS DOSING.
AND IN THE HIV COMMUNITY IT'S
GOING TO BE A MINIMUM OF ONE ONE
EVERY THREE MONTHS DOSING AND
TB, HBV OR HCV, A MINIMUM OF
ONCE A MONTH DOSING.
SO PROPOSED STRATEGY HAS
DEMONSTRATED COMPETITIVE
ADVANTAGE.
WHAT WE'RE TALKING ABOUT, WE'RE
TALKING ABOUT THE DURATION OF
THOSE IN IMPROVEMENT OF VOLUMES,
VISIBILITY OF SCALE TORE
COST-EFFECTIVENESS, THE -- TO
NAME JUST AS EXAMPLES.
RESEARCH PLAN MUST INCLUDE
TARGET PRODUCT PROFILE AND
ADDRESS ALL IND COMPONENTS,
WHILE WE SAY IT WILL FUND A
MAJORITY OF THE PRE-CLINICAL
RESEARCH, IT'S TWO SECTIONS,
HOWEVER, UNDERSTANDING THE WHOLE
PROGRAM WOULD BE VERY IMPORTANT
TO ACTUALLY -- TO FORMULATE WHAT
STUDIES WILL BE NEEDED.
MILESTONES AND GO/NO-GO
DECISIONS WITH THE TIMELINE ARE
VERY -- WILL BE REQUIRED.
AND ADDRESS IPIS P ISSUES TO ENE
FREEDOM TO OPERATE AND DATA
SHARING, AND THE PRODUCT
DEVELOPMENT ITSELF REQUIRES
MULTIDISCIPLINARY EXPERTISE.
SO IT REQUIRES PEOPLE FROM
COMING TOGETHER IN PARTNERSHIP
BE COLLABORATIONS.
SO WE UNDERSTAND THAT
PARTICIPATION OF CROs ONE WAY
OR ANOTHER WILL BE -- WE
ANTICIPATE IT WILL BE NEEDED, SO
WE WILL REQUIRE INDUSTRY OR
TRANSLATIONAL PARTNER OR ADVI
ADVISOR.
WE ACTUALLY KNOW THIS BECAUSE OF
TRANSLATIONAL RESEARCH.
ALSO PART OF THE REQUIREMENT
WILL BE EXPERT ADVISORY BOARD OF
INDEPENDENT EXPERTS IN RELEVANT
AREAS FORMED SOON AFTERWARDS TO
GUIDE AND HELP THE INVESTIGATOR
AND THE TEAM IN THE ACTIVITIES.
MECHANISM.
IT WILL USE BIPHASIC R61/R33.
FIRST PHASE IS FOR TWO YEARS TO
OBTAIN CRITICAL RESEARCH TO
FURTHER DEMONSTRATE THE
FEASIBILITY AND COMPETITIVE
ADVANTAGE, AND R33 PHRASE WILL
ENABLE PRE-CLINICAL DEVELOPMENT
BEFORE IND SUBMISSION.
SO MILESTONES WILL BE REQUIRED
FOR BOTH PHASES, AND TO
FACILITATE CLINICAL TRANSLATION,
WE WILL REQUIRE A PLAN FOR
PRE-IND MEETING AND SUBMITTING
PRE-IND PACKAGE TO THE FDA.
TRANSITION MILESTONES FROM ONE
PHASE TO ANOTHER IS ALSO
CRITICAL HERE, BECAUSE THEY WILL
DEFINE SUCCESS DURING THE FIRST
PHASE AND CONSIDERATION FOR
FURTHER FUNDING AND WILL BE
NEGOTIATED WITH NIH STAFF.
WITH THE TRANSITION OF HOW IT'S
GOING TO LOOK.
SO BEFORE THE END OF R61, THE
AWARDEES SUBMIT THE TRANSITION
PACKAGE TO SAY THIS IS THE
PROGRESS -- OUR PROGRESS O UNDER
THE GRANT AND DESCRIBE THE
ADVANCEMENT TOWARDS THOSE
NEGOTIATED MILESTONES.
AND THE DISCONTINUATION OF R33.
WE UNDERSTAND THAT WE'RE LOOKING
AT THE RESEARCH, AND IT'S KIND
OF -- IT CAN BE SOMEWHAT
CIRCUMSTANCES AND THOSE
MILESTONES MAY BE REVISED, NOT
LARGELY BUT SOME MODIFIED AND
WILL BE NEGOTIATED WITH THE NIH
TO DETERMINE ELIGIBILITY FOR THE
AWARD PRIOR TO R33 AWARD.
SO R33 FUNDING DECISION WILL BE
BASED ON SUCCESSFUL COMPLETION
OF TRANSITION MILESTONES,
DEMONSTRATE ITS STRONG POTENTIAL
FOR TRANSLATION TO CLINICAL
TRIALS, PROGRAMMATIC PRIORITIES
AND AVAILABILITY OF FUNDS.
SO AGAIN, WE WERE -- THIS SLIDE
DEMONSTRATES WHERE WE ARE IN
TERMS OF OUR INITIATIVE AND
RESOURCES, AND THIS PARTICULAR
NEW INITIATIVE AT LAST WILL FEEL
MUCH NOTICEABLE TO OVERCOME
TRANSLATIONAL GAP IN WHAT WE
CURRENTLY HAVE.
THE SO IT WILL ALSO -- IT'S VERY
COHESIVE WITH ALL THE
INITIATIVES AND RESOURCES THAT
WE CURRENTLY HAVE.
TO ADVANCE INNOVATIVE TECHNOLOGY
AND TO IND AND CLINICAL TRIALS.
SO IN ADDITION TO JUST GOING
THROUGH, SO -- IT'S R01, IT'S
HYPOTHESIS DRIVEN MECHANISM.
WE ALSO HAVE SUSTAINED RELEASE
TREATMENT OR PREVENTION, AND
THIS INITIATIVE HAD BEEN -- BEEN
REISSUED SEVERAL TIMES, MORE
THAN 10 YEARS, BEEN QUITE
SUCCESSFUL.
LAST YEAR WE PUT FORWARD AND
IT'S ALREADY SHOWN INTEREST IN A
PLANNING STRATEGY GRANT, SO WE
ACTUALLY CONNECT THE
PRE-CLINICAL PROGRAM WITH THE
CLINICAL TRIALS.
SO THE ACTUAL LAYOUT, THE
PRE-IND STRATEGY TO ALLOW -- SO
WE ARE MOVING FROM OUR -- TO THE
CLINICAL TRIALS WITH THIS
PLANNING STRATEGY.
I DIDN'T MENTION, BUT THE
SUSTAINED RELEASE TREATMENT FOR
STRAT-T, WE FOCUS ONLY ON
INNOVATIVE TECHNOLOGY.
THIS IS WHERE THE EARLY
DEVELOPMENT, THE WORK.
THE CLINICAL TRIAL, THE GLOBAL
CLINICAL NETWORKS A AND, AGAIN,
WILL ALLOW THE TRANSLATION FROM
R ARND D TO IND IN THE CLINICAL
TRIALS TO LABEL THIS.
AS SBIR OPPORTUNITIES ARE STILL
THERE BUT IT'S OPEN FOR SMALL
BUSINESSES.
WE ALSO HAVE RESOURCES, VERY
VALUABLE.
IT'S A -- PROGRAM IN EXISTENCE
FOR THE LAST 10 YEARS AND HELPED
TREMENDOUSLY TO MOVE THE FIELD
FORWARD.
IT'S A RESEARCH PROGRAM THAT
RECEIVES BROAD BASED SCIENTIFIC
SUPPORT TO INVESTIGATORS WHO ARE
WORKING IN THAT FIELD, AND IT'S
VERY SUCCESSFUL, MANY WORKSHOPS,
PUBLICATIONS THERE ARE FANTASTIC
ABILITIES, THE WEBSITE, ANY
INVESTIGATOR WORKING IN THE
FIELD CAN SEE, THEY CAN TRACK
THE PRE-CLINICAL, CLINICAL,
REGULATORY MITIGATIONS FOR THE
HIV AND THE HIV COINFECTION, IN
MODEL SERVICED, SO IT'S A GREAT
RESOURCE BUT LAST BUT NOT LEAST
IT'S THE CLINICAL CONTRACT
SERVICES PROGRAM, TO HELP FIELD
INVESTIGATORS, OUR CONTRACTORS
DOING THE SERVICES, AND THIS IS
VERY VALUABLE RESOURCE.
SO THE TWO REVIEWERS WERE -- OF
THIS CONCEPT, IT'S DR. KEITH
JEROME AND RICHARD D'AQUILA.
I WOULD LIKE TO TAKE THIS
OPPORTUNITY TO THANK THEM AGAIN
FOR THEIR FEEDBACK, QUESTIONS
AND DISCUSSIONS.
IT WAS A GREAT DISCUSSION WE HAD
AND THEIR FEEDBACK WAS VERY,
VERY IMPORTANT TO US, AND
ENCOURAGING.
BOTH REVIEWERS WERE
ENTHUSIASTICALLY SUPPORTIVE OF
THIS CONCEPT, AND COMMENTED THAT
THIS INITIATIVE WILL HAVE
SUBSTANTIAL IMPACT ON THE FIELD,
AND TECHNOLOGICALLY WITHIN
REACH, GIVEN THE CURRENT
PIPELINE.
IT ESSENTIAL CHALLENGE ACTUALLY
MOVING EARLY STAGE RESEARCH
THROUGH SO CALLED VALLEY OF
DEATH AND OUR PROGRAM, THE
INITIATIVE WILL ADDRESS THIS
NEED IN A POWERFUL WAY, AND
ALMOST SURELY LEAD TO NEW
VALUABLE THERAPEUTICS, WHICH IS
VERY ENCOURAGING, THANK YOU.
AND ALSO IT'S A PLUS THAT AT
LAST IS BEING DIRECTED TO
ACADEMIC INNOVATORS AND EARLY
STAGE COMMERCIAL ENTITIES,
PARTICULARLY REMOVING POTENTIAL
ROADBLOCK FOR SOME ACADEMIC
GROUPS.
AND WE HAVE SOME VERY EXCITING
DEVELOPMENTS AND VERY
INTERESTING TECHNOLOGY AND GREAT
PROMISE FROM ACADEMIC
INSTITUTIONS AS WELL, AND THE
FACT THAT THIS MECHANISM ALLOWS
SOME FLEXIBILITY IN NEGOTIATING
R33 MILESTONE TO ALLOW TO FOCUS
ON THE END GOALS.
SUGGESTION WAS MADE THAT TO
INCLUDE THE LINKS TO ALL OUR
PROGRAMS THAT THEY FUND
OPPORTUNITY AND RESOURCES TO
HELP IN EVENTUAL RFA, TO HELP
INVESTIGATORS TO LEARN ABOUT ALL
THAT IS AVAILABLE.
AND THIS IS THE -- OUR AT LAST
INITIATIVE, AND WE'LL BE HAPPY
TO ANSWER QUESTIONS.
THANK YOU.
>> THANK YOU VERY MUCH.
OKAY.
LET START ONLINE.
ANY QUESTIONS THERE?
HOW ABOUT IN THE ROOM?
WE'LL PROBABLY NEED SOME
AFTERNOON DRINKS BEFORE WE START
GETTING MORE QUESTIONS.
RAPHI, GO AHEAD.
>> THANKS.
JUST TWO QUICK QUESTIONS.
IS THE INTENT THAT THERE WOULD
BE ONE AWARD FOR THIS?
IT DOESN'T SAY ON THE SLIDE, AND
I APOLOGIZE IF I MISSED --
>> I APOLOGIZE.
WE ARE LOOKING AT THE POTENTIAL
OF UP TO FOUR AWARDS HERE.
I REMOVED BY MISTAKE.
I'M SO SORRY.
>> NO WORRIES.
AND THEN MY OTHER QUESTION WAS,
HAVE THERE BEEN BACK CHANNEL
DISCUSSIONS WITHIN THE INSTITUTE
ABOUT THE REGULATORY SUPPORT
THAT THE INSTITUTES ARE WILLING
TO PROVIDE TO SUCCESSFUL
GRANTEES OF THIS NEW MECHANISM?
BECAUSE IT JUST STRIKES ME THAT
THE COMPLEXITY OF NEW DRUG
DEVELOPMENT HAS ENORMOUS
REGULATORY COMPLICATIONS, AND DO
THE INSTITUTES HAVE EITHER
CONSULTANTS OR IS THERE IN-HOUSE
EXPERIENCE THAT CAN HELP
INVESTIGATORS NAVIGATE THIS
TOWARDS AN EYE -- HEADING
TOWARDS THE CLINICAL TRIALS THAT
WOULD BE FUNDED THROUGH OTHER
MECHANISMS?
>> THANKS FOR THE QUESTION.
IN OUR CONTRACTS, FOR EXAMPLE,
THE THERAPEUTIC RESEARCH PROGRAM
AND BASIC SCIENCES PROGRAM, WE
DON'T HAVE REGULATORY GUIDANCE,
PER SE, BUT WE DO HAVE OUR
CONTRACTORS THAT IN PARTICULAR
FIELDS, THEY CAN PROVIDE
REGULATORY -- WHAT IS REQUIRED
FOR, LET'S SAY, SAFETY
PHARMACOLOGY OR C & C.
PRETTY SURE THAT PREVENTION
SCIENCES PROGRAM MIGHT OFFER
REGULATORY SUPPORT SERVICES.
BULL WHAT IS IMPORTANT HERE, AND
W --BUT WHAT IS IMPORTANT HERE,T
WE ARE LOOKING AT IN THIS
PARTICULAR INITIATIVE, WE
HAVE OUR -- LIKE A PAR HERE THAT
24 PLANNING FOR PRODUCT DEVELOPT
STRATEGY, THIS IS ACTUALLY -- IT
WOULD BE A GREAT OPPORTUNITY FOR
INVESTIGATORS AND TO SIT A
SPECIFIC WAY WHILE REGULATORY
CONSULTANTS, OR A PART OF THE
TEAM, ARE VERY IMPORTANT.
SO THAT IS HAVING DESIGN THE
STRATEGIES TO ACTUALLY PROPOSE
WHAT IS NEEDED FOR THIS RFA AND
ACTUALLY WE DO -- AS ONE OF OUR
SCOPES HERE, IN THE SCOPE IS ONE
OF THE REGULATORY ACTIVITIES
INCLUDING PREIND MEETINGS WITH
THE FDA.
SO WE DO ANTICIPATE THAT THERE
WOULD BE REGULATORY CONSULTANT
OR IN ANY -- OR IT CAN BE THE
OFFICE OR A CONSULTANT, ONE THAT
PROVIDES REGULATORY -- AS A PART
OF THE TEAM.
I HOPE I ANSWERED YOUR QUESTION.
>> THANKS, IT'S PROBABLY JUST
WORTH SOME THOUGHT ABOUT THE
WORDING IN THE RFA ABOUT THAT
COMPONENT.
>> OKAY.
THANK YOU.
>> I DON'T SEE ANY ADDITIONAL
QUESTIONS.
THANK YOU VERY MUCH.
EVERYBODY PLEASE ENTER YOUR
VOTE, AND I'LL INTRODUCE KEITH
CRAWFORD, WHO'S GOING TO PRESENT
THE LAST CONCEPT.
OF THE DAY.
>> SO I'M THE PERSON STANDING
BETWEEN YOU AND HAPPY HOUR, SO
I'M GOING TO GET RIGHT INTO IT.
I'M KEITH CRAWFORD.
I'M A PROGRAM OFFICER IN THE
THERAPEUTICS RESEARCH PROGRAM,
AND I'M GOING TO PRESENT ON THE
VIROLOGY QUALITY ASSURANCE
PROGRAM.
AND THE OBJECTIVE OF THIS
PROGRAM IS TO PROVIDE
COMPREHENSIVE QUALITY ASSESSMENT
PROGRAM FOR THE DAIDS
LABORATORIES THAT PROVIDE
VIROLOGIC ASSAYS PRIMARILY FOR
HIV BUT OTHER VIRAL PATHOGENS IN
SUPPORTING THE DAIDS CLINICAL
RESEARCH PROGRAM.
THIS IS A REISSUE OF A CONTRACT.
IT'S A 7-YEAR CONTRACT AND THERE
WILL BE ONE AWARD.
SO DAIDS HAS AN ARAIL ARRAY OF Y
ASSURANCE PROGRAMS, SO IN
ADDITION TO THE VQA, WE HAVE THE
CPQA OR THE CLINICAL
PHARMACOLOGY QUALITY ASSURANCE
PROGRAM, WE HAVE THE IQA, THE
IMMUNOLOGY QUALITY ASSURANCE
PROGRAM.
WE HAVE THE TBQA, QUALITY
ASAWRASSURANCE PROGRAM THAT SUPS
TUBERCULOSIS RESEARCH, AND WE
HAVE A HOST OF OTHERS.
AND THESE ARE, YOU MIGHT SAY,
THE FRONT LINE OF OUR QUALITY
ASSURANCE PROGRAMS.
THE VIROLOGY QUALITY ASSURANCE
PROGRAM GOES ALL THE WAY BACK TO
1988.
RUSH UNIVERSITY HELD THE PRIOR
CONTRACT FOR OVER TWO DECADES,
AND THE CURRENT CONTRACT IS HELD
BY DUKE UNIVERSITY.
WE HAVE OVER 100 LABS THAT
PARTICIPATE IN THE V/Q A PROGRAM
ACROSS 30 COUNTRIES.
SO AGAIN, THE OVERVIEW.
PROVIDING QUALITY ASSURANCE AND
PROFICIENCY TESTING FOR
VIROLOGIC-BASED ASSAYS FOR HIV,
BUT ALSO OTHER PATHOGENS.
SO WE HAVE DONE PROFICIENCY
TESTING FOR HEPATITIS C RNA IN
THE PAST, AND WE ALSO DID SOME
VERY EARLY WORK WITH COVID-19 IN
DEVELOPING NEUTRALIZING ASSAYS
OR EXPLORING DIFFERENT
NEUTRALIZING ASSAYS.
IT'S KEY TO POINT OUT THAT THIS
PROGRAM IS ISO-ACCREDITED, WHICH
MEANS IT MEETS THE HIGHEST
STANDARD FOR EFFICIENCY TESTING
PROVIDERS.
IT IMPLEMENTS STANDARDS NOT JUST
FOR EXISTING ASSAYS, BUT IS ALSO
LOOKING AT THE EVOLUTION OF NEW
TECHNOLOGIES AND NEW PLATFORMS
FOR VIROLOGIC ASSAYS.
THE SUPPORT ASSAY VALIDATION
FROM THESE LABS, AND THEY ASSIST
THE LABS IN OPTIMIZING THEIR
ASSAYS.
AND THIS POINT I THINK IS REALLY
IMPORTANT, ENSURING THE VALIDITY
OF INTER- AND INTRA-LABORATORY
COMPARABILITY OF THE VIROLOGIC
LABORATORY DATA.
THIS IS REALLY KEY BECAUSE
MULTICENTER CLINICAL TRIALS
WHERE WE CAN TAKE DAY TA FROM
LABS ALL AROUND THE WORLD
BECAUSE WE KNOW THAT THOSE LABS
ARE PERFORMING THE ASSAYS AT THE
BEST QUALITY.
SO THE VQA HAS THREE PRIMARY
OPERATIONS.
WE HAVE THE QUANTITATIVE HIV RNA
OR VIRAL LOAD PROGRAM, WE HAVE
THE QUALITATIVE HIV NUCLEIC ACID
TESTING PROGRAM, AND WE HAVE THE
HIV DRUG RESISTANCE AND
SEQUENCING PROGRAM.
SO I'LL JUST TAKE A QUICK LOOK
AT THESE THREE PROGRAMS AND HOW
THEY WORK.
OF COURSE THE QUANTITATIVE IS
GOING TO ASSESS THE LAB'S
ABILITY TO DO VIRAL LOAD
TESTING.
THESE PT PANELS CAN BE PREPARED
IN PLASMA OR DRY BLOODSPOTS.
WE ALSO CAN PREPARE THEM IN CSF
AND MAY HAVE THE ABILITY TO
DEVELOP THEM AND OTHER MATRICES
SUCH AS BREAST MILK, FOR
EXAMPLE.
THE PANEL CONSISTS OF A RANGE OF
DIFFERENT CONCENTRATIONS OF
VIRAL RNA RANGING FROM VERY HIGH
CONCENTRATIONS TO CONCENTRATIONS
CLOSE TO THE LIMIT OF DETECTION
OF THE ASSAY.
THERE ARE A NUMBER OF
REPLICATES, SO THESE ARE
INTERSPERSED THROUGHOUT THE
PANEL IN A MANNER THAT IS
RANDOMIZED BUT IT'S BLINDED, OF
COURSE, TO THE LABS, AND THEY
HAVE TO CORRECTLY DETERMINE THE
CONCENTRATIONS IN THE PANEL.
THE QUALITATIVE NUCLEIC ACID
TESTING PROGRAM, AGAIN, THIS IS
TO DETECT TOTAL VIRAL NUCLEIC
ACIDS IN CLINICAL SAMPLES.
THIS PANEL IS PERFORMED
DIFFERENTLY.
SO WE TAKE A U1 CELL LINE THAT
HAS A KNOWN NUMBER OF COPIES OF
PROVIRAL DNA AND ANNE, AND THOSE
CELLS ARE DILUTED INTO
UNINFECTED PPMCs.
SO WE GENERATE A RANGE OF
CONCENTRATIONS OF THE DILUTED
CELLS, AND GERNTION THIS IS A
QUALITATIVE ASSAY, SO WE WANT TO
KNOW IS THE SAMPLE REACTIVE OR
IS IT NON-REACTIVE?
THIS IS PREPARED IN EITHER WHOLE
BLOOD OR DRIED BLOODSPOTS, AND
GLOBALLY WE HAVE 18 LABS THAT
ARE PARTICIPATING.
THE LABS ARE GOING TO GET TWO OF
THESE PANELS EACH YEAR.
AND THEN WE HAVE THE HIV DRUG
RESISTANCE OR SEQUENCING
PROGRAM, AND THE GOAL OF THIS IS
TO SHOW THE ABILITY OF THE LABS
TO IDENTIFY THE PRESENCE OF
MUTATIONS THAT ARE KNOWN TO
CONFER RESISTANCE TO
ANTIRETROVIRAL DRUGS.
MOST OF OUR LABS ARE DOING
SANGER SEQUENCING BUT WE DO HAVE
SOME LABS IN INCREASING NUMBERS
THAT DO NEXT GENERATION
SEQUENCING.
AND AGAIN, THE FOCUS IS THE POL
REGION CONTAINING RT, PR AND IN
GENES.
WE HAVE 53 LABS THAT
PARTICIPATE, INCLUDING SOME W HO
LABS.
THEY'RE SURVEILLANCE LABS.
AND THE LABS ARE GOING TO GET
TWO OF THESE -- WE HAVE A NUMBER
OF ISOLATES HERE, STOCK
CONCENTRATIONS, AND THEY
REPRESENT VARIOUS DIFFERENT
VIRAL SUBTYPES, AND YOU CAN SEE
SOME OF THESE ISOLATES HAVE A
NUMBER OF RESISTANCE MUTATIONS
SPANNING THE DIFFERENT TARGET
GENES.
SOME HAVE MORE THAN ONE MUTATION
IN ONE SITE, SOME ONLY HAVE A
SINGLE MUTATION.
THE VQA HAS A COLLABORATION WITH
THE KILL MAN JA KILIMANJARO CHRN
MEDICAL CENTER IN TANZANIA.
WE ESTABLISHED THIS
COLLABORATION SO WE COULD
PROVIDE MATERIALS THAT REFLECT
WHAT THE LABS ARE LIKELY TO SEE
WHEN THEY ENROLL PATIENT INS IN
THEIR CLINICAL STUDIES.
SO AS MANY OF YOU KNOW, TANZANIA
HAS A FAIRLY HIGH PREVALENCE OF
SUBTYPE A VIRUS, ALSO SUBTYPE D
VIRUS, AND SOME SUBTYPE C.
AND HERE'S JUST AN EXAMPLE OF
SOME OF THE SAMPLES THAT WE
RECENTLY RECEIVE FROM TANZANIA,
AND YOU CAN SEE HERE, THE
SUBTYPE DIVERSITY, ALMOST HALF
OF THESE ARE SUBTYPE A1, WE HAVE
A FEW SUBTYPE Cs, AND WE HAVE
COMMON -- REVERSE TRANSCRIPTASE
AND INTERGRACE, THESE ARE
MUTATIONS WE DON'T HAVE
CURRENTLY REPRESENTED IN OUR
REPOSITORY.
WE ALSO HAVE THE ABILITY TO
ENGINEER INFECTIOUS MOLECULAR
CLONES.
SO WE CAN ACTUALLY INTRODUCE
MUTATIONS INTO ANY OF THESE
SITES OF THE REVERSE
TRANSCRIPTASE REGION, THIS IS A
WAY THAT WE CAN ACTUALLY PUT
SPECIFIC TYPES OF MUTATIONS IN
THE MATERIAL THAT GOES INTO THE
PANELS.
I WANT TO JUST TAKE A COUPLE
SLIDES TO DESCRIBE A NEW PILOT
PROGRAM WHICH IS FOCUSED ON LABS
THAT DO MEASUREMENTS OF THE
RESERVOIR.
THIS IS A COLLABORATION WITH THE
MARTIN DELANEY COLLABORATIVE,
AND YOU HEARD MY COLLEAGUES
DIANE AND TANIA TALK ABOUT THE
MARTIN DELANEY EARLIER, SO YOU
KNOW MANY OF THESE LABS ARE
DOING RESERVOIR ASSAYS.
MANY OF THEM ARE DOING INTACT
PROVIRAL DNA ASSAYS.
BUT THERE ARE VARIATIONS IN HOW
THEY'RE DOING THESE ASSAYS, SO
THE QUESTION BECOMES, OKAY, HOW
DO WE INTERPRET THIS, HOW DO WE
COMPARE HOW THESE DIFFERENT
ASSAYS ARE PERFORMING.
SO ONE OF THE GOALS OF THIS
PILOT PROGRAM IS TO LOOK AT
RELATIVE ASSAY PERFORMANCE
ACROSS THE DIFFERENT LABS,
BENCHMARKING, LOOKING AT
INTERLAB REPRODUCIBILITY.
WE'RE ALSO HOPING TO ESTABLISH
WHAT ARE THE KEY METRICS THAT
WE'RE GOING TO USE TO EVALUATE
PERFORMANCE OF THESE ASSAYS BOTH
WITHIN AND BETWEEN THE LABS OVER
TIME.
SO THE ULTIMATE GOAL IS TO
DEVELOP A PROFICIENCY TESTING
PROGRAM THAT WE CAN USE WITH
LABS THAT ARE DOING PREUR
CLDOING PURECLINICAL RESEARCH AG
THE RESERVOIR.
THE RAVEN COHORT IS A REPOSITORY
OF PLASMA AND PBMCs THAT ARE
COLLECTED LONGITUDALLY FROM
PEOPLE LIVING WITH HIV THAT HAVE
BOTH SUBTYPE B AND SUBTYPE C
VIRUS THROUGH A COLLABORATION
WITH SOUTH AFRICA FOR THE
SUBTYPE C.
AND IT'S IMPORTANT TO UNDERSTAND
THAT THIS MATERIAL IS HIGHLY
PEDIGREED.
SO THE SAMPLES IN THIS
REPOSITORY HAVE BEEN ANALYZED
BLI QVOA CELL ASSOCIATED RNA,
INTACT PROVIRAL DNA OF DIFFERENT
ASSAYS TO MEASURE THE RESERVOIR.
WE THINK THIS IS IDEAL MATERIAL.
THIS FOCUSES ON PROVIRAL DNA AND
ITS VARIATIONS.
WHAT WOULD THE PANELS LOOK LIKE.
SO WE WOULD HAVE A PANEL OF
PBMCs FROM RAVEN REPOSITORY,
AND THIS WOULD COME FROM
INDIVIDUALS THAT HAVE BEEN
CHARACTERIZED TO HAVE A HIGH
RESERVOIR OR LOW RESERVOIR, THIS
WOULD ALL BE MIXED INTO A PANEL.
WE HAVE PGH >> TRUSTEE CROSBIE:
HAVE AN ANALYTICAL DELUSIONSERID
SERIAL DELUSIONS OF J-LAT CELLS,
DILUTED INTO NEGATIVE JURKAT
CELLS, SO WE HAVE THESE
DELUSIONS IN THIS PANEL THAT
HAVE BEEN SENT OUT TO A LAB,
BEING ANALYZED AS WE SPEAK, AND
WE SHOULD BE HAVING THE RESULTS
IN PERHAPS A MONTH.
EACH SITE WILL PERFORM THEIR
IPDA ASSAYS, SUBMIT THEIR DATA
TO THE VQA AND OUR AMAZING
STATISTICAL TEAM WILL LOOK AT
THE RESULTS AND TRY TO LOOK AT
PATTERNS OR SEE WHAT WE CAN
LEARN FROM THIS PILOT
INTERVENTION.
SO WE HAD TWO EXCELLENT
REVIEWERS FOR THIS PROJECT.
WE HAD DR. KEITH JEROME AT
UNIVERSITY OF WASHINGTON.
WE HAD DR. LISHOMWA NDHLOVU.
SOME OF THE COMMENTS FOCUSING ON
CROSS-SUBTYPE IPDAs IN OUR
PILOT THAT I'VE JUST DESCRIBED,
PILOTING IPDAs TOWARDS CERTAIN
TYPES OF VIRUSES.
THE RAVEN COHORT AS I POINTED
OUT CONTAINS MATERIAL FROM
SUBTYPES B AND C SO WE DO HAVE
MATERIAL FROM DIFFERENT
SUBTYPES.
BUT OUR PILOT PROGRAM IS GOING
TO START OUT FOCUSING ON SUBTYPE
B, BECAUSE EVERYBODY CAN DO
THAT, AGAIN, WE DON'T KNOW WHAT
DIRECTION THIS PILOT IS GOING TO
GO.
IT'S A PILOT SO WE'RE GOING TO
MINIMIZE THE VARIABLES, FOCUS ON
SUBTYPE B AND THEN WHEN WE SEE
WHAT TYPE OF RESULTS WE GET,
HOPEFULLY AT SOME POINT WE WILL
BE ABLE TO EXPAND AND LOOK AT
IPDAs THAT EITHER CAN BE USED
FOR ALL SUBTYPES OR SPECIFIC FOR
CERTAIN TYPES OF SUBTYPES.
A QUESTION CAME YOU THE ABOUT
LABS THAT PARTICIPATE IN V/Q A
VQA ANDWHAT TYPES OF CHALLENGEST
THEY HAVE.
INDEED SOME OF THE LABS DO HAVE
CHALLENGES IN PARTICIPATING.
THE VQA STARTS OUT BY VALIDATING
AND OPTIMIZING THE ASSAYS THAT
THESE LABS ARE USING.
THERE ARE A NUMBER OF
PRELIMINARY ASSESSMENTS THAT
LABS HAVE TO PARTICIPATE IN
BEFORE THEY BECOME FULL MEMBERS
OR PARTICIPANTS IN THE VQA
PROGRAM.
WHEN PANELS ARE SENT OUT, IF A
LAB FAILS A PANEL, THE VQA HELPS
WITH TROUBLESHOOTING AND MAKES
RECOMMENDATIONS AND THEY CAN GET
ANOTHER PANEL TO SEE IF THEY
CORRECTED THE PROBLEMS.
BUT IF THERE ARE LABS THAT
CONSISTENTLY HAVE PERFORMANCE
ISSUES, THEN THEY WILL HAVE TO
WITHDRAW FROM THE PROGRAM.
THE POINT IS RAISED ABOUT
WHETHER THE APPLICANTS FOR THE
CONTRACT SHOULD DEMONSTRATE THE
CAPABILITY FOR CONDUCTING NEW
VIRAL ASSAYS, SO THIS COULD BE
FOR EMERGING PATHOGENS, FOR
EXAMPLE, OR PANDEMIC RESPONSE,
OR JUST PIVOTING OR OPTIMIZING
ASSAYS TO HIV OR OTHER VIRUSES.
WE AGREE THAT THAT IS IMPORTANT.
THIS IS A KEY EVALUATION
CRITERIA WHICH WILL BE
IDENTIFIED IN THE SOLICITATION.
I WILL STOP THERE AND TAKE ANY
QUESTIONS.
THANK YOU FOR YOUR TIME.
>> THANK YOU VERY MUCH.
ARE THERE QUESTIONS IN THE ROOM?
GRACE?
>> HEY, KEITH.
LET ME JUST SAY, I LOVE THE VQA.
I INTERACT WITH THEM A LOT.
THEY ARE REALLY CRITICAL FOR THE
CLINICAL TRIALS NETWORK, AND
I -- FROM THE OLD DAYS WHERE WE
WENT AROUND TEACHING EVERYBODY
HOW TO DO QUANTITATIVE HIV RNA
TO NOW, IT HAS JUST BEEN
COMPLETELY TRANSFORMATIVE, AND
THEY CONTINUE TO HELP THE LABS
WITH THEIR VALIDATIONS, ET
CETERA.
HOWEVER, I DO THINK HAVING THE
VQA CREATE THE PROFICIENCY
PANELS AS THEY'RE DOING GIVEN
THAT WHO HAS STANDARDS, THERE'S
A LOT OF QUALITY PROVIDERS UP
THERE WHO HAVE STANDARD HIV,
RNA, DNA PANELS, I'M NOT SURE
THAT'S THE BEST USE OF THE VQA
RESOURCES.
THEY'VE DONE THIS FOREVER.
THEY WERE THE FIRST PEOPLE TO DO
THIS.
BUT I WOULD LIKE NOW TO SEE
THOSE RESOURCES MORE IN WHAT YOU
WERE DESCRIBING WITH THE
RESERVOIRS AND THE IPDA, SO THAT
THEIR RESOURCES FOR CREATING
PANELS, OBVIOUSLY I THINK THEY
SHOULD STILL DISTRIBUTE AND HELP
THE LABS COULD BE BETTER SPENT
ON MORE CUTTING EDGE PROGRAMS
WHERE WE DON'T HAVE QUALITY
ASSURANCE MATERIALS.
BUT GREAT PROGRAM.
>> WELL, THANK YOU VERY MUCH,
GRACE, AND CERTAINLY YOUR
GUIDANCE HAS BEEN WELL
APPRECIATED AND HAS HELPED US
OVER THE YEARS.
I THINK WHEN WE START
CONSIDERING THE QUESTION THAT
YOU'RE POSING, KEEPING IN MIND
THAT, AGAIN, THIS IS A GLOBAL
PROGRAM, SO THERE'S SOME
COUNTRIES THAT MAY STILL REQUIRE
SOME OF THE SERVICES THAT WE
PROVIDE, SO I THINK THAT'S ONE
WAY THAT WE NEED TO THINK ABOUT
THIS, BUT I THINK YOU'RE
ABSOLUTELY RIGHT, AND I THINK
THAT THE WORK THAT WE'RE DOING
WITH THE PILOT FOR THE RESERVOIR
ASSAYS IS AN EXAMPLE OF WHAT THE
VQA CAN DO.
THERE HAS BEEN SOME WORK THAT
THE VQA HAS DONE WITH SOME OF
THE SINGLE COPY ASSAYS, SO THIS
IS A DIRECTION THAT WE COULD GO.
ONE OF THE THINGS I THINK THIS
REALTHAT'S REALLY EXCITING ABOUR
QUALITY ASSURANCE PROGRAM IS WE
CAN PIVOT AND WE CAN FOLLOW THE
SCIENCE, SO WHEN WE AWARD THESE
CONTRACTS, WE'RE AWARDING THEM
TO TEAMS THAT HAVE THE PROPER
PERSONNEL AND RESOURCES TO GO IN
WHAT DIRECTION THAT THE SCIENCE
IS GOING IN.
SO WE HEAR YOU, AND AGAIN, WE
HAVE AN ADVISORY BOARD FOR THE
VQA AS WE DO FOR ALL OF OUR
PROGRAMS, SO THESE TYPES OF
SUGGESTIONS CAN BE MADE, AND WE
CAN FOLLOW THE SCIENCE.
THANK YOU FOR THAT QUESTION.
>> CINDY, I SEE YOUR HAND UP.
>> YEAH, SO THAT WAS A NICE
PRESENTATION.
I DO NOT DO THIS ASSAY, SO I
JUST WAS CURIOUS, YOU KNOW, WHAT
IS THE EXPERIMENTAL VARIATION
ACROSS LABS AND HOW DO YOU
DEFINE FAILURE?
HOW MUCH VARIATION IS THERE IN
THIS ASSAY THAT'S CONSIDERED
ACCEPTABLE?
>> RIGHT, SO THAT'S A GOOD
POINT, AND THAT'S GOING TO
DEPEND, EACH OF THESE ASSAYS
IS -- IT'S GOING TO VARY, BUT
THAT IS SOMETHING THAT IS
TRACKED VERY CAREFULLY BY OUR
STATISTICAL TEAM, SO EVERY TIME
WE SEND OUT A PANEL, ALL OF THE
DATA IS COLLECTED, ALL OF THE
PERFORMANCE IS TRACKED SO WE CAN
SEE IF LABS ARE PERFORMING
WITHIN WHAT IS THE ACCEPTABLE
RANGE FOR THAT PARTICULAR ASSAY,
SO ALL OF THAT IS TRACKED.
AND IF LABS GO OUTSIDE OF THAT,
THEN THEY MAY HAVE TO REPEAT THE
ASSAY OR MAY HAVE TO TWEAK HOW
THEIR ASSAY IS DOING OR DO SOME
PROBLEM SHOOTING, BUT THAT IS
SOMETHING THAT IS REGULATED VERY
CLOSELY.
AND AS I ALSO OVERSEE SOME OF
THESE OTH OTHER QUALITY ASSURANE
PROGRAMS, THE MECHANISM IS THE
SAME.
SO WE HAVE VERY SOLID
STATISTICAL SUPPORT TO MAKE SURE
THAT THE ASSAYS PERFORM WITHIN A
CERTAIN LIMIT.
I HOPE THAT ANSWERS YOUR
QUESTION.
>> ANY ADDITIONAL QUESTIONS?
OKAY.
I WANT TO MAKE SURE EVERYBODY
HAS VOTED.
KEITH, I THINK WE CAN -- THANK
YOU VERY MUCH.
>> THANK YOU.
YOU CAN GO TO HAPPY HOUR.
>> SO PLEASE VOTE FOR ALL THE
CONCEPTS.
>> SAVE AND SUBMIT THE VOTE, IT
WOULD BE APPRECIATED.
>> SUBMIT IS AT THE TOP OF THE
PAGE.
JUST WANT TO REMIND EVERYONE,
OUR NEXT MEETING IS ON MONDAY,
SEPTEMBER 9TH.
IT WILL BE IN THIS ROOM AGAIN.
BRING YOUR LUNCH, AND WE' IT WIL
ALSO BE HYBRID FORMAT.
I THINK IF THERE'S NOTHING
ELSE -- CARL, DO YOU HAVE --
>> THANK YOU ALL FOR YOUR
ATTENDANCE.
IT'S REALLY GREAT TO SEE
EVERYBODY, AND AFTER A
PRODUCTIVE MEETING.
USUALLY WE HAVE TIME FOR PUBLIC
COMMENT.
NO PUBLIC COMMENT REQUESTS WERE
RECEIVED.
SO WE ARE FREE TO ADJOURN.
>> SO LET'S ADJOURN THE MEETING. 4618 02:53:19,589 THANK YOU, EVERYONE.