I'D LIKE TO WELCOME EVERYONE TO
THE JANUARY MEETING OF THE
DIVISION OF AIDS, AIDS RESEARCH
ADVISORY COMMITTEE OR ARAC.
I'M KEN BREEDBERG FROM MASS BRES
GENERAL HOSPITAL.
WE HAVE A BUSY AGENDA WHICH WE
WILL STAY CLOSE TO THIS
AFTERNOON.
DR. DIEFFENBACH HAS ASKED ALL
THE PROGRAM DIRECTORS TO TALK
ABOUT SCIENCE FRAMING TALK FOR
THEIR PROGRAMS AND ALSO TO THINK
ABOUT SPECIFICALLY LESSONS
LEARNED FROM THE PANDEMIC AND WE
WILL HAVE TIME FOR DISCUSSION AT
THE END, SO THAT WILL BE
INFORMATIVE AND INTERESTING.
I ENCOURAGE PEOPLE TO PUT
COMMENTS INTO THE CHAT DURING
THE PRESENTATIONS, AND HOPEFULLY
WE WILL GET TO AS MANY OF THEM
AS WE CAN DURING THE DISCUSSION.
BEFORE WE GET STARTED, I'M
WONDERING IF SOMEONE ON THE
COMMITTEE COULD GIVE A MOTION --
I'D LIKE TO GIVE A MOTION TO
APPROVE THE MINUTES FROM OUR
SEPTEMBER MEETING.
ANYONE -- OKAY, ANYONE SECOND
THE MOTION?
>>SECOND.
>>THANK YOU.
SO THERE IS A MOTION TO APPROVE
THE MINUTES OF OUR SEPTEMBER
MEETING.
ANY DEBATE ABOUT THAT?
ALL IN FAVOR OF APPROVING THE
MINUTES?
ANYONE OPPOSED?
SEEING NO OPPOSITION THEN, THE
MINUTES FROM THE SEPTEMBER
MEETING ARE APPROVED.
THANK YOU VERY MUCH.
GREAT.
BEFORE I TURN IT OVER TO
DR. DIEFFENBACH, I WANTED TO
JUST TAKE ONE MOMENT, THIS IS MY
LAST MEETING AS CHAIR OF ARAC,
AND ON BEHALF OF -- THERE ARE
SEVERAL PEOPLE LEAVING THE
COMMITTEE.
DRS. AGARWAL, GUPTA, FRANK AND
MYSELF.
DR. DIEFFENBACH, I WANTED TO
THANK YOU, WE WANT TO THANK YOU
FOR THE OPPORTUNITY TO SERVE ON
ARAC AND REALLY TO WORK WITH YOU
AND EVERYONE IN THIS
EXTRAORDINARY DIVISION.
AS WE'VE TALKED ABOUT I THINK
MULTIPLE TIMES OVER THE PAST
SEVERAL YEARS, THE PROGRESS IN
HIV DISEASE OVER THE PAST FOUR
DECADES IS REALLY UNSURPASSED, I
THINK, IN WHAT HAS HAPPENED IN
MEDICINE DURING THAT TIME, BOTH
IN TERMS OF CLINICAL IMPACT AND
ALSO GLOBAL IMPACT, WHICH IS
REALLY LIKE NOTHING THAT I THINK
HAS BEEN SEEN IN THE HISTORY OF
MEDICINE.
AND YET HERE WE ARE WITH STILL A
TREMENDOUS AMOUNT OF WORK STILL
TO DO, DESPITE ALL OF THAT
PROGRESS, AND AS I THINK ABOUT
MY COLLABORATIONS AND ALL OF OUR
COLLABORATIONS WITH PEOPLE IN
THE DIVISION, WITH EVERYONE HERE
FROM THE DIVISION OF AIDS,
PEOPLE IN THE COMMUNITY WHO'VE
WORKED SO HARD, INVESTIGATORS,
THERE REALLY IS NOT ONLY A
TREMENDOUS AMOUNT THAT WE CAN
DO, BUT I'M CONFIDENT THAT THESE
SUCCESSES WILL CONTINUE, SO I
WANT TO THANK EVERYONE AND WE
REALLY LOOK FORWARD TO THIS
AFTERNOON'S MEETING AND TO MUCH
MORE PROGRESS IN PREVENTING AND
TREATING HIV IN THE YEARS TO
COME WITH ALL OF THE EFFORTS
FROM PEOPLE IN THE DIVISION AT
NIAID.
SO THANK YOU.
LET ME TURN IT OVER TO YOU,
DR. DIEFFENBACH, FOR THE
DIRECTOR'S REPORT.
>>THANK YOU, KEN, AND FOR YOUR
INCREDIBLY KIND REMARKS.
I THINK THE STRENGTH OF NIAID
AND DIVISION OF AIDS IS CENTERED
IN COMMUNITY.
THE COMMUNITY WE SEEK TO SERVE
AND THE RESEARCH COMMUNITY.
AND IT'S THAT WONDERFUL
COMBINATION OF ALL FEELING WE'RE
ON THE SAME PAGE, MOVING FORWARD
TO ADDRESS ALL THE THINGS WE CAN
POSSIBLY ADDRESS THROUGH
MEDICINE TO HELP BRING AN END TO
THE GLOBAL PANDEMIC.
SO I HAVE THIS CHANCE TO GIVE MY
DIRECTOR'S REPORT.
THIS IS GOING TO BE A LITTLE BIT
DIFFERENT TODAY BECAUSE WE'RE
SPENDING A LOT OF TIME IN OUR
SESSION TODAY TALKING ABOUT
LESSONS LEARNED, BOTH POSITIVE
AND NEGATIVE, FROM SARS-COV-2.
SO SOME OF THE THINGS YOU WILL
USUALLY EXPECT TO SEE FROM ME
ARE PUT OFF UNTIL THE MAY
MEETING.
SO LET'S GO AHEAD AND GET
STARTED.
NEXT SLIDE, PLEASE.
SO KEN HAS ALREADY STOLEN SOME
OF MY THUNDER.
I WANT TO THANK THE FOLLOWING
PEOPLE.
RITU AGARWAL.
IAN FRANK.
ANITA GUPTA AND LAST BUT NOT
LEAST KEN, YOU HAVE A SUITABLY
SIGNED CERTIFICATE SUITABLE FOR
FRAMING, IT SHOULD BE ON YOUR
WAY TO YOUR OFFICES.
SO AGAIN, THANK YOU ALL FOR
PARTICIPATING AND BEING PART OF
JUST BEING THERE FOR US.
WE DO MORE THAN OTHER DIVISIONS
IN TERMS OF ENGAGING OUR
COMMITTEE, AND WE THINK IT PAYS
OFF.
I'D ALSO LIKE TO ANNOUNCE THAT
WE'VE HIRED ANDREW VERNON AS
CHIEF OF THE TB CLINICAL
RESEARCH BRANCH.
ANDY COMES TO US FROM CDC, WHERE
HE WAS A DRIVER IN THE TB
CLINICAL TRIALS GROUP AT CDC.
THIS IS A REALLY GOOD FIT FOR
US, AND WE LOOK FORWARD TO
REALLY DOING MORE IN TB
THERAPEUTICS AND VACCINES IN THE
NEAR FUTURE.
SO WELCOME, ANDY.
SO I WANT TO GO TO THE BUDGET
UPDATE.
THOSE OF YOU THAT WERE ON FOR
HUGH'S PRESENTATION HAVE SEEN
THIS ALREADY.
NEXT SLIDE, PLEASE.
THE WHITE HOUSE IS NOT DUE TO
ANNOUNCE THE BUDGET UNTIL LATER
THIS WEEK OR MAYBE NOT UNTIL WE
GET TO THE STATE OF THE UNION.
SO WE DO NOT KNOW WHAT'S IN THE
'24 PRESIDENT'S BUDGET.
BUT WE DO KNOW WHAT WAS IN THE
'23 BUDGET.
WE'VE SEEN THESE NUMBERS, NIAID
RECEIVED SLIGHTLY LESS THAN
3% -- A LITTLE LESS THAN 4%
INCREASE, BUT PLEASE NOTE ON
THIS SLIDE THAT THE AIDS
ALLOCATION IS NOT INCLUDED IN
THIS TOTAL.
AND THE OAR HAS NOW TAKEN THE
AIDS INCREASE AND DIVIDED IT UP
AMONG THE INSTITUTES, AND WE ARE
SET TO, AS A DIVISION, TAKE FULL
ADVANTAGE OF THE BUDGET INCREASE
THAT THE CONGRESS GAVE TO THE
OAR.
SO WE HAVE THE ESTABLISHED
PAYLINE HAS GONE FROM THE TENTH
TO THE 11TH PERCENTILE.
WE NEVER RESTRICT OR
DOWN-NEGOTIATE NONCOMPETING OR
COMPETING GRANTS OR CONTRACTS.
CERTAIN RESEARCH INITIATIVES
WILL BE CUT UP TO 20%, AND WE
ESTIMATE A SUCCESS RATE BETWEEN
18 AND 22 FOR THE ENTIRE
INSTITUTE.
SO SOME UPDATES IN TERMS OF THE
SCIENTIFIC PROGRAMS AND OTHER
ACTIVITIES.
SO THIS WAS DISAPPOINTING NEWS
IN SOME WAYS SOMEWHAT EXPECTED
BECAUSE OF THE COMPANION TRIAL
TO THE MEN'S TRIAL MOSAICO TRIAL
ENDED EARLY UNDER THE SAME
CIRCUMSTANCES, SO BASED ON THE
DSMB RECOMMENDATION, MOSAICO HAS
BEEN DISCONTINUED, STUDY
PARTICIPANTS HAVE BEEN NOTIFIED,
AND THE FINDINGS ARE MOVING
QUICKLY TOWARD PUBLICATION AND
RELEASE.
I THINK IT'S IMPORTANT FOR YOU
TO SEE JUST HOW FLAT THIS WAS.
THERE WERE, AT THE END, AN EQUAL
NUMBER OF INFECTIONS IN BOTH
ACTIVE AND PLACEBO, AND YOU CAN
SEE IT TRACKED THE SAME ALL THE
WAY ALONG.
SO AT NO POINT WAS THERE
EVIDENCE OF A SIGNAL THAT WANED
LIKE WE SAW WITH RV144.
IT WAS JUST PLAIN FLAT.
AS HUGH MENTIONED, THE TOTALLY
FRIGHTENING ISSUE THAT WE SAW IN
THIS TRIAL, ONE IS THE STUDY
PARTICIPANTS IN PLACEBO AND
VACCINE ARM HAD A MATCHED
INCIDENCE OF A LITTLE OVER 4%,
WHICH IS REALLY PROBLEMATIC.
REMEMBER THIS IS IN MEN IN
EUROPE, SOUTH AMERICA, AND THE
UNITED STATES, BASICALLY GLOBAL.
AND THIS IS A POPULATION THAT
HAD ACCESS TO PREP.
I THINK THE CHALLENGE WE FACE
GOING FORWARD IS HOW CAN WE
REACH THESE UNREACHABLE PEOPLE
AND PROVIDE THEM THE NECESSARY
SERVICES TO PREVENT ACQUISITION
OF HIV.
ON A MORE POSITIVE NOTE, THE
U.S. PREVENTION SERVICES TASK
FORCE HAS GIVEN THE LONG-ACTING
INJECTABLE OF CA APRETUDE GRADE,
AND THIS IS NOW GOING TO MOVE
THROUGH THEIR PROCESS OF GETTING
VALIDATED AS A GRADE A, WHICH
WILL HOPEFULLY LEAD WITHIN A
YEAR OR TWO TO FULL COVERAGE OF
THIS PREVENTION OPTION UNDER THE
ACA-APPROVED HEALTH PLANS,
BECAUSE THAT IS PART OF THE
LEGISLATION, IS THAT PREVENTION
SERVICES OF GRADE A OR B ARE TO
BE MADE ROUTINELY AVAILABLE.
SO THIS IS A BIG STEP FORWARD.
IT'S IMPORTANT TO NOTE THAT TDF
FTC WAS APPROVED BY THE FDA IN
2012.
IT TOOK THE PREVENTION SERVICES
TASK FORCE ALMOST SIX YEARS
BEFORE THEY GAVE PREP -- ORAL
DAILY PREP A GRADE OF A.
SO THIS IS A BIG STEP FORWARD
FOR USPSTF.
SO NOW I'M GOING TO SPEND SOME
TIME GOING OVER WHAT THE
DIVISION HAS BEEN THROUGH FOR
THE RESPONSE TO THE SARS-COV-2
PANDEMIC.
AND MY ROLE IN THIS IS TO SET
THE STAGE OF THE BIG PICTURE
VIEW OF WHAT WE AS A DIVISION
TACKLED IN TERMS OF WHERE WE
NEED TO THINK ABOUT WHAT WE'VE
DONE RIGHT AND WHAT WE NEED TO
IMPROVE.
IT'S ALSO IMPORTANT TO NOTE THAT
MOST OF THE OFFICES AND PROGRAMS
WILL DEVOTE TIME IN THEIR
PRESENTATIONS TODAY TO THIS
TOPIC.
VIRTUALLY EVERY OFFICE AND
PROGRAM PLAYED A ROLE IN THE
COVID RESPONSE, AND SO TODAY
WHILE WE'RE FOCUSING ON THE
CLINICAL ACTIVITIES, WE REALLY
WANT TO TAKE A STEP BACK AND
HIGHLIGHT THE FACT THAT SO MANY
OF THE BASIC RESEARCH VIROLOGY
LABS ALSO MADE TREMENDOUS
CONTRIBUTIONS TO THE SARS-COV-2
PANDEMIC.
LIKE CLINICAL SITES PIVOTING TO
WORK ON COVID.
MANY OF OUR PRE-CLINICAL AND
BASIC RESEARCH VIROLOGY LABS
ALSO PIVOTED AND BECAME, IN MANY
WAYS, THE CORNERSTONE OF
ANSWERING THE QUESTIONS IN
CORONAVIRUS BIOLOGY.
SO THROUGH THEIR EFFORTS, THE
DIVISION REALLY HAD A
TWO-PRONGED ATTACK.
ON
SARS-COV-2.
ONE ARM DEFINING THE BASIC ARMS
OF I MU NOLG, VIROLOGY, AND THE
SECOND PLAYING PIVOTAL ROLES IN
DEVELOPING VACCINES,
THERAPEUTICS AND MONOCLONAL
ANTIBODIES TO PREVENT AND TREAT
SARS-COV-2.
SO I'M GOING TO FOCUS MY REMARKS
FROM NOW ON ON THE ISSUES AROUND
THE CLINICAL, SO YOU CAN SEE
WHAT WE DID.
BUT I REALLY WANTED YOU TO
UNDERSTAND THAT REALLY WE HAD A
INFLUENCE ACROSS THE ENTIRE
SPECTRUM OF RESEARCH ACTIVITIES.
SO EARLY ON, IN APRIL OF 2020,
THE NIH LAUNCHED THE ACTIVE
PROGRAM, ACCELERATING COVID
THERAPEUTIC INTERVENTIONS AND
VACCINES, THE MISSION OF WHICH
WAS TO DEVELOP COORDINATED
RESEARCH RESPONSE TO SPEED
TREATMENT AND VACCINE OPTIONS
FOR CORONAVIRUS DISEASE.
SO THERE WERE ABSOLUTELY SOME
CRITICAL AREAS THAT WERE
TACKLED.
THERE WAS A VACCINE GROUP, A
PRE-CLINICAL GROUP, A CLINICAL
TRIALS CAPACITY GROUP, AND
THERAPEUTICS, CLINICAL
THERAPEUTICS GROUP THAT WERE ALL
FORMED THAT DEALT WITH
EVERYTHING FROM VACCINE CLINICAL
TRIALS, EVALUATION IN ANIMAL
MODELS, SURVEYING CLINICAL TRIAL
NETWORK INVENTORY, BUT ALSO
MASTER PROTOCOLS TO EVALUATE
THERAPEUTIC.
SO GRAPHICALLY ACTIL LOOKS LIKE
THIS.
THERE WERE SUBGROUPS, THERE'S
ACTIV 1-6.
ACTIV 2 WAS RUN LARGELY BY THE
TREATMENT -- THE THERAPEUTICS
RESEARCH PROGRAM IN
COLLABORATION WITH THE AIDS
CLINICAL TRIALS GROUP THAT
EVALUATED AGENTS INCLUDING A
NUMBER OF MONOCLONAL ANTIBODIES
AND ARE CURRENTLY WORKING IN
ACTIV2 TO EVALUATE THE PROTEASE
INHIBITOR.
ACTIV3 WAS LARGELY LED BY CLIFF
LANE'S GROUP.
YES, THAT'S WHAT WE'RE FOCUSED
ON.
AND PETER WILL TALK ABOUT THIS
AT LENGTH.
AS WILL MANA SHEA AND CAROL WHO
WERE ESSENTIAL PARTNERS IN TERMS
OF DEVELOPMENT OF SITES AND THE
REGULATORY OVERSIGHT OF THESE
TRIALS.
SO THIS IS THE MASTER PROTOCOL.
AGENTS CAME IN AT THE PHASE
2 LEVEL AFTER BEING SELECTED BY
THE AGENT SELECTION COMMITTEE.
WE HAD OVER 200 CLINICAL TRIAL
SITES.
THEY WERE SMALL PHASE 2s WHERE
WE LOOKED AT, THROUGH THE DSMB,
APPROXIMATELY 110 PEOPLE AND IF
THE AGENT SHOWED PROMISE, IT
KEPT ON GOING INTO PHASE 3.
IF IT DIDN'T, ACTIVITY WAS
ENDED.
WE WERE THE REGULATORY SPONSOR
FOR ACTIV 2 AND THE ULTIMATE
GOAL WAS TO GET BETTER THERAPIES
TO ADVANCE TO EMERGENCY USE
AUTHORIZATION.
THE PARALLEL TRACK ON THE
VACCINE AND MONOCLONAL ANTIBODY
SIDE WAS THE NETWORK FORMED BY
NETWORKS FROM WITHIN THE
DIVISION OF AIDS, THE HVTN, THE
HPTN, AND THE IDCRC NETWORK IN
DMID, WHICH IS THEIR INFECTIOUS
DISEASE NETWORK.
AND THEIR PLATFORM WAS SIMILAR.
THEY HAD HARMONIZED -- THEY
WANTED HARMONIZED EFFICACY
TRIALS WITH THE COLLABORATING
CLINICAL TRIALS NETWORKS.
THEY HAD LABORATORIES THAT
LOOKED AT EVERYTHING AT THE
ANTIBODY RESPONSES AS WELL AS
T-CELL RESPONSES, AND THAT WAS A
PARTICULAR PLATFORM THAT ALSO
ENGAGED BARDA AND THE BRC IN
TERMS OF SETTING UP THE
QUALIFIED ASSAYS FOR MEASURING
RESPONSES.
WE HAD AN INTEGRATED DATA SAFETY
MONITORING BOARD THAT OVERSAW
ALL THE VACCINE TRIALS, AND THE
WAY THE DATA WAS BEING
COLLECTED, WE HAD THE ABILITY
THEN TO LOOK BETWEEN TRIAL
STATISTICAL GROUP CORRELATES OF
PROTECTION.
THIS WAS A REALLY AMAZING TEAM
LIKE THE ACTIV 2 TEAM.
THESE WERE THE PRODUCTS THAT
WERE EVALUATED.
WE WORKED ON THE MODERNA
VACCINE, AND THAT RECEIVED EUA
ALL THE WAY DOWN TO SIX MONTHS.
JANUARY 16, THE EUA HAS BEEN
ISSUED AND IT AVAILABLE 18 AND
UP.
ASTRAZENECA WAS EVALUATED AND
WHILE IT WASN'T AUTHORIZED IN
THIS COUNTRY, IT WAS AUTHORIZED
IN OVER 89 COUNTRIES.
NOVAVAX MOVED FORWARD AND HAS
RECEIVED AN EUA.
THE ONE THAT IS STILL IN THE
PROCESS OF COMPLETING THEIR
CLINICAL TRIAL IS THE GSK SANOFI
PROTEIN, AND THAT IS STILL
ONGOING.
SO WITH THAT, I WILL SWITCH
GEARS NOW AND TALK ABOUT THE
SBIR CONTRACT TOPICS THAT WE
BRING FORWARD TO YOU FOR
APPROVAL EVERY JANUARY.
SO LET ME GO TO THE NEXT SLIDE,
PLEASE.
WE HAVE FOUR TOPICS TODAY.
THESE ARE DESIGNED TO COMPLEMENT
THE GRANT PROGRAMS THAT ARE
FUNDED COMPETITIVELY EACH YEAR.
REMEMBER, SBIR MONEY IS A
CONGRESSIONALLY MANDATED
SETASIDE THAT COMES OFF THE TOP
OF THE NIH BUDGET RUNNING 2 1/2%
PER YEAR.
SO IT IS IMPORTANT THAT THE TI
DIVISION FIGURE OUT HOW TO USE
THESE ESSENTIALLY SETASIDE
DOLLARS AS EFFECTIVELY AS
POSSIBLE.
ONE WAY WE CAN DO THAT IS
THROUGH THESE CONTRACT
SOLICITATIONS.
SO WE HAVE FOUR TOPICS AS I
SAID.
FIRST TOPIC, LOOKING AT
IMPROVING DELIVERY OF BROAD
NEUTRALIZING MONOCLONAL
ANTIBODIES.
CAN DEVICES OR MATERIALS BE
DEVISED TO EASE AND IMPROVE THE
DELIVERY OF NEUTRALIZING
ANTIBODIES?
WHILE THIS IS FOCUSED FROM OUR
PERSPECTIVE ON HIV-DIRECTED
NEUTRALIZING MONOCLONAL
ANTIBODIES, THOSE OF YOU WHO SAW
"THE WASHINGTON POST" THIS
MORNING, CAROLYN JOHNSON HAD A
VERY INTERESTING ARTICLE ON THE
IMPACT OF MONOCLONAL ANTIBODIES
IN INFECTIOUS DISEASE RESEARCH
WRIT LARGE.
SO THIS IS A VERY IMPORTANT
TOPIC THAT HAS EVENTUALLY --
GENERALIZABLE ACROSS THE
SPECTRUM OF DISEASES, INCLUDING
MALARIA, AS YOU SAW IF YOU
LOOKED AT THAT ARTICLE.
SO YOU CAN SEE THE GOAL IS TO
DEVELOP MATERIALS THAT CAN
SUSTAIN DELIVERY OF MONOCLONAL
ANTIBODIES.
SO THE KINDS OF ACTIVITIES THAT
ARE ALLOWED ARE OPTIMIZATION OF
FORMULATION IN PHASE ONE AND
THEN PROOF OF CONCEPT TESTING IN
RELEVANT ANIMAL MODELS
ESTABLISHING QA/QC METHODOLOGY
FOR DEVELOPING BNAB
FORMULATIONS, BUT ULTIMATE GOAL
IS TO PREPARE A REGULATORY
PACKAGE FOR NEXT STEPS OUT OF
THIS CONTRACT.
SO THAT'S TOPIC ONE.
TO PICK 2 IS ONE THAT WE THINK
IS CRITICALLY IMPORTANT AND
WOULD REALLY LIKE TO SEE
INDUSTRY JUMP INTO THIS.
IF YOU THINK ABOUT WHAT WE
ALREADY KNOW ABOUT DIRECT ACTING
ANTIVIRALS FOR HEPATITIS C, WE
KNOW THAT ORAL MEDICATION
DELIVERED FOR ANYWHERE BETWEEN C
AT A LEVEL OF BETWEEN 95 AND
100%.
WE SHOULD BE ABLE, THROUGH OUR
EXPERIENCE WITH LONG-ACTING
MEDICINES, TO BE ABLE TO COME UP
WITH A ONE-DOSE CURE, ONE-DOSE
TREATMENT FOR HEPATITIS C SO
THAT'S OUR FUNDAMENTAL GOAL IN
THIS PROJECT, IS TO DEVELOP SAFE
AND SUSTAINED DELIVERY THAT CAN
ESSENTIALLY BE ONE SHOT OR ONE
PATCH OR ONE DELIVERY METHOD
THAT COULD BE DEPLOYED IN REMOTE
SETTINGS, WOULD MITIGATE ANY
DRUG RESISTANCE OR
NONCOMPLIANCE, BUT IT WOULD
REALLY SIMPLIFY AND HELP US GET
CLOSER TO THE ABILITY TO USE THE
MEDICATIONS TO ERADICATE
HEPATITIS C AGAIN, SO THE IDEA,
THE LONG-RANGE GOAL OF THIS IS
DEVELOP THE CONCEPT AND REALLY
ENGAGE IN IND-DIRECTED
PHARMACOLOGY AND TOXICOLOGY IN
SUITABLE ANIMAL M MODELS THAT WL
GIVE US THIS KIND OF SUSTAINED
RELEASE THAT WILL GIVE US THE
ABILITY TO, THROUGH THESE --
THIS ADVANCE, TREAT AND CURE
HEPATITIS C AS EFFECTIVELY AS WE
CAN WITH ORAL MEDICATIONS.
NEXT, AN AREA THAT'S REALLY
CRITICAL FOR HIV CURE, JUST IN
GENERAL, IS BEING ABLE TO HAVE
REALLY RAPID DIAGNOSTIC ASSAYS
FOR ACUTE HIV AND/OR REBOUND.
ONE OF THE QUESTIONS WE GET ALL
ALONG IN STRUCTURED TREATMENT
INTERRUPTION IS HOW AM I GOING
TO KNOW IF I'M REBOUNDING.
SO BY DEVELOPING THESE KINDS OF
TOOLS THAT WOULD ALLOW STUDY
PARTICIPANTS AND JUST PATIENTS
IN GENERAL TO MONITOR THEIR
VIRAL LOAD ON THEIR OWN, THIS
COULD BE A POTENTIAL GAME
CHANGER TO HELP PEOPLE STAY VEER
LOGICALLY SUPPRESSED IF THEY'RE
ON MEDICATION AND/OR
PARTICIPATING IN RESEARCH
PROTOCOLS.
SO THERE'S BEEN SOME WORK DONE
IN THIS AREA ALREADY.
WE WANT TO EXPAND PROTOTYPE
ASSAYS, DEVELOP PROCESS CONTROLS
FOR SUCH KITS THAT FACILITATE
COMMERCIALIZATION.
IN PHASE TWO, HAVE THE TEAM
DEVELOP PRODUCT DEVELOPMENT AND
REGULATORY STRATEGIES FOR
APPROVAL AND DEMONSTRATION OF
CLINICAL APPLICATION, AND
FINALIZATION OF A COMMERCIAL
PLAN.
AND LAST BUT NOT LEAST, THE
FORTH ONE IS, IN ANOTHER FORM OF
IMPROVED DIAGNOSTIC, WE HAVE
AROUND THE GLOBE PEOPLE THAT ARE
LIVING WITH MULTIPLE VIRUSES,
INCLUDING HEPATITIS B, HEPATITIS
C AND HIV.
IT WOULD BE REALLY GOOD TO HAVE
A PATIENT-ADMINISTERED
DIAGNOSTIC ALLOWING FOR THE
DETECTION OF THESE THREE VIRUSES
SIMULTANEOUSLY.
I THINK THIS WOULD BE A
POTENTIAL GAME CHANGER FOR THE
WORLD, AND SOMETHING THAT WE
WOULD LIKE TO SPEND SOME TIME
AND ENERGY FOSTERING.
AND REALLY AT THE END OF THE
DAY, IT IS ABOUT DEMONSTRATING
THE CLINICAL SENSITIVITY AND
SPECIFICITY OF SUCH A DEVICE FOR
SELF-COLLECTED SPECIMENS.
WE WANT THERE TO BE A MARKET
ASSESSMENT AND COST-EFFECTIVE
ANALYSIS AND DEVELOP THE TESTING
WORK FOR SPECIFIC PRODUCT
INDICATION.
SO THAT'S MY PRESENTATION.
WHILE YOU'RE CASTING YOUR VOTES,
KEN, WHY DON'T WE OPEN THE FLOOR
TO QUESTIONS COVERING MY TALK.
>>YES, THANK YOU,
DR. DIEFFENBACH, AND PLEASE,
EVERYONE ON THE COMMITTEE, IF
YOU COULD OPEN YOUR ECB, GO TO
THE DAY'S ARAC TAB DOWN ABOUT A
THIRD OF THE WAY TO THE VOTING
MATERIALS OPEN SESSION, AND
THOSE FOUR TOPICS ARE THERE.
CERTAINLY WOULD BE EXCITING TO
BE ON THE OTHER SIDE OF THESE
AND HAVE THOSE DEVELOPED.
QUESTIONS FOR CARL OR COMMENTS
ON THESE TOPICS OR OTHERS?
>>CARL, I HAD A QUESTION ABOUT
THE LONG-ACTING -- OR THE
DELIVERY OF THE BNABs.
YOU SAID FOR HIV BUT I THOUGHT
YOU ALSO SAID THERE'S SOME
RELEVANCE TO OTHER VIRUSES, SO
EXPLAIN THAT TO ME.
ARE YOU --
>>SO I'M SAYING -- THAT'S A
GOOD POINT.
SO BECAUSE THIS IS THE DIVISION
OF AIDS, OUR FOCUS IS ON
BNABs, BUT ANYTHING WE LEARN
IN THIS SPACE WILL BE APPLICABLE
FOR OTHER INFECTIOUS DISEASES.
THAT WAS MY POINT.
>>OKAY.
THANK YOU.
>>I HAVE A QUICK QUESTION,
CARL.
VERY EXCITING IDEA OF A SINGLE
TEST OR PLATFORM FOR HIV, HBV
AND HCV.
MOST OF THE VALUE OF A TEST IS
POTENTIALLY FOR TREATMENT OF
THOSE ILLNESSES, ALTHOUGH
PREVENTION COULD BE ALSO
NOTABLE.
SO I GUESS I'M WONDERING ABOUT
PEPFAR AND OTHER ORGANIZATIONS
WITH A COMMITMENT TO TREAT HBV
AND HCV, WHERE WE'VE REALLY HAD
A FOCUS ON HIV.
SO HAS THAT BEEN CONSIDERED IN
TERMS OF THE DOWNSTREAM IMPACT
OF HAVING THIS TEST AVAILABLE?
>>WELL, AGAIN, YOU'RE THINKING
IN VERY SIMILAR WAYS THAT WE
HAVE BEEN THINKING.
WE ALREADY KNOW WE HAVE GOOD
TREATMENT FOR HEP C.
WE ARE VERY EXCITED BY WHAT WE
SEE IN THE HBV DRUG DEVELOPMENT
AND TREATMENT STRATEGIES, AND SO
WHAT TO HELP BE A DISRUPTIVE
INNOVATION, TO HELP BRING THESE
MEDICATIONS ALONG, THAN A SIMPLE
TEST THAT COULD BE USED
CLINICALLY.
SO THERE IS SOME METHOD TO OUR
MADNESS.
SO THANK YOU.
>>GREAT.
GREAT.
MONICA.
>>I RECOGNIZE THIS IS DAIDS,
BUT IT IS EXCITING, MONOCLONAL
ANTIBODIES ARE IMPORTANT,
BNABs ARE IMPORTANT, BUT THE
EVUSHELD FOR SARS-COV-2
PROPHYLAXIS JUST GOT TAKEN OFF
THE FDA LIST LAST WEEK BECAUSE
OF THE EMERGENCE OF THESE NEW
VARIANTS AND SUBVARIANTS, AND WE
ACTUALLY HAVE NO MONOCLONAL
ANTIBODIES NOW TO TREAT OR
PREVENT SARS-COV-2.
>>SOTROVIMAB IS COMING BACK
SOON.
>>OKAY.
REALLY.
OKAY.
THAT IS MY QUESTION, IS THAT CAN
WE -- DESPITE THE PANDEMIC
PREPAREDNESS AND ALL THAT NOT
BEING ADEQUATELY FUNDED, CAN WE
CONTINUE TO SUPPORT AND WORK ON
MONOCLONAL ANTIBODIES FOR ALL
INFECTIOUS DISEASES INCLUDING
SARS-COV-2?
>>THAT'S A QUESTION THAT GOES
TO IN THE DMID SESSION, IF YOU
WERE SITTING OVER THERE
LISTENING TO EMILY'S GROUP, YOU
WILL HEAR THAT THEY ARE
INTERESTED IN SUPPORTING
MONOCLONAL ANTIBODY DEVELOPMENT
FOR DISEASES IN THE FUTURE.
THE VRC HAS BEEN COMMITTED TO
THIS AS WELL, DEVELOPING A
MALARIA MONOCLONAL AND ALSO
MONOCLONALS FOR VIRUSES LIKE
EBOLA AND MARBURG, THINGS LIKE
THAT.
SO I THINK THE INSTITUTE IS
COMMITTED TO MONOCLONAL
ANTIBODIES AS WELL.
>>WE'LL TAKE ONE MORE QUESTION.
KEITH.
>>CARL, FOR SUBJECTS THREE AND
FOUR, THE SBIR, THE PATIENT
ADMINISTERED DIAGNOSTIC HAS
OBVIOUSLY BEEN CRITICAL AND VERY
SUCCESSFUL IN THE COVID
RESPONSE, BUT THE FLIP SIDE IS
OF COURSE WE HAVE NO IDEA HOW
MANY INFECTIONS THERE REALLY
ARE.
SO IS THAT REPORTING ISSUE SORT
OF PART OF WHAT YOU'RE THINKING
ABOUT HERE IN THAT?
IN OTHER WORDS, ARE THESE JUST
REALLY JUST -- YOU KNOW, IDEALLY
AN LFA WHERE YOU THROW IT AWAY
WHEN YOU'RE DONE, OR ARE THESE
SOMETHING WHERE YOU'RE HOPING
THAT THERE WILL BE SOME SORT OF
REPORTING OR CONNECTION WITH THE
HEALTHCARE SYSTEM?
>>THAT NEEDS TO BE WORKED OUT.
THE GOOD THING IS CORONAVIRUS DO
HAVE THESE OTHER CIRCUIT MARKERS
CALLED HOSPITALIZATIONS AND
DEATHS.
WE KNOW -- I REALIZE THEY'RE LAG
INDICATORS BUT IT'S NOT LIKE
WE'RE COMPLETELY IN THE DARK.
>>YEAH, BUT -- ALL RIGHT, THE
CURE TRIAL, THAT'S NOT GOING
TO -- YOU KNOW, RIGHT?
>>EXACTLY.
>>YOU MISS PEOPLE THAT COME IN
WITH HIV.
>>I THINK YOUR POINT IS FOR THE
SELF-TESTING FOR HIV, YOU WOULD
IDEALLY WANT THERE TO BE A
HEALTHCARE SYSTEM BUILT AROUND
THAT CURE PATIENT THAT IF THEY
DID TEST POSITIVE, THEY HAD A
1-800 NUMBER OR WAY OF REACHING
OUT IMMEDIATELY TO REINITIATE
THERAPY, GO IN AND GET A BLOOD
TEST, ALL OF THAT, SO YOU GOT A
SENSE.
BUT I THINK THAT HAS TO BE BUILT
INTO THE SYSTEM FOR THOSE KINDS
OF TISES.
OF TESTS.
>>GREAT.
THANK YOU, DR. DIEFFENBACH.
WE WILL TURN NOW TO DR. MAUREEN
GOODENOW, DIRECTOR OF THE OFFICE
OF AIDS RESEARCH, FOR THE OFFICE
OF AIDS RESEARCH REPORT.
THANK YOU, DR. GOODENOW.
>>WELL, THANK YOU VERY MUCH.
LET ME JUST GET MY MATERIALS UP
HERE.
I'M ASSUMING YOU CAN HEAR ME.
>>WE CAN.
YES.
>>OKAY.
WELL, THANK YOU.
I'M VERY HAPPY TO BE HERE TODAY
TO PROVIDE AN OVERVIEW OF THE
NEW AND EXCITING INITIATIVES AT
THE OFFICE OF AIDS RESEARCH.
OAR WAS ESTABLISHED 35 YEARS AGO
WITH THE LEGISLATIVE MANDATE TO
CONVENE PARTNERS ACROSS NIH
INSTITUTES, CENTERS AND OFFICES,
FEDERAL AGENCIES AND COMMUNITY
GROUPS FOR A ROBUST AGENDA IN
HIV RESEARCH.
THE GOAL WAS AND CONTINUES TO BE
TO END THE HIV PANDEMIC.
THE NEXT SLIDE.
OVER THE PAST 40 YEARS, OUR WORK
ADDRESSING THE HIV PANDEMIC HAS
EVOLVED IN SIGNIFICANT WAYS.
THE INITIAL RESEARCH FOCUS ON
HIV PATHOGENESIS EXPANDED
TOWARDS HIV DIAGNOSIS,
TREATMENT, PREVENTION, CURE, AND
IMPROVING THE HEALTH OF PEOPLE
WITH HIV.
CRITICAL TO ACCOMPLISHING THE
OAR MISSION IS TO UNDERSTAND THE
PERSPECTIVES OF PEOPLE WITH HIV.
OAR LISTEN NG SESSIONS WITH
COMMUNITY PARTNERS PROVIDE DATA
WE USE TO ENSURE THAT THE NIH
HIV RESEARCH PROGRAM IS
FLEXIBLE, AND RESEARCH
PRIORITIES ARE RESPONSIVE TO
EMERGING CHALLENGES AND
NEEDS.
IN THE NEXT SLIDE, LISTENING
SESSION WITH FEDERAL, ACADEMIC
AND COMMUNITY PARTNERS CONTINUE
TO GUIDE OAR FOCUS ON SPECIFIC
AREAS OF INTEREST, TIED TO THE
NIH HIV RESEARCH COMMISSION, ANE
CURRENT PRIORITIES FOR HIV AND
HIV RELATED RESEARCH.
WE CALL THESE AREAS OF INTEREST
SIGNATURE PROGRAMS.
THESE ARE MULTIDISCIPLINARY,
SUPPORTED BY MULTIPLE NIH
INSTITUTES, CENTERS AND OFFICES,
AND INCLUDES SPECIFICALLY PEOPLE
AGING WITH HIV, HIV AND WOMEN'S
HEALTH, TECHNOLOGY ADVANCES FOR
HIV RESEARCH, AND SUPPORT FOR
EARLY CAREER INVESTIGATORS IN
HIV RESEARCH.
I'M GOING TO BRIEFLY EXPLAIN OR
DESCRIBE EACH OF THESE PROGRAMS
STARTING WITH HIV AND AGING IN
THE NEXT SLIDE.
40 YEARS INTO THE PANDEMIC,
PEOPLE WITH HIV CAN NOW ACHIEVE
A NEARLY NORMAL LIFESPAN BECAUSE
OF HIGHLY EFFECTIVE
ANTIRETROVIRAL THERAPIES.
ONE OF THE OUTCOMES OF THIS
SUCCESS IS THAT MORE THAN HALF
OF THE APPROXIMATELY 1.2 MILLION
PEOPLE WITH HIV IN THE UNITED
STATES ARE 50 YEARS OR OLDER.
THIS AGE GROUP HAS BEEN STEADILY
INCREASING AT ABOUT 5% PER YEAR
FOR THE LAST THREE YEARS.
VERSUS STABLE NUMBERS IN THE
YOUNGER AGE GROUPS.
IN 2020, IN ADDITION, ABOUT 17%
OF NEW INFECTIONS OCCURRED IN
PERSONS OLDER THAN AGE 50.
OLDER PEOPLE WITH HIV EXPERIENCE
AGE-RELATED COMPLICATIONS
INCLUDING NEUROCOGNITIVE
IMPAIRMENT, BONE AND MUSCLE
DISORDERS, AND CARDIOVASCULAR
DISEASE.
IN PARALLEL, PEOPLE AGING WITH
HIV FACE MULTIPLE SOCIAL AND
BEHAVIORAL CONCERNS, SUCH AS
INTERSECTIONAL STIGMA, SOCIAL
ISOLATION, AND MENTAL HEALTH
CONDITIONS.
OTHER SIGNIFICANT CHALLENGES IN
THIS POPULATION INCLUDE
POLYPHARMACY, INCREASED
CAREGIVER BURDEN AND COMPLEX
SUPPORT SERVICES.
IN THE NEXT SLIDE, A TOTAL OF 17
INSTITUTES, CENTERS AND OFFICES
SUPPORT THE MULTIFACETED HIV AND
AGING PORTFOLIO.
WITH ESTIMATED FUNDING FOR HIV
AND AGING RESEARCH IN FISCAL
YEAR 2022 OF ABOUT $119 MILLION.
THE NATIONAL INSTITUTE ON AGING,
NIA, CONTRIBUTES TO
APPROXIMATELY TAPPE 25% OF THIS
PORTFOLIO, NEARLY TRIPLE ITS
INVESTMENT SINCE 2017.
HEART, LUNG AND BLOOD, THE
OFFICE OF THE DIRECTOR, AND THE
NATIONAL INSTITUTES ON MENTAL
HEALTH ACCOUNT FOR ABOUT 40% OF
THE PORTFOLIO, WITH NIDA, NIAID,
NINDS, NIAA AND NCI AT ABOUT
25%.
WITH THE GROWING NUMBER OF
PEOPLE AGING WITH HIV, WE
ANTICIPATE THE NEED FOR GREATER
SUPPORT IN THE FUTURE.
SO THE HIV AND AGING SIGNATURE
PROGRAM AIMS TO CATALYZE
COLLABORATIONS TO ADDRESS
RESEARCH GAPS IN OPPORTUNITIES
AT THE INTERSECTION OF HIV AND
AGING.
OAR HAS PARTNERED WITH NIA TO
FORM THE NIH HIV WORKING GROUP.
THIS GROUP AIMS TO LINK
STRATEGIC PARTNERS ACROSS
GOVERNMENT AGENCIES, ACADEMIA
AND COMMUNITY ORGANIZATIONS TO
ENSURE THAT NIH RESEARCH IS
ALIGNED WITH COMMUNITY NEEDS AND
CULTURAL PREFERENCES.
IN THE NEXT SLIDE, A SECOND
SIGNATURE PROGRAM FOCUSED ON HIV
AND AGING.
GLOBALLY, WOMEN AND GIRLS
ACCOUNT FOR 49% OF ALL NEW
INFENGINFECTIONS IN 2021.
APPROXIMATELY 20 MILLION WOMEN
WORLDWIDE ARE HIV-POSITIVE,
WHICH IS ABOUT 54% OF THE GLOBAL
PREVALENCE.
IN SUB-SAHARAN AFRICA, YOUNG ADD
RE SENT GIRLS AND YOUNG WOMEN
ARE TWICE AS LIKELY TO HAVE HIV
THAN THEIR PEERS.
AMONG TRANSGENDER WOMEN, THERE'S
A 14 FOLD GREATER RISK OF
ACQUIRING HIV COMPARED TO
CISGENDER WOMEN, AND GLOBALLY,
THE PREVALENCE OF HIV AMONG
TRANSGENDER WOMEN IS
APPROXIMATELY 20%.
IN THE NEXT SLIDE, A
MULTIDISCIPLINARY APPROACH IS
CRUCIAL TO IMPROVE THE HEALTH OF
WOMEN WITH HIV, AND THIS
APPROACH IS REFLECTED IN THE NIH
HIV AND WOMEN'S HEALTH RESEARCH
PORTFOLIO.
THERE'S INVESTMENT BY 19 OF THE
27 INSTITUTES AND CENTERS IN A
WIDE RANGE OF RESEARCH TOPICS ON
HIV AND WOMEN, WITH ABOUT TWO
THIRDS OF THE PORTFOLIO FROM
NIAID AND NICHD.
BUT COLLABORATIONS ACROSS THE
ICs, THE OAR AND THE OFFICE OF
RESEARCH ON WOMEN'S HEALTH,
ORWH, FOR CROSS-CUTTING RESEARCH
AND THERAPIES FOR HIV-ASSOCIATED
COMORBIDITIES AND COINFORECASTS.
OAR'S SIGNATURE PROGRAM ON HIV
AND WOMEN IN PARTNERSHIP WITH
ORWH AIMS TO PROMOTE THE NIH
VISION FOR WOMEN'S HEALTH WHERE
ALL WOMEN, INCLUDING TRANSGENDER
WOMEN AND INDIVIDUALS ASSIGNED
FEMALE AT BIRTH RECEIVED
EVIDENCE-BASED,
GENDER-AFFIRMING, TAILORED HIV
PREVENTION, CARE AND TREATMENT.
THIS PROGRAM ALSO SUPPORTS WOMEN
IN SCIENCE CAREERS TO REACH
THEIR FULL POTENTIAL.
OAR AND THE OFFICE OF RESEARCH
ON WOMEN'S HEALTH RECENTLY
LAUNCHED AN NIH HIV AND WOMEN
WORKING GROUP TO IDENTIFY GAPS
AND PRIORITIES AT THE
INTERSECTION OF WOMEN'S HEALTH
AND HIV.
AND THERE WILL BE A JOINT
SYMPOSIUM AT THE 13TH
INTERNATIONAL WORKSHOP ON WOMEN
AND HIV THAT'S SCHEDULED TO
OCCUR JUST BEFORE -- NEXT MONTH
IN SEATTLE.
THIS WILL FOCUS ON ADOLESCENT
GIRLS AND YOUNG WOMEN,
MULTI-MORBIDITY AND AGING, AND
SOCIAL AND STRUCTURAL
CONSIDERATIONS IN HIV RESEARCH.
IN THE NEXT SLIDE IS A FOCUS ON
TECHNOLOGY FOR HIV RESEARCH,
WHICH PICKS UP ON SOME OF THE
THEMES THAT CARL INTRODUCED.
BUT BEFORE I DISCUSS THE TECH
KNOWLEDGE FOR HIV RESEARCH
SIGNATURE PROGRAM, I'D LIKE TO
MENTION THAT WHEN WE WERE AT THE
AIDS 2022 CONFERENCE IN MONTREAL
THIS PAST SUMMER, WE VISITED A
LOCAL HIV CLINIC.
THERE WE COULD SEE HOW PROVIDERS
LEVERAGE TECHNOLOGY TO ENABLE
CLIENTS TO SCHEDULE APPOINTMENTS
ONLINE, SELF-TEST ON SITE, AND
LEARN RESULTS VIA TELEHEALTH
APPOINTMENTS.
AND THESE INNOVATIONS ALONG WITH
STATUS NEUTRAL HIV AND STI
TESTING, PREVENTION AND
TREATMENT SERVICES ALL IN ONE
PLACE MAKE HIV CARE MORE
CONVENIENT AND ACCESSIBLE.
PROGRAMS LIKE THIS ARE CRITICAL
TO HIV EPIDEMIC CONTROL AND TO
THE PREVENTION OF NEW
INFECTIONS.
AND CURRENTLY, THERE ARE FEW
POINT OF CARE OPTIONS FOR VIRAL
LOAD MONITORING OR EVEN HIV
SELF-TESTING IN PART BECAUSE
COSTS ARE PROHIBITIVE.
THE TECHNOLOGY FOR HIV RESEARCH
SIGNATURE PROGRAM AIMS TO
ADVANCE RESEARCH TO DEVELOP
INNOVATIVE PRODUCTS SUCH AS
AFFORDABLE AT-HOME TESTS FOR
VIRAL LOAD MONITORING AND
INCREASED ACCESS TO
POINT-OF-CARE TESTING WITHIN
COMMUNITIES.
IN THE NEXT SLIDE, FOCUSING ON
EARLY CAREER INVESTIGATORS,
WHICH IS ANOTHER FREQUENT THEME
FROM LISTENING SESSIONS, AND AS
WE CAN SEE HERE IN THIS QUOTE
FROM THE FIRST OAR HIV
STAKEHOLDER ENGAGEMENT REPORT
FROM 2020.
AND I'LL JUST GIVE YOU A MINUTE
TO READ THAT YOURSELF.
IN THE NEXT SLIDE, THE FEEDBACK
THAT WE'VE BEEN HEARING FROM
LISTENING SESSIONS LED OAR TO
ANALYZE AND REVIEW SUPPORT FOR
NEXT GENERATION RESEARCHERS IN
THE HIV PORTFOLIO OVER TIME.
THE FOCUS DEVELOPED FROM AN
NIHIN' WIDE INITIATIVE TO
INCREASE THE NUMBER OF NEXT
GENERATION RESEARCHERS RECEIVING
R01 EQUIVALENTS ACROSS THE NIH
IN GENERAL.
THE GRAPH SHOWS THAT THE NUMBER
OF EARLY CAREER INVESTIGATORS IN
HIV RESEARCH, IN RED, HAS
INCREASED, BUT TO A LESSER
EXTENT AN OVERALL NIH EARLY
STAGE INVESTIGATORS IN BLUE.
OAR HAS DEVELOPED A SIGNATURE
PROGRAM THAT AIMS TO INCREASE
THE NUMBER OF EARLY STAGE
INVESTIGATORS IN HIV AND STABLY
SUPPORT THE NEXT GENERATION OF
THE HIV RESEARCH WORKFORCE.
A SUSTAINED DIVERSE HIV RESEARCH
WORKFORCE IS ESSENTIAL TO
CONTINUE MOMENTUM TO END THE HIV
EPIDEMIC.
OAR HAS PARTNERED WITH MULTIPLE
ICOs TO PROVIDE CAREER
DEVELOPMENT RESOURCES AND
OPPORTUNITIES INCLUDING AN EARLY
CAREER INVESTIGATOR RESOURCE
PAGE ON THE OAR WEBSITE.
IN 2022, OAR LAUNCHED THE
INAUGURAL VIRTUAL EARLY CAREER
INVESTIGATOR WORKSHOP, AND AT
THIS TIME, I'D LIKE TO THANK
NIAID AND ALL THE ICs FOR
SUPPORTING THE SECOND 2023
WORKSHOP FOR EARLY CAREER
INVESTIGATORS IN HIV SCHEDULED
FOR APRIL 24TH.
IN THE NEXT SLIDE.
FOR 35 YEARS, OAR HAS
COORDINATED THE PROGRAM
CONVENING MULTIPLE PARTNERS TO
CATALYZE INTERDISCIPLINARY
EFFORTS.
SO WHAT'S NEXT?
OUR GOAL REMAINS THE SAME.
END THE HIV PANDEMIC AND IMPROVE
THE HEALTH OF PEOPLE WITH HIV.
AND TO ACCOMPLISH THIS GOAL, WE
MUST FOCUS ON ACTION TO PREVENT,
TO TREAT, AND TO CURE.
THESE ACTIONS WILL REQUIRE
CONTINUED COMMITMENT, INNOVATION
AND CREATIVITY.
TO REDUCE ANY EFFORTS NOW WOULD
LEAD TO THE RESURGENCE OF HIV
WORLDWIDE, COMPROMISING GLOBAL
HEALTH IN THE 21ST CENTURY.
WE MUST BE NIMBLE TO RESPOND TO
NEW CHALLENGES, LEVERAGE NEW AND
EXISTING PARTNERSHIPS, ENSURE
THAT ALL VOICES CAN CONTRIBUTE
AND THERE IS ROOM FOR ALL AT THE
TABLE.
WE MUST BUILD ON OUR ROBUST
REPERTOIRE OF OPTIONS THAT CAN
IMPROVE PREVENTION AND TREATMENT
STRATEGIES.
MEANWHILE, THE SCIENTIFIC AGENDA
WILL CONTINUE TO SUPPORT
MULTIDISCIPLINARY INNOVATIVE
RESEARCH IN I IMMUNOLOGY,
VIROLOGY, THE BEHAVIORAL AND
SOCIAL SCIENCES, AS WELL AS
IMPLEMENTATION RESEARCH WHICH IS
KEY FOR DISCOVERY TO THE
COMMUNITIES WHO WOULD BENEFIT
THE MOST.
AS WE HEARD FROM DR. TONY FAUCI
AT OAR'S NIH WORLD AIDS DAY
EVENT LAST MONTH, ENDING THE
PANDEMIC, THE HIV PANDEMIC, IS
AN AMBITIOUS BUT FEASIBLE GOAL
AT NIAID, ONE THAT WE CAN
ACHIEVE.
THANK YOU.
>>THANK YOU, DR. GOODENOW, FOR
REALLY IMPRESSIVELY FOCUSED
INITIATIVES AND THOUGHTS AND
PARTICULARLY EXCITING TO SEE THE
BREADTH OF EFFORT ACROSS ALL OF
THE INSTITUTES, CENTERS AND
OFFICES, EVEN AS WE ARE SPEAKING
WITHIN THE DIVISION OF AIDS AT
NIAID, HOW BROAD THOSE EFFORTS
ARE.
MAYBE WE'LL TAKE TIME FOR A
COUPLE OF QUESTIONS.
DR. FRANK?
>>THANKS, KEN.
DR. GOODENOW, THIS IS IAN FRANK
FROM THE UNIVERSITY OF
PENNSYLVANIA.
ABOUT A WEEK 1/2 AGO IN
PREPARATION FOR THIS CALL TODAY,
WE HAD A PRELIMINARY CALL WITH
CARL, AND HE SHARED SOME
INFORMATION ABOUT THE NUMBER OF
K AWARDS THAT HAD BEEN FUNDED
THROUGH NIAID THE FACT
THAT IT WAS A NUMBER THAT WAS
SMALLER THAN IT HAD BEEN IN
RECENT YEARS.
I THINK THE NUMBER WAS FIVE, IF
I REMEMBER THAT NUMBER
CORRECTLY.
SO I'M WONDERING HOW MANY EARLY
STAGE CAREER INVESTIGATOR AWARDS
HAVE BEEN FUNDED THROUGH ALL OF
THE INSTITUTES, AND IS THAT
NUMBER ALSO IN THE DECLINE?
ARE THERE ANY INSTITUTES WHERE
THE NUMBER OF APPLICATIONS HAS
INCREASED?
>>THE OVERALL NUMBER FOR HIV
ARE NEW INVESTIGATORS RECEIVING
R01 OR R01 EQUIVALENTS IS IN THE
RANGE OF ABOUT 60 CURRENTLY AT
THE NIH.
AND THAT COMPARES, IF YOU USE
R01 EQUIVALENTS AS YOUR
DENOMINATOR, THEN AT THE TOTAL
NIH LEVEL, THE PERCENT OF AWARDS
OVERALL THAT ARE GOING TO NEW
INVESTIGATORS ACROSS THE NIH IS
ABOUT 5%.
WITHIN THE HIV AREA, IT'S A
LITTLE UNDER 4%.
SO ON A PERCENT-WISE BASIS,
WE'RE NOT AT THE SAME
PROPORTIONAL LEVEL AS THE REST
OF THE NIH.
>>K AWARDS.
WHAT ABOUT K AWARDS?
>>K AWARDS ARE IN A DIFFERENT
CLASS, AND I DON'T HAVE THOSE
NUMBERS AT THE TOP OF MY HEAD
RIGHT AT THIS MOMENT, BUT WE CAN
GET YOU THAT INFORMATION.
BUT IN GENERAL, THE IC -- IT
DEPENDS ON THE IC, WHICH ONES
ARE FUNDING MORE OR LESS,
BECAUSE THIS IS DEFINITELY
WITHIN THE IC PARAMETERS, WE CAN
PROVIDE THE DATA AND ENCOURAGE
THEM TO INCREASE THAT, AND WE,
IN FACT, HAVE BEEN USING OUR
RESOURCES TO SORT OF JUMP-START
SOME NEW FUNDING IN THIS AREA.
>>THANKS.
>>CERTAINLY THE RED LINE THAT
YOU SHOWED ON THAT GRAPH WITH
THE ESIs IN HIV GOING DOWN
WHILE EVERYONE ELSE WAS GOING UP
WAS NOT SOMETHING THAT ANY OF US
LIKE TO SEE.
SO WE'LL PUT OUR HEADS TOGETHER
AND THINK ABOUT WHAT WE CAN DO.
THANK YOU, DR. GOODENOW.
WHY DON'T WE MOVE ON AS WE MOVE
TO THE PROGRAMMATIC OVERVIEW,
AND LET ME REMIND EVERYONE TO
THINK ABOUT QUESTIONS
PARTICULARLY AROUND THE COVID
RESPONSE THAT WE'LL HAVE TIME
FOR IN THE DISCUSSION AT THE
END.
I'M GOING TO TURN IT OVER TO
DIANA FINZI, DIRECTOR OF THE
BASIC SCIENCES PROGRAM, FOR THE
NEXT PIECE OF THIS.
DR. FINZI.
>>YES, HELLO, EVERYONE.
AND JUST GIVE ME ONE MINUTE TO
SHARE MY SCREEN.
AND TO MOVE YOU OUT OF MY WAY.
OKAY.
SO GOOD AFTERNOON, EVERYONE.
I WILL START WITH AN OVERVIEW OF
THE BASIC SCIENCES PROGRAM, AND
THEN I'LL GIVE YOU SOME
HIGHLIGHTS FROM THREE IMPORTANT
AREAS FOR -- FOR MY PROGRAM IN
STRUCTURAL BIOLOGY, HIV CURE,
AND ENDING THE HIV EPIDEMIC.
I WILL TOUCH ON LESSONS LEARNED
WITH COVID THROUGHOUT THE TALK
AND WILL ALSO INCORPORATE
LESSONS LEARNED WHEN I DISCUSS
FUTURE DIRECTIONS.
A RECURRING THEME FROM MY GROUP
IS THAT OF LEVERAGING RESOURCES,
AND COLLABORATING AT EVERY
POSSIBLE OPPORTUNITY.
SO NOW I PROMISE I DID NOT
COORDINATE WITH KEN ON THIS, BUT
WE HAD VERY SIMILAR WORDS, WHICH
IS IF YOU THINK ABOUT IT, DEPTH
OF KNOWLEDGE GENERATED BY HIV
RESEARCH OVER THE PAST 40 YEARS
IS UNSURPASSED BY THE STUDY OF
ANY OTHER PATHOGEN.
NOT ONLY HAVE WE MADE ENORMOUS
STRIDES IN UNDERSTANDING HIV,
BUT WE'VE ALSO GAINED KEY
INSIGHTS ON OTHER VIRUSES.
FOR EXAMPLE, HIV LAID THE
FOUNDATION FOR UNDERSTANDING
ENTRY OF SARS-COV-2, AS WELL AS
THE MRNA TECHNOLOGY FOR THE
VACCINES.
AND THROUGH HIV, WE HAVE LEARNED
ABOUT THE COMPLEXITIES OF THE
IMMUNE SYSTEM, WE HAVE LEARNED
ABOUT HOW T-CELLS, B-CELLS AND
K-CELLS, MACROPHAGES,
ORCHESTRATE AN ATTACK AND HOW
SPECIFICALLY MOLECULES RECOGNIZE
AND BIND TO STRUCTURES, TO
PATHOGENIC STRUCTURES AND HOW
THEY WORK TOGETHER TO TARGET AND
CLEAR VIRUSES.
THIS LARGE BODY OF WORK HAS
CONTRIBUTED TO CRITICAL DISCOVEY
STRONG FOUNDATION TO ADDRESS
OTHER DISEASES AS DIVERSE AS
CURING CANCER.
MOST OF WHAT WE DO IS PROVIDE
EARLY STAGE SCIENCE.
THE EARLY INDICATIONS OF WHAT
MIGHT EVENTUALLY LEAD TO
IMPORTANT BREAKTHROUGHS.
OUR FOUNDATIONS ARE IN A LARGE
NUMBER OF UNSOLICITED GRANTS,
BUT WE ALSO SOLICIT GRANTS IN
ORDER TO INDICATE OUR DIRECTION
IN AREAS OF PARTICULAR NEED.
WE WORK WITH OTHER PROGRAMS, WE
WORK WITH THERAPEUTICS
PREVENTION AND VACCINES, AND
OFTEN SEE OUR EARLY WORK BEAR
FRUIT IN THOSE AREAS.
AND WITH OUR BREADTH AND
RESOURCES SUCH AS THE CENTERS
FOR AIDS RESEARCH, WE'RE OFTEN
ABLE TO PLANT LITTLE SEEDS TO
GENERATE NEW IDEAS, SUPPORTING A
WIDE BASE FOR EXPLORATION AND
FEEDING THE PIPELINE WITH DEPTH
AND DIVERSITY OF PROJECTS.
SO I HOPE TO GIVE YOU A FEEL FOR
THE GREAT BREAD OF THE BREADTH O
IN BSP.
BSP IS CAN COMPOSED OF THREE
BRANCHES.
JASON AND ANNE ACT AS MY
DEPUTIES, AND BRITTANY THOMPSON
IS OUR EXTRAMURAL SUPPORT
ASSISTANT.
THE PATHOGENESIS AND BASIC
RESEARCH BRANCH IS LED BY CARL,
THE TARGETED INTERVENTIONS
BRANCH BY SANDRA BRIDGES GURGO,
AND THE EPIDEMIOLOGY BRANCH BY C
ARC RLIE WILLIAMS.
COLLECTIVELY, BSP OVERSEES OVER
550 GRANTS WITH AN ANNUAL BUDGET
OF OVER $400 MILLION.
WE ALSO OVERSEE SEVERAL
CONTRACTS THAT FOR THE MOST PART
PROVIDE SERVICES FOR THE FIELD,
SUCH AS THE AIDS REAGENT
PROGRAM.
SO OUR PRIMARY FOCUS IN THE
BRANCHES, IN THE PATHOGENESIS IN
BASIC RESEARCH BRANCH IS ON
MECHANISTIC WORK WITH PARTICULAR
ATTENTION TO LATENCY,
PERSISTENCE AND CURE.
AND OUR TARGETED INTERVENTIONS
BRANCH, WE HAVE AN INCREASED
FOCUS ON NON-TRADITIONAL
THERAPEUTICS, SUCH AS GENE AND
CELL-BASED THERAPIES, BIOLOGICS,
AND RNA THERAPEUTICS, BUT WE
ALSO CONTINUE WORK ON SPECIFIC
INTERVENTIONS TO VALIDATE HIV
TARGETS AND SMALL MOLECULE
INHIBITORS.
IN THE EPIDEMIOLOGY BRANCH, OUR
WORK FOCUSES ON CLINICAL
OUTCOMES OF HIV THROUGH VERY
LARGE COHORTS THROUGHOUT THE
WORLD, AND ON ELECTRONIC HEALTH
RECORDS RESEARCH.
RECENTLY FOCUSING MORE ON
TUBERCULOSIS AND THE
INTERSECTION OF TB AND HIV.
THE EPIDEMIOLOGY BRANCH HAS ALSO
EXPANDED SUPPORT OF NEW
SURVEILLANCE APPROACHES TO
IDENTIFY PEOPLE WHO ARE AT RISK
OF INFECTION AND PEOPLE WHO ARE
AT RISK OF INADEQUATE TREATMENT.
AND NOW THREE YEARS INTO THE
FEDERAL ENDING THE HIV EPIDEMIC,
WHERE OUR CFAR TEAM ALONG WITH
OUR NATIONAL INSTITUTE OF MENTAL
HEALTH COLLEAGUES HAVE TAKEN THE
LEAD FOR THE NIH AND ESTABLISHED
A PARTNERSHIP WITH THE OFFICE OF
AIDS RESEARCH, THE CDC, AND HRSA
TO ACHIEVE EAG GOALS.
OUR EFFORTS HAVE RESULTED IN
INCREASED EFFORT AND ALIGNMENT
TO FUND HIV IMPLEMENTATION
SCIENCE RESEARCH.
SO YOU CAN ALREADY SEE FROM HERE
THAT THE BREADTH OF WHAT WE DO
IN BSP IS REALLY QUITE GREAT.
IT RANGES FROM BASIC SCIENCE AT
THE SUBCELLULAR ATOMIC LEVEL TO
UNDERSTANDING THE BIOLOGY AND
THE IMMUNOLOGY OF HIV, TO
EPIDEMIOLOGY AND THE DYNAMICS OF
HIV TRANSMISSION BETWEEN PEOPLE.
SO NOW I'M GOING TO START SMALL
WITH A VERY EXCITING STORY FROM
OUR STRUCTURAL BIOLOGY CENTERS.
SO JUST ABOUT 20 YEARS AGO, WE
STARTED A CLOSE COLLABORATION
WITH NIGMS WHERE TOGETHER WE
LAUNCHED THREE CENTERS FOR HIV
STRUCTURAL BIOLOGY, FUNDED
MOSTLY BY NIGMS.
AND THEN A FEW YEARS AGO IN
2019, WE TOOK OVER THE ENTIRE
HIV STRUCTURAL BIOLOGY PORTFOLIO
FROM NIGMS AND EXPANDED THE
PROGRAM AND WE NOW HAVE SIX
CENTERS.
SO MY FIRST SCIENTIFIC HIGHLIGHT
IS ABOUT A NEW DRUG THAT HAS
BEEN DEVELOPED CALLED
LENOCAPIVIR AND IT'S BASED ON
FUNDAMENTAL SCIENCE DONE BY WEST
SUNDQUIST AT THE CHEETAH CENTER
LISTED HERE AND ALSO FROM
INVESTIGATORS IN THE FOUR OTHER
CENTERS THAT ARE HIGHLIGHTED IN
RED.
AND AS I MENTIONED BEFORE, I
THINK TO THIS GROUP, ONE OF THE
HARDEST PARTS WITH BASIC SCIENCE
IS THAT THE PAYOFF CAN TAKE
MANY, MANY YEARS TO EMERGE, AND
PEOPLE OFTEN PREFER SEEING
IMMEDIATE RESULTS.
THE COMMENT "PRETTY PICTURES BUT
WHAT WILL DO FOR ME" IS PRETTY
TYPICAL.
IT'S REALLY HARD TO GENERATE
EXCITEMENT FOR WORK THAT ISN'T
IMMEDIATELY TRANSLATABLE.
SO NOW I'LL SHOW YOU SOME PRETTY
PICTURES, AND HOPEFULLY WE'LL
GIVE YOU AN IDEA OF THE
IMPORTANCE OF INVESTING IN BASIC
SCIENCE.
AN EXAMPLE OF THAT.
SO WE'RE ALL FAMILIAR WITH THE
HIV LI LIFECYCLE.
THIS NEW DRUG ACTS ON PROTEINS
THAT MAKE UP THIS CONICAL
STRUCTURE CALLED THE CORE.
THE CORE IS ESSENTIAL DURING
ENTRY OF THE VIRUS AS IT
PROTECTS THE HIV'S GENETIC
INFORMATION FROM INNATE IMMUNE
SENSORS DURING REVERSE
TRANSCRIPTION, AND ALSO WHILE IT
TRAFFICS THROUGH THE CYTOPLASM
TO THE NUCLEUS.
THE CORE THEN FALLS APART -- OR
UNCOATS, AS GENETIC INFORMATION
IS RELEASED AND TRANSPORTED INTO
THE NUCLEUS FOR INTEGRATION.
ON THE RIGHT-HAND SIDE, CORE
ASSEMBLY IS ALSO VERY IMPORTANT,
AS THE VIRUS BUDS FROM THE CELL
AND CRITICAL TO THE LIFECYCLE,
AS WELL AS THE MATURING OF
CAPSID.
THE PROTEINS THAT MAKE UP THIS
CORE ARE CALLED CAPSID.
NOW EARLY WORK IN THE MID
1990s BY WES SUNDQUIST, MIKE
SOMERS AND CHRIS HILL'S GROUP
SHOWED THE BASIC STRUCTURE OF
THE CAPSID PROTEIN DIMER AND
FOUND THAT 750 OF THESE DIMERS
MUST COME TOGETHER TO FORM THE
CONE, BUT EXACTLY HOW THESE
DIMERS CAME TOGETHER TO FORM
THIS HIGHER SCALE CONICAL BUT
SLIGHTLY IRREGULAR STRUCTURE
REMAINED UNKNOWN.
ABOUT 10 YEARS LATER, WE BEGAN
TO HAVE CLARITY AROUND THIS
QUESTION.
THIS SLIDE SHOWS THE CAPSID
DIMER ON THE LEFT, AND THEN THE
ATOMIC STRUCTURES OF CAPSID
PENTAMERS AND HEXAMERS MADE OF .
THESE PENTAMERS AND HEXAMERS ARE
THE ESSENTIAL BUILDING BLOCKS,
AND THESE IMAGES REPRESENT THE
FIRST ATOMIC MODELS FOR THE HIV
CAPSID BUILDING BLOCKS.
AND THESE IMAGES ALSO STARTED TO
GIVE IMPORTANT HINTS TO ENABLING
STRUCTURE-BASED DESIGN.
NOW HERE, THIS IS THE FULL
STRUCTURE OF THE CORE.
THE FULERINE CONE, WHICH IS
COMPOSED OF 250 HEXAMERS, WHICH
ARE HERE IN ORANGE, AND 12
PENTAMERS IN YELLOW.
THIS WORK DEFINED THE FULL
ARCHITECTURE OF THE CAPSID OR
THE CORE STRUCTURE.
NOTE THAT THE RINGS ARE COMPOSED
OF AND HELD TOGETHER BY THE
CAPSID-DIMER INTERACTION.
NOW BASED ON THESE FINE DETAILS
OF THESE ANTIACTIONS, GILEAD
DEVELOPED AN ASSAY THAT SHOWED
HOW THE KINETICS OF CAPSID
ASSEMBLY WERE EITHER INHIBITED
OR ACTUALLY ACCELERATED WITH THE
ADDITION OF SMALL MOLECULE DRUG
CANDIDATES.
THEY THEN USED STRUCTURE-BASED
DESIGN TO DRIVE THE MEDICINAL
CHEMISTRY.
SO NOTE HERE ON THE LEFT THE
HIGH COMPLEXITY OF THIS
MOLECULE.
WHICH INCLUDES TWO STEREO
CENTERS, MULTIPLE DIFFERENT
TYPES OF ATOMS.
WES SUNDQUIST REFERS TO THIS AS
A HEROIC EFFORT BY GILEAD.
THE IMAGE ON THE RIGHT
HIGHLIGHTS THE FACT THAT THE
DRUG BINDS TO A POCKET IN THE
MIDDLE OF THE CAPSID DIMER, AND
SHOWS THAT ALL THE KNOWN SITES
OF DRUG RESISTANCE MAP TO THE
SITE, PROVING THAT THE CAPSID IS
THE THERAPEUTIC TARGET FOR THIS
DRUG.
IT'S IMPORTANT TO POINT OUT THAT
THE DRUG WAS DEVELOPED AT
GILEAD.
WES SUNDQUIST HELPED ESTABLISH
THE FOUNDATIONAL STRUCTURAL
BIOLOGY, AND HE HELPED SET UP
THE ASSAYS, BUT ALL OF THE DRUG
DEVELOPMENT, TESTING, ALL OF IT
WAS DONE BY GILEAD.
SO THIS IS REALLY AN EXAMPLE OF
EYE DEAN COLLABORATION BETWEEN
THE GOVERNMENT, ACADEMIA AND
INDUSTRY.
NOW I WANT TO SHOW HERE THE
POTENCY, IT'S A MORE POTENT
INHIBITOR THAN ANY OF THE COMMON
DRUGS USED IN THE CLINIC,
INCLUDING TAFF -- AND THEN THIS
NEXT SLIDE HERE SHOWS THAT AT
HIGHER DOSES, THE DARKER BLUE
LINES, LENACAPAVIR LASTS AT
THERAPEUTIC LEVEL FOR QUITE A
LONG TIME, SIX MONTHS, FOLLOWING
A SINGLE SUBCUTANEOUS DOSE.
SO THE KEY POINTS FOR THIS
LENACAPAVIR IS THAT IT IS A
FIRST IN CLASS CAPSID INHIBITOR,
IT BLOCKS MULTIPLE
CAPSID-DEPENDENT STEPS IN HIV
REPLICATION INCLUDING NUCLEAR
ENTRY -- IT HAS A GREAT PROFILE
AGAINST KNOWN RESISTANCE
MUTATIONS BECAUSE IT HITS A NEW
TARGET, AND IT NOW HAS BEEN
APPROVED FOR USE IN EUROPE AND
THE UNITED STATES IN ADULTS WHO
HAVE RESISTANT VIRUS.
WHILE IT'S GREAT AND VERY
IMPORTANT TO HAVE A NEW DRUG
THAT HELPS PATIENTS, THERE'S
REALLY GREAT EXCITEMENT IN HOW
THIS CAN DRIVE FURTHER PROGRESS
IN IMPROVING HIV TREATMENT
OVERALL.
FIRST, THE LONG LASTING
PHARMACOKINETICS OF THE DRUG
ALLOW FOR SIX HAD BEEN MONTH SID
THAT WILL FACILITATE ADHERENCE
AND VIRAL SUPPRESSION IN
PATIENTS WHO HAVE A HARD TIME OR
DIFFICULTY ADHERING TO DAILY
REGIMENS, AS WELL AS FOR
PEDIATRIC PATIENTS AND YOUNG
ADULTS.
AND PERHAPS JUST AS EXCITINGLY,
IT HAS REALLY AWESOME POTENTIAL
IN PREP APPLICATIONS.
YOU CAN ENVISION THAT ITS
LONGEVITY WOULD ALLOW TO HAVE
ALMOST LIKE A VACCINE TO PREVENT
TRANSCRIPTION, EVEN IN AREAS AND
IN POPULATIONS WHERE THERE ARE
HIGH RATES OF RESISTANCE TO ORAL
REGIMENS.
THIS IS DEFINITELY A STORY TO
FOLLOW.
THE IDEA OF A SUBCUTANEOUS
INJECTION TWICE A YEAR AS EITHER
TREATMENT OR FOR PREVENTION
COULD REALLY BE -- HAVE AN
IMPORTANT IMPACT.
OKAY.
SO NOW THE NEXT AREA THAT I'D
LIKE TO TOUCH ON IS HIV CURE.
THIS IS AN AREA WHERE WE HAVE
FOSTERED COLLABORATIONS ON MANY
LEVELS, INCLUDING WITH THE IAS
AND WITH THE BILL AND MELINDA
GATES FOUNDATION, AS WELL AS
AMONG OUR GRANTEES.
THE MARTIN DELANEY
COLLABORATORIES REPRESENT OUR
FLAGSHIP PROGRAM.
WE NOW HAVE 10 MARTIN DELANEY
COLLABORATORIES UP AND RUNNING,
WITH NEW BLOOD AND GREAT ENERGY.
AND I WILL FOCUS NOW FOR JUST A
MOMENT ON WORK THAT HAS COME OUT
OF THE DARE COLLABORATORY.
SO AS WE ALL KNOW, HIV HIDES IN
THE HUMAN GENOME.
IT'S LIKE A NEEDLE IN A
HAYSTACK.
CELLS THAT ARE LATENTLY AFFECTED
WITH HIV HAVE TWO
CHARACTERISTICS THAT MAKE THEM
INCREDIBLY DIFFICULT TO STUDY.
ONE, THEY HAVE NO DISTINGUISHING
MARKERS ON THEIR SURFACE, AND
TWO, THEY'RE VERY, VERY RARE.
AMONG MEMORY CELLS, AS SHOWN
HERE, THESE ARE A THOUSAND CELLS
ON THIS SCREEN, ABOUT 1 IN A
THOUSAND HAVE SOME INTEGRATED
HIV DNA.
A THOUSAND TIMES RARER, ABOUT
1 IN A MILLION, HAVE ACTUALLY
REPLICATION-COMPETENT PRO VIRUS.
SO THIS MAKES IT ESSENTIALLY
IMPOSSIBLE TO SEPARATE CELLS
WITH LATENT HIV FROM THEIR
UNINFECTED COUNTERPARTS, AND
THIS IS A PROBLEM THAT HAS
PLAGUED THE FIELD SINCE WHEN I
WAS IN THE LAB WORKING ON THIS
30 YEARS AGO.
BUT WE ARE CAREFULLY AND
METHODOLOGICALLY REALLY HONING
IN ON CHARACTERISTICS AND
BEHAVIORS OF LATENTLY INFECTED
CELLS, AND SOME OF YOU WILL
RECALL THAT LAST YEAR I TALKED
ABOUT CLONAL PROLIFERATION OF
THESE CELLS.
AND NOW HERE I WILL DESCRIBE A
NEW TECHNOLOGY FROM A VERY
RECENTLY PUBLISHED PAPER THAT
DIRECTLY ADDRESSES THIS PROBLEM
USING FOCUSED INTERROGATION OF
CELLS BY NUCLEIC ACID DETECTION
AND SEQUENCING, FIND-SEQ.
THIS IS A COMPLICATED SLIDE BUT
IF YOU FOLLOW ME THROUGH IT ON A
SUPERFICIAL LEVEL FROM LEFT TO
RIGHT, IT'S ESSENTIALLY
TECHNOLOGY THAT USES FOUR STEPS
TO ANALYZE GENETIC INFORMATION
FROM INDIVIDUAL CELLS.
FROM FAR LEFT, FIRST CELLS ARE
FUNNELED INTO A MICRO FLUIDIC
DEVICE, LOADS AND LEISTS
INDIVIDUAL CELLS AND RETAINS THE
GENETIC MATERIAL IN INDIVIDUAL
DROPLETS.
NEXT, PCR IS USED TO AMPLIFY
GENES THAT ARE EXPRESSED.
THE THIRD STEP, HIV DNA, IS
LABELED AND IN THE FOURTH, A
LASER IS USED TO SORT
FLUORESCENT DROPLETS THAT HAVE
HIV DNA FROM ONES THAT DON'T.
ONCE SORTED, THE DROPLETS CAN BE
ANALYZED FOR GENE EXPRESSION
PATTERNS.
USING THIS TECHNOLOGY, WE ARE
CATCHING THE VERY FIRST GLIMPSES
OF SIGNATURES OF LATENCY.
CLARKE ET AL. FOUND THAT HIV
INFECTED CELL TRANSCRIPTOMES
INCLUDED INHIBITION OF CELL
DEATH, INHIBITION OF
ANTIPROLIFERATIVE SIGNALING, AND
SIGNATURES OF HIV SILENCING.
NOW, THEY DEVELOPED THIS
TECHNOLOGY SPECIFICALLY FOR HIV,
BUT REALLY INTERESTINGLY, THEY
WERE ABLE TO APPLY THIS
TECHNOLOGY TO AN ENTIRELY
DIFFERENT DISEASE.
HERE THEY USE THE TECHNOLOGY TO
MAKE AN IMPORTANT DISCOVERY ON
MULTIPLE SCLEROSIS, WHERE THEY
HAVE IDENTIFIED A NEW ROLE FOR
GENE INVOLVED IN PATHOGENIC
ASTROCYTE RESPONSES, REVEALING A
THERAPEUTICALLY TARGETABLE
MECHANISM TO TREAT PEOPLE WHO
HAVE MULTIPLE SCLEROSIS.
OKAY.
SO NOW SHIFTING TO ENDING THE
HIV EPIDEMIC, OUR CENTERS FOR
AIDS RESEARCH AND ON THE HUMAN
SCALE OF RESEARCH, IN FEBRUARY
OF 2019, THE WHITE HOUSE
ANNOUNCED AN INITIATIVE TO END
THE HIV EPIDEMIC.
DR. FAUCI WAS, OF COURSE, BEHIND
THIS, AND THE SCIENCE ARTICLE BY
JOHN COHEN NICELY EXPLAINS HOW
DR. FAUCI GOT US INVOLVED.
HE STATED THAT THE CFARs,
MAINLY BASED AT UNIVERSITIES,
CONDUCT MULTIDISCIPLINARY
STUDIES INCLUDING ON HOW BEST TO
KEEP HIV INFECTED PEOPLE IN CARE
AND HELP UNINFECTED PEOPLE
ACCESS PROVEN INTERVENTIONS.
THE LOCATION OF THE 19 CFARs
BEAUTIFULLY OVERLAP, ALTHOUGH
NOT COMPLETELY, WITH THE HOT
SPOTS.
HE ALSO EMPHASIZED THAT THE
CFARs HAVE STRONG TIES TO
THEIR COMMUNITIES, AND THEY CAN
BETTER COORDINATE HOW THEY WORK
TOGETHER TO PREVENT NEW
INFECTIONS.
SO THEN JUMPING IN IMMEDIATELY
IN 2019 IN COLLABORATION WITH
OUR COLLEAGUES AT THE NATIONAL
INSTITUTE OF MENTAL HEALTH, WE
CHOSE TOPICS FOR OUR CFARs AND
AIDS RESEARCH CENTERS THAT COULD
HELP US ALIGN, COLLABORATE, AND
GUIDE THE CDC AND HRSA EFFORTS
WITH IMPLEMENTATION SCIENCE
STUDIES TOWARDS TREATMENT AND
PREVENTION OF HIV INFECTION.
THIS TABLE SUMMARIZES THE LARGE
NUMBER OF PROJECTS AND THE
GENERAL FOCUS FOR EACH OF THESE
AREAS.
AND NEXT HERE IS -- THIS SPECIAL
ISSUE REPORTED FINDINGS FROM THE
EHE SUPPLEMENT PROJECTS AS WELL
AS LARGER DOMESTIC RESEARCH
STUDIES FUNDED BY THE NIH.
THE ARTICLES INCLUDED HERE COVER
ALL GEOGRAPHIC REGIONS IN THE
UNITED STATES, INCLUDING URBAN
AS WELL AS RURAL LOCATIONS, AND
FOCUS ON PRIORITY POPULATIONS,
INCLUDING SEXUAL MINORITY MEN,
TRANSGENDER PEOPLE, AND BLACK
AND LATINA CISGENDER WOMEN.
SO SPEAKING OF WOMEN, SEVERAL
YEARS AGO, WE HAD A DISCUSSION
HERE IN THIS MEETING WHEN WE
WERE STILL ALL TOGETHER IN THE
SAME ROOM ABOUT THE DIFFICULTIES
OF STUDYING WOMEN WHO ARE AT
RISK OF BECOMING INFECTED.
WE ARE EMBARKING ON THE LIGHT
STUDIES WHICH USE SOCIAL MEDIA
AND DATING APPS TO REACH MOSTLY
MEN WHO HAVE SEX WITH MEN.
SOMEONE HERE PRESSED US TO FOCUS
MORE ON WOMEN, AND WOMEN WHO
WERE AT RISK OF INFECTION.
SO THIS ANNOUNCEMENT CAME OUT IN
2021.
AND WE HAVE JUST RECENTLY BEEN
ABLE TO FUND THREE GROUPS THAT
COMBINE EPIDEMIOLOGIC METHODS,
DIGITAL TECHNOLOGY, AND DATA
SCIENCE APPROACHES TO BETTER
UNDERSTAND HIV PREVENTION,
TRANSMISSION, AND EARLY CARE
CASCADE POINTS FOR WOMEN LIVING
IN THE UNITED STATES.
ALL OF THESE PROJECTS ARE LED BY
WOMEN INVESTIGATORS, AND FOCUS
ON AT RISK WOMEN.
SO NOW JUST TO GIVE A LITTLE
PREVIEW OF THE WORK FROM ONE OF
THESE GROUPS, ANDREA WORTZ AND
COLLEAGUES WORKING WITH
TRANSGENDER WOMEN PRESENTED AT
AIDS 2022 IN MONTREAL.
WE ALL NO KNOW THAT TRANSGENDER
WOMEN ARE AT HIGHER RISK BUT
THEY HAVE ENROLLED THE FIRST
MULTISITE COHORT TO ESTIMATE HIV
INCIDENCE IN TRANSGENDER WOMEN
LIVING IN THE UNITED STATES.
THEIR PAPER IS UNDER EMBARGO SO
WE CAN'T DISCUSS THE DETAILS,
BUT THEY REPORT SIGNIFICANTLY
HIGHER RATES OF HIV INCIDENCE
AMONG BLACK PARTICIPANTS, AND
SIGNIFICANTLY HIGHER MORTALITY
RATES IN HISPANIC POPULATIONS.
THE PAPER WILL BE COMING OUT
SOON IN LANCET HIV, SO STAY
TUNED FOR THAT.
SO NOW WRAPPING UP AND COMING TO
FUTURE DIRECTIONS, AS I
MENTIONED EARLIER, THE DEPTH OF
KNOWLEDGE THAT WE HAVE GAINED
THROUGH HIV IS TREMENDOUS.
IN OUR BASIC SCIENCES AND
TARGETED INTERVENTIONS BRANCHES,
OUR INITIATIVES WILL FOCUS ON
FURTHER DEEPENING KNOWLEDGE AND
FOCUSING ON DETAILS OF THE PRO
VIRUS, THE VIRUS, AND HOW TO
TARGET IT VERY SPECIFICALLY BY
THE IMMUNE SYSTEM, WHERE EVEN
THE SMALLEST CHANGES CAN MAKE A
BIG DIFFERENCE IN WHAT IS
RECOGNIZED.
SO WE ARE LOOKING TO FURTHER
CLOSING IN ON OUR TARGET OF THE
HIV PRO VIRUS.
AS FAR AS LESSONS LEARNED WITH
COVID, WE HAVE LEARNED THAT
LEVERAGING WHAT WE HAVE LEARNED
THROUGH HIV HAS BEEN EXTREMELY
USEFUL SCIENTIFICALLY IN
COMBATING SARS FROM, AS I
MENTIONED EARLIER, DETERMINING
THE STRUCTURE OF SPIKE TO
DESIGNING MRNA VACCINES.
THE CHALLENGES HAVE MORE TO DO
WITHDRAWING FUNDING LINES, AS
CARL MENTIONED EARLIER.
EVERYBODY OF OUR GRANTEES WAS
VERY EAGER TO HELP SOLVE COVID,
BUT FUNDING LINES HAD TO BE
DRAWN.
SIMILARLY, IN EPIDEMIOLOGY AND
ENDING THE HIV EPIDEMIC, WE ALSO
AIMED TO GET A DEEPER
UNDERSTANDING OF WHAT IS
HAPPENING ON THE LEVEL OF THE
INDIVIDUAL, TRYING TO REACH
PEOPLE MORE DIRECTLY,
UNDERSTANDING INTERPERSONAL
DYNAMICS IN AT-RISK POPULATIONS
AND LEADING IMPLEMENTATION
SCIENCE STUDIES TO PROTECT OUR
PEOPLE USING EFFECTIVE
STRATEGIES.
IN TERMS OF LESSONS LEARNED, THE
DOMESTIC AND WORLDWIDE NETWORK
OF HIV RESEARCHERS CONTRIBUTED
IMMENSELY TO THE RABID RESPONSE
OF COVID.
IF WE CANNOT LEVERAGE OUR
RESOURCES, WE CAN CERTAINLY
CONTINUE TO LEVERAGE THROUGH
BASIC SCIENCE AND THROUGH ALL OF
OUR INTERPERSONAL COLLABORATIONS
AND CONNECTIONS DOMESTICALLY AND
ABROAD.
SO I WILL END BY THANKING ALL OF
MY COLLEAGUES IN BSP FOR THE
WORK THAT WE'VE BEEN DOING
TOGETHER, ESPECIALLY OVER THESE
PAST THREE YEARS, AND I ALSO
WANT TO THANK YOU ALL FOR YOUR
ATTENTION, AND I'M HAPPY TO
ANSWER ANY QUESTIONS.
AND I'LL TRY TO STOP SHARING.
>>THANK YOU, DR. FINZI.
YOU SHOWED SOME BEAUTIFUL
PICTURES AND SOME EVEN MORE
BEAUTIFUL SCIENCE, SO THAT WAS
REALLY FA FANTASTIC.
>>JUST ONE SECOND.
DID I CALL YOU DR. FRIEDMAN?
BECAUSE WE HAVE VERY CLOSE
FRIENDS.
>>WHATEVER.
>>I THINK I SAID FRIEDMAN
INSTEAD OF FREEDBERG.
BUT OF COURSE I KNOW YOU'RE YOU.
>>THAT'S FINE.
YES, I AM DEFINITELY ME.
ALTHOUGH I GO BY STANLEY TUCCI
ON OCCASION.
SO, QUESTIONS.
>>DIANA, I HAVE A QUESTION.
IT'S MAYBE NOT TOO SCIENTIFIC,
BUT THE LENACAPAVIR STORY IS
FANTASTIC, SUPER EXCITING,
WONDERFUL DRUG THAT'S GOING TO
COST $40,000 A PATIENT A YEAR IN
PROJECTED SALES OR $4 BILLION A
YEAR.
SO, YOU KNOW, YOU SAID THIS IS
THIS WONDERFUL COLLABORATION
BETWEEN THE GOVERNMENT, ACADEMIA
AND PHARMA.
OBVIOUSLY DRUG PRICES ARE
GETTING MORE AND MORE ATTENTION
AS THE YEARS ARE GOING ALONG.
I DON'T KNOW.
YOU KNOW, IS THAT EVEN A PART OF
WHAT YOU CONSIDER AS THESE
PROGRAMS MOVE AHEAD?
AS SORT OF
THE PUBLIC ADVOCATES FOR THE
AMERICAN TAXPAYER?
>>SO UNFORTUNATELY, OUR JOB IS
DISCOVERY, RIGHT?
AND THE BASICS, THE UNDERLYING
BASICS.
I AGREE WITH YOU THAT IT'S
HORRIBLE, BUT THAT REALLY IS --
AT LEAST IT'S NOT IN ANY WAY
ANYTHING I CAN DO ANYTHING
ABOUT.
AND PART --
>>LET ME MAKE A QUICK COMMENT,
THAT RIGHT NOW IF I GO DOWN TO
CVS AND BUY FIRST LINE HIV ORAL
THERAPY, PAY CASH, IT'S ABOUT
$48,000 A YEAR, TLD COSTS $42 A
YEAR, 4-2.
SO WHAT HAS HAPPENED
HISTORICALLY WITH HIV DRUGS, IN
NO OTHER AREA OF MEDICINE, I
THINK IT IS OUR COLLECTIVE
SOCIAL AND GLOBAL RESPONSIBILITY
TO MAKE SURE THAT EFFECTIVE NEW
DRUGS BECOME AVAILABLE.
SO LET'S TAKE THAT ON AS PART OF
OUR AGENDA.
MONICA HAS A QUESTION.
>>YES.
THAT WAS REALLY GREAT.
I THINK THAT LANGE LONG ACTING O
EXCITING, I CAN'T EVEN SIT
STILL.
LENACAPAVIR, A COUPLE QUESTIONS
ON SOME OF THE BASIC SCIENCE
WHICH IS THAT IT IS INTERESTING
IN THE PICTURE THAT YOU SHOW
THAT IN A WAY, IT'S THROUGHOUT
THE LIFECYCLE, IT NOT AT THE
VERY END, WHERE CAPSID
INHIBITION OCCURS.
AND I THINK THAT IS IS REALLY
HEARTENING IN THE SENSE THAT
INITIALLY IN THE ECTG, WE WERE
SAYING WE CAN'T EACH THINK ABOUT
THIS FOR CURE OR SUPPRESSION OF
VIREMIA BECAUSE EVERYTHING IS
GOING TO OCCUR AT THE END, BUT
TO A VIROLOGIST WHO REALLY
UNDERSTANDS WHERE LENACAPAVIR IS
WORKING, APPARENTLY THERE IS A
POSSIBILITY, AND THIS IS GOING
TO BE STUDIED IN THE ECTG OF
REDUCING EVEN LOW GRADE VIRAL
LOADS.
YOU KNOW, EVEN IN BETWEEN.
COULD IT BE REDUCING HIV DNA
LEVELS, COULD IT BE EVEN IN
BETWEEN.
AND I WOULD JUST COMMENT, YOU
KNOW, ON THE PRICE BECAUSE --
ONLY BECAUSE IF WE THOUGHT ABOUT
THE TDF/FTC TRIALS, AND I THINK
THIS IS DIFFERENT BUT I'M JUST
GOING TO ASK YOU THIS DIRECTLY,
THE REASON THAT THERE WAS
CONTROVERSY AROUND THE PRICE OF
THE ORIGINAL TDF/FTC FROM GILEAD
IS BECAUSE ALL THE CLINICAL
TRIALS FOR PREP WERE FUNDED BY
THE NIH.
SO IPREX, ALL OF THEM WERE
FUNDED NOT BY THE DRUG COMPANIES
BUT IT WAS REALLY GOVERNMENTAL
MONEY THAT FUNDED THE BIG
CLINICAL TRIALS.
LENACAPAVIR, THE CAPELLA STUDY
IS THE ONLY MAJOR ONE, THERE'S
ALSO CALABRE AND I THINK IT WAS
FUNDED BY THE DRUG COMPANY.
IS THAT CORRECT?
NOT BY -- NOT BY GOVERNMENT.
SO IT'S NOT EXACTLY THE SAME
THING AS THE PROTESTS THAT CAME
ABOUT WITH TDF/FTC PRICING.
>>SO TO THE FIRST PART OF YOUR
COMMENT, WHAT'S KIND OF -- SO
THE MECHANISM, THEY KNOW EXACTLY
WHERE IT BINDS BECAUSE THEY SEE
WHERE MUTATIONS MAKE IT
INEFFECTIVE, RIGHT?
BUT EXACTLY -- EXACTLY, EXACTLY
HOW IT'S WORKING IS STILL BEING
LOOKED AT.
ONE OF THE MOST INTERESTING
THINGS IS THAT IT SEEMS TO
ALMOST ACCELERATE THE FORMATION
OF THE TWO PARTS, THE HEXAMER
PART AS THE CORE IS FORMING.
SO IT'S ALMOST LIKE IT WORKS
BETTER AND, THEREFORE, CREATES A
DEFECTIVE PARTICLE.
SO I MEAN, I THINK WE WILL HEAR
A LOT ABOUT IT IN TERMS OF THE
BASIC SCIENCE.
AS FAR AS THE QUESTION OF THE
USE AND THE COSTS AND ALL THAT,
YOU KNOW, AGAIN, THIS IS NOT
WHAT -- I MEAN, WE DO THE BASIC
SCIENCE, AND SO THAT'S REALLY
OUT OF OUR HANDS.
I COMPLETELY, COMPLETELY AGREE
THAT IT'S A TRAVESTY, BUT I
THINK IT'S A POLITICAL QUESTION
AND NOT A PERSONAL ONE, AND NOT
REALLY A QUESTION FOR THE WORK
THAT WE'RE DOING, UNFORTUNATELY.
>>THANK YOU, DR. FINZI.
LAST QUESTION, DR. D D'AQUILA.
>>THANK YOU.
MORE GENERIC BUT PROMPTED BY THE
FINE-SEQ ASSAY AND THOSE
FINDINGS, YOU KNOW, REFLECTING
BACK ON ALL WE'VE ACCOMPLISHED,
DAIDS HAD AN AWFUL LOT TO DO
WITH DEVELOPING AND ENABLING
CLINICAL INTRODUCTION OF OUR
VIRAL LOAD ASSAYS, OUR
OLD-FASHIONED RESISTANCE
GENOTYPING, IS THERE ANY
CONSIDERATION AS ALL THESE NEW
ASSAYS, IT'S NOT JUST FIND-SEQ,
WE'RE SEEING THESE KIND OF
PROLIFERATING.
AS ALL THESE ARE COMING OUT,
DOES DAIDS THINK THERE COULD BE
A WAY TO PROVIDE EITHER CORE
INFRASTRUCTURE OR TO ENABLE, YOU
KNOW, SOME OF YOUR NETWORKS,
MAYBE CFAR, SELFISHLY, TO, YOU
KNOW, HELP RESEARCHERS GET
ACCESS TO THESE DIFFICULT AND
EXPENSIVE ASSAYS, TO PUSH THE
RESEARCH FASTER.
>>I THINK THAT'S A REALLY
INTERESTING QUESTION.
CARL HAS HIS HAND RAISED.
>>I THINK, RICH, YOU'RE EXACTLY
RIGHT.
THERE'S A PROCESS OF INNOVATION
FOLLOWED BY IMPLEMENTATION, AND
HAVE CFAR DECIDE TO BRING IT IN
AS A CORE WOULD BE A START.
NETWORKS CAN DIVIDE TO ADD TO
THEIR TRICKS.
WE WOULD OF COURSE BE ALWAYS
INTERESTED IN THIS KIND OF
INNOVATION AS WE ROLL FORWARD.
>>THANKS, CARL.
>>GREAT.
THANK YOU.
I'M GOING TO KEEP US MOVING.
I KNOW THERE ARE A LOT OF
INTERESTING QUESTIONS AND
DISCUSSION, BUT I'D LIKE TO
TURN -- AND THANK YOU,
DR. FINZI, THAT WAS GREAT.
>>THANK YOU.
>> -- TURN IT OVER TO DR. PETER
KIM, THE THERAPEUTICS RESEARCH
PROGRAM, AND DR. KIM.
>>ALL RIGHT.
WELL, THANK YOU.
I'LL PRESENT AN UPDATE ON THE
THERAPEUTICS RESEARCH PROGRAM
TODAY.
HOPEFULLY THIS WORKS.
AND ARE PEOPLE SEEING MY SLIDES?
>>YES.
>>GREAT.
SO BEFORE I GET STARTED, I JUST
WANT TO ACKNOWLEDGE ALL THE
PEOPLE THAT REALLY MAKE
EVERYTHING I'M ABOUT TO PRESENT
TODAY POSSIBLE.
THE 42 PEOPLE HERE ON THE SCREEN
ARE REALLY THE WORKHORSES AND
THE PEOPLE THAT ACTUALLY DO ALL
THE WORK THAT I HAVE THE
PRIVILEGE OF PRESENTING TO YOU
TODAY.
THEY WORK TIRELESSLY, OF COURSE
TOGETHER WITH THE INVESTIGATORS
THAT WE FUND TO REALLY DRIVE THE
SCIENCE OF HIV THERAPEUTICS
FORWARD ON A DAILY BASIS.
SO AS CARL NOTED, WE WERE REALLY
FORTUNATE TO HIRE DR. VERNON
FROM THE CDC AS OUR NEW TB
CLINICAL RESEARCH BRANCH CHIEF,
AND ALSO WE RECENTLY APPOINTED
DR. LI ZHANG AS ASSOCIATE
DIRECTOR.
DAVID MAILHOT IS CLINICAL
PROJECT MANAGER TO HELP US WITH
SOME OF OUR PANDEMIC RESPONSE
TRIALS, MEDICAL OFFICER, ROGER
PTAK AS SENIOR RESEARCH ADVISOR.
SO THE OVERALL GOAL OF THE
THERAPEUTIC RESEARCH PROGRAM IS
TO IMPROVE THE HEALTH OF PEOPLE
LIVING WITH HIV, AND WE DO THAT
BY DEVELOPING NEW AND IMPROVED
THERAPEUTICS AND DIAGNOSTICS,
AND ADVANCING STRATEGIES TO
ACHIEVE DURABLE VIRAL
SUPPRESSION AND ART-FREE
REMISSION, ALSO KNOWN AS HIV
CURE.
BUT BEYOND THAT, WE ALL KNOW
THAT PEOPLE WITH HIV ALSO SUFFER
FROM A NUMBER OF COINFECTIONS
AND COMORBIDITIES THAT ARE
REALLY AFFECTING THEIR LIVES
EVERY DAY, AND SO WE DO HAVE A
SIGNIFICANT FOCUS ON THOSE VERY
INFECTIONS AND COMORBIDITIES.
IN TOTAL IN 2022, WE FUNDED A
TOTAL OF 147 GRANTS AND SEVEN
CONTRACTS, AND 92 TRIALS, WHICH
RESULTED IN 125 PUBLICATIONS.
SO TRP ACTIVITY AS NOTED ARE
WEIGHTED TOWARDS CLINICAL TRIALS
AS OPPOSED TO THE BASIC SCIENCE
PROGRAM WHO AS YOU HEARD FROM
DIANA TODAY.
WE HAVE MORE THAN 90 ACTIVE
CLINICAL TRIALS THAT ARE ALSO --
SOME OF THEM ARE IN DEVELOPMENT,
AND AS YOU CAN SEE, THEY SPAN
THE RANGE OF HIV CURE TO
TREATMENT, BUT ALSO TB,
HEPATITIS, DIAGNOSTICS, AND AS
I'LL NOTE LATER TODAY AS CARL
MENTIONED, WE HAVE BEEN ASKED TO
TAKE THE LEAD ON DEVELOPING
OUTPATIENT TREATMENTS FOR
PANDEMICS, SO WE STARTED WITH
COVID-19, AND THEN ALSO
MONKEYPOX.
SO BEYOND THE CLINICAL TRIALS,
HOWEVER, IN ORDER TO HELP US
KEEP THE CLINICAL TRIAL PIPELINE
AT THE CUTTING EDGE, WE MAINTAIN
A NUMBER OF PRE-CLINICAL
CONTRACTS AND GRANTS TO
FACILITATE THIS RESEARCH.
ONE OF THE EXAMPLES OF THIS IS A
VERY LARGE CONTRACT THAT WE FUND
TOGETHER WITH BSP THAT PROVIDES
GAP FILLING SERVICES FOR HIV AND
HIV ASSOCIATED COINFECTIONS.
AND AS YOU CAN SEE, THIS SINGLE
CONTRACT IS MADE UP OF MULTIPLE
SUBCOMPONENTS THAT COULD
FACILITATE ANYTHING FROM IN
VITRO TESTING AND SCREENING TO
CHEMICAL SYNTHESIS TO ANIMAL
MODEL TESTING TO PRE-CLINICAL
PHARMACOLOGY AND TOXICOLOGY TO
MANUFACTURING.
AND WE RECENTLY RELEASED AN FOA,
PDR22-185, TO MAKE IT EVEN MORE
CLEAR TO THE INVESTIGATIVE FIELD
HOW TO GET ACCESS TO THIS
IMPORTANT RESOURCE.
ANOTHER GOOD EXAMPLE OF A
INFRASTRUCTURAL GRANT IS AN R24
THAT WE FUND CALLED LEAP.
AND MANY OF YOU PROBABLY ALREADY
KNOW ABOUT THIS PROGRAM.
IT ESSENTIALLY A PROGRAM -- ITS
ESSENTIALLY A PROGRAM WE HELP
MAINTAIN TO HELP FACILITATE THE
SCIENTIFIC COMMUNITY TO DEVELOP
LONG-ACTING FORMULATIONS.
AND THEY RECENTLY RELEASED A CID
SUPPLEMENT WITH SEVERAL REALLY
FANTASTIC ARTICLES DELINEATING
BOTH ACHIEVEMENTS IN LONG-ACTING
FORMULATION TECHNOLOGIES AND
ALSO FUTURE NEEDS.
AND SO FROM HERE ON OUT, I WILL
TAKE MY TIME TO JUST DESCRIBE
SOME RECENT ADVANCES AND ONGOING
ACTIVITIES AND ANTICIPATED
PRIORITIES FOR EACH OF THE FOUR
PRIMARY AREAS OF FOCUS FOR TRP.
FIRST AND FOREMOST, HIV BUT ALSO
TUBERCULOSIS, HEPATITIS AND
PANDEMIC RESPONSE.
SO TO START WITH HIV, OUR LONG
TERM GOALS INCLUDE DEVELOPING
NEW AND IMPROVED TREATMENTS AND
STRATEGIES, POINT OF CARE HOME
BASED DIAGNOSTICS, ART-FREE
REMISSION AND CURE AND ADDRESS
KIKO MORBIDITIES THROUGH
COLLABORATIONS.
RECENTLY THEY WERE ABLE TO
DEVELOP NANOFORMULATIONS WHICH
SUPPORTS Q6-MONTH INJECTIONS IN
NON-HUMAN PRIMATES.
AS YOU CAN SEE, THESE ADVANCES
AS YOU HEARD FROM DIANA, THESE
ADVANCES ARE IN LINE WITH OTHER
WORK THAT'S GOING ON.
IT'S BEEN A REALLY FANTASTIC
COUPLE OF YEARS AS DR. GANDHI
NOTED FOR LONG-ACTING
FORMULATIONS, AND WE BELIEVE
THAT DEVELOPING MORE LONG-ACTING
FORMULATIONS, THAT COULD BE
PAIRED TOGETHER.
THAT COULD ALSO BE USED IN THE
MOST NEEDY POPULATIONS AS PEOPLE
HAVE NOTED IN COUNCIL IS REALLY
IMPORTANT, AND WE'RE EXCITED TO
SEE THESE NEW TWO DRUGS BEING
DEVELOPED INTO LONG-ACTING
FORMULATIONS.
BUT OF COURSE IT'S NOT JUST
ABOUT THE DRUGS BUT WE'RE
FOCUSED ON HIV CURE, AND OTHER
NOVEL TECHNOLOGIES THAT MAY BE
PAIRED WITH DRUGS TO ENHANCE HIV
TREATMENT, THE BROADLY
NEUTRALIZING ANTIBODIES FOR HIV
REPRESENT THAT FIELD AND CLASS
OF TREATMENTS, AND DR. GABLER
AND COLLEAGUES RECENTLY
DESCRIBED THE TRIAL WHERE THEY
WERE ABLE TO COMBINE TWO BROADLY
NEUTRALIZING ANTIBODIES, 101074
AND - 3BNC117, AND EVEN WITH THT
SUPPRESSION THEY WERE ABLE TO
FIND THE TWO BNABs WERE ABLE
TO EFFECT VIRAL SUPPRESSION OVER
A LONG PERIOD OF TIME.
SO SOME ONGOING WORK AND FUTURE
PRIORITIES FOR HIV.
OF COURSE WE WANT TO GO BEYOND
THE BROADLY NEUTRALIZING
ANTIBODIES TO REALLY BE ABLE TO
EFFECT THERAPEUTIC VACCINES THAT
MIGHT HAVE A THERAPEUTIC
BENEFIT, EVEN CURE, FOR PEOPLE
WITH HIV.
SO WE'RE HARD AT WORK, WORKING
WITH OUR INVESTIGATORS TO
DEVELOP BNAB INDUCING VACCINES,
AND ALSO T-CELL INDUCING
VACCINES, AND THEN NOVEL
COMBINATIONS OF THESE DIFFERENT
VARIETIES OF INTERVENTIONS.
OF COURSE THROUGH THE PROPER
RESEARCH ON DRUG RESISTANCE,
BNAB RESISTANCE, AND OTHER ANS
LEAR RESEARCANCILLARY RESEARCH T
ONCE WE HAVE THESE INTERVENTIONS
DEVELOP, WE WILL BE RAPIDLY ABLE
TO DEVELOP THEM TO THE BEDSIDE.
BEYOND JUST THESE MORE -- THE
NOVEL TYPE OF TECHNOLOGIES, WE
ARE ALSO COMMITTED TO DEVELOPING
LONG-ACTING REGIMENS, BNABs AS
TREATMENTS, NOVEL DIAGNOSTICS,
AND TREATMENT STRATEGIES THAT
ALL, I THINK, WILL PLAY A PART
TO EVENTUALLY BRING AN END TO
THE HIV EPIDEMIC.
AS YOU CAN SEE, OUR PAROLE
CONSISTS OF MULTIPLE CLINICAL
TRIALS.
THESE ARE JUST SOME OF THE
EXAMPLES WE HAVE ONGOING THROUGH
THE ACTG.
WE ALSO HAVE NON-NETWORK
CLINICAL TRIALS THAT WE FUND
THAT ALSO ARE WORKING TO JUST
ESTABLISH NOVEL STRATEGIES, AND
ALSO OF COURSE THE PRE-CLINICAL
RESEARCH PORTFOLIO AGAIN IS
CRITICAL TO KEEP THAT CLINICAL
PORTFOLIO AT THE CUTTING EDGE.
SO MOVING ON TO TUBERCULOSIS.
AS MOST PEOPLE IN THE COUNCIL
KNOW, TB IS THE LEADING CAUSE OF
THAT, AND MORBIDITY AMONG PEOPLE
WITH HIV.
IN 2021, THERE WERE OVER 187,000
DEATHS FROM TB JUST AMONG PEOPLE
WITH HIV, NOT INCLUDING THOSE
THAT -- GIVEN THE DEATHS AMONG
THOSE THAT DON'T HAVE HIV.
ACTUALLY THE COVID PANDEMIC MADE
A NEGATIVE DIFFERENCE OR IMPACT
ON TB OVERALL, INCLUDING IN
PEOPLE LIVING WITH HIV, AND SO
WE ARE REALLY WORKING HARD TO
ADVANCE TECHNOLOGIES AND
IMPROVEMENTS THAT WILL GET US
BACK ON TRACK FOR TB, FIRST AND
FOREMOST FOR PEOPLE LIVING WITH
HIV.
SO OUR LONG TERM GOALS WITH TB
INCLUDE NEW PREVENTION
STRATEGIES, DEVELOPING NEW
DIAGNOSTICS AND TREATMENTS FOR
TB AND HIV AND ADVANCING
CLINICAL OBSERVATIONAL RESEARCH
IN REGIONS MOST AFFECTED BY
TB/HIV.
SO SOME SELECT ADVANCES.
DR. DENARDO AND COLLEAGUES
RECENTLY DESCRIBED THROUGH A
COHORT OF 435 NTB PATIENT, THAT
THEY WERE ABLE TO IDENTIFY TWO
DISTINCT ENDO TYPES, ONE FOR
TREATMENT FAILURE AND SLOWER
TIME TO CULTURE CONVERSION, AND
ANOTHER FOR IMPROVED CLINICAL
OUTCOMES.
THE IMPORTANT THING IN THESE
FINDINGS IS IT COULD HELP US
IDENTIFY THOSE WHO MAY BENEFIT
FROM SHORTER COURSE THERAPY AND
ENABLE PATIENT-SPECIFIC
APPROACHES TO IMPROVED TREATMENT
OUTCOMES.
BUT OF COURSE IT'S NOT JUST
ABOUT THESE NOVEL ASSAYS THAT
ARE IMPORTANT.
WE BELIEVE THERE'S A LOT OF
KNOWLEDGE THAT CAN BE GAINED
JUST FROM CLINICALLY
IDENTIFIABLE AND OBSERVABLE
EFFECTS, AND OUR COLLEAGUES AT
THE REPORT BRAZIL CONSORTIUM
ALSO WERE ABLE TO IDENTIFY THAT
THERE WERE DISTINCT PREDICTORS
FOR EACH TYPE OF UNSUCCESSFUL
OUTCOME WHEN THEY APPLIED A
COMPOSITE OF DIFFERENT CLINICAL
OUTCOME MEASURES IN THEIR
COHORT.
WHICH IS REALLY IMPORTANT.
I THINK THE FUTURE HOLDS THAT WE
WILL BE ABLE TO EVENTUALLY
COMBINE BOTH CLINICAL AND ALSO
BLOOD-BASED BIOMARKERS TO REALLY
HONE OUR TREATMENT OF TB
INFECTED PATIENTS INCLUDING
PEOPLE WITH HIV IN THE FUTURE.
SO ONGOING WORK AT FUTURE
PRIORITIES FOR TB, I THINK
ANYONE THAT FOLLOWS THE
LITERATURE FOR TB KNOWS THAT
IT'S BEEN -- DESPITE THE
COVID-19 PANDEMIC, IT'S BEEN A
FEW GOOD YEARS FOR TB.
NOT ONLY IS THE TB PIPELINE THE
FULLEST IT BEEN SINCE THE
BEGINNING OF TB RESEARCH, BUT
ALSO THERE HAVE BEEN A NUMBER OF
REALLY JUST VERY IMPORTANT
ADVANCEMENTS IN TB CLINICAL
TRIALS.
WE ARE NOW ABLE TO TREAT LTBI IN
LESS THAN ONE MONTH.
WE ALSO CONTRIBUTE TO A STUDY
THAT SHOWED WE CAN TREAT REGULAR
TB DISEASE WITH FOUR MONTHS
THERAPY, BUT TO BUILD ON THESE
SUCCESSES, WE ALSO HAVE 16
TRIALS ONGOING TO DEVELOP AND
EVALUATE NOVEL REGIMENS.
WE ALSO HAVE A SIGNIFICANT
PORTFOLIO, SURROGATE BIOMARKER
RESEARCH TO ENABLE MORE
EFFICIENT TRIAL DESIGNS OR
FASTER BREAKTHROUGHS, IMPROVED
CLINICAL CARE, AND MOST
IMPORTANTLY, WE ARE WORKING WITH
OTHER FUNDING PARTNERS BOTH AT
THE GATES FOUNDATION AND IN
EUROPE AND AROUND THE WORLD TO
DEVELOP INFRASTRUCTURES AND
STRUCTURES TO FACILITATE
COMMUNICATION, COORDINATION AND
COLLABORATION AMONG THE GLOBAL
RESEARCH ORGANIZATIONS TO
REALIZE SYNERGIES ACROSS THE
RESEARCH FIELD.
JUST TWO EXAMPLES OF IMPORTANT
TRIALS THAT WE HAVE ONGOING FOR
TB ARE THE SPECTRA STUDY, WHICH
IS A PHASE 2B DURATION
RANDOMIZED STUDY LOOKING AT A
COMBINATION OF INH -- TO SEE HOW
LOW OR HOW SHORT WE CAN REALLY
GO WITH THIS REGIMEN FOR PEOPLE
WITH BOTH LOW AND HIGH RISK TB.
ALSO, ACTG5405409 ALSO KNOWN ASE
RAD-TB STUDY, NEW NOVEL IMI
NATIONS OF THE TB DRUGS I JUST
SHOWED YOU TO SHOW WHICH
COMBINATIONS WOULD WORK THE BEST
FOR THE TREAT.
OF ACTIVE TB.
AND THIS STUDY IS COUPLED WITH A
WHOLE 'NOTHER PRE-CLINICAL
EFFORT, MODELING EFFORT TO
REALLY GET TO FASTER ADVANCEMENT
OF NEW NOVEL REGIMENS FOR TB.
MOVING ON TO HEPATITIS.
BEYOND TB, I THINK ALSO MANY OF
US RECOGNIZE THAT HEPATITIS IS
ALSO MAYBE THE NUMBER TWO MOST
IMPORTANT CAUSE OF DEATH AND
MORBIDITY AMONG PEOPLE WITH HIV,
SO WE ARE INCREASINGLY FOCUSED
ON THIS DISEASE TO MAKE SURE
THAT PEOPLE WITH HIV ARE NOT
UNDULY SUFFERING FROM HEPATITIS,
BOTH HEPATITIS B AND HEPATITIS C
AS DR. DIEFFENBACH IS A PRIORITY
FOR US, I IMPROVE TREATMENTS FOR
HEPATITIS C AND B ARE ANOTHER
PRIORITY, AND WE'RE ALSO LOOKING
FOR IMPROVED PREVENTIVE
HEPATITIS B VACCINES FOR PEOPLE
LIVING WITH HIV, AND ALSO OF
COURSE DIAGNOSTICS FOR BOTH
DISEASES.
SO SOME SELECT ADVANCES.
AS SOME PEOPLE MAY RECOGNIZE THE
ADVENT OF LONG-ACTING ANTI-HIV
TREATMENTS HAVE REALLY NOW PUT
THE HEPATITIS B FIELD ON EDGE
BECAUSE WHAT MAY HAPPEN IS THAT
THE CHANGE TO USING CATANUBA MAY
THEN LEAVE MANY, MANY PATIENTS
THAT HAVE HEPATITIS B BUT ARE
CURRENTLY UNDIAGNOSED WITHOUT AN
EFFECTIVE ANTIVIRAL AS PART OF
THEIR REGIMEN.
SO WE BELIEVE IT AN IMPORTANT
PRIORITY TO DEVELOP LONG-ACTING
ANTIREP TIGHTS B ANTIRETROVIRALS
THAT CAN BE COUPLED WITH ANTIHIV
TREATMENTS.
ONE SUCH EXAMPLE IS FROM DR. DAS
AND COLLEAGUES WHO SHOWED A
LONG-ACTING TENOFOVIR
NANOFORMULATION THAT AT LEAST IN
HUMANIZED MICE LOOKS LIKE IT
COULD ACHIEVE ACUTE THREE-MONTH
TREATMENT DURATION.
NOW THIS OBVIOUSLY NEEDS TO BE
FURTHER DEVELOPED AND TRANSLATED
FOR USE IN HUMANS, BUT THIS IS A
REALLY PROMISING START FOR A
VERY IMPORTANT FIELD.
MOVING ON TO THE CLINICAL AREA,
WE RECENTLY HAD A STUDY 5379,
IT'S AN ONGOING PHASE 3 STUDY
THAT WAS DESIGNED TO STUDY AND
COMPARE THE EFFICACY AND SAFETY
OF HEPLASAV-B AND ENGERIX-B IN
HBV VACCINE NON-RESPONDERS.
ANOTHER PRIMARY AIM OF THE STUDY
WAS LOOKING NE SMALLER PROP
LAITION JUST IN
HBV-VACCINE-NAIVE PATIENTS AND
THEY STUDIED A COCKTAIL OF THREE
VACCINATION REGIMEN OF
HEPLISAV-B.
WHAT THEY FOUND IS AMONG THOSE
WITH HBSAB RESULTS, 100%
ACHIEVED SPR AFTER THREE DOSES.
SPR IS THE NEUTRALIZING ANTIBODY
RESPONSE THAT IS EXPECTED TO
PROVIDE FULL PROTECTION AGAINST
HEPATITIS B.
AND EVEN AFTER TWO DOSES, THEY
FOUND THE MAJORITY HAD
PROTECTIVE RESPONSE.
THERE WERE NO SAFETY ISSUES OR
DEATHS TO DATE AND REMAIN IN
FOLLOW-UP TO ASSESS DUSHABILITY
OF RESPONSE AND SAFETY.
SO SOME ONGOING WORK IN
HEPATITIS B, WE HAVE A NUMBER OF
CLINICAL TRIALS THAT ARE
EVALUATING OTHER NOVEL REGIMENS
FOR HEPATITIS B CURE, BUT ALSO
WE BELIEVE THAT WE NEED TO DO
SOME ADDITIONAL WORK IN CLINICAL
OBSERVATIONAL RESEARCH AND IN
THE LABORATORY TO GET A BETTER
UNDERSTANDING OF THE
PATHOGENESIS AND THE PATHOLOGY
OF HEPATITIS B AND PEOPLE WITH
HIV, AND ALSO TO DEVELOP NOVEL
BIOMARKERS THAT WILL HELP US IN
OUR ENDEAVOR TO CURE HEPATITIS
B.
OKAY.
LAST BUT NOT LEAST IS THE
PANDEMIC RESPONSE, AND IF YOU
REMEMBER MY PRESENTATIONS FROM A
YEAR PAST, EARLY IN THE PANDEMIC
OUR GROUP ALONG WITH THE ACT
GWAS ASKED TO TAKE ON THE GOAL
OF DEVELOPING OUTPATIENT
TREATMENTS FOR COVID-19.
THEN THIS PAST YEAR MONKEYPOX
HIT AND WE WERE SIMILARLY ASKED
TO DEVELOP A CLINICAL TRIAL FOR
EVALUATION OF TPOXX.
SO TO DATE, AS A GROUP THAT WAS
NOT FOCUSED ON PANDEMIC RESPONSE
PRIOR TO COVID-19, NOW WE HAVE
EVALUATED TREATMENTS FOR TWO
NOVEL DISEASES, WE DESIGNED
SEVEN UNIQUE TRIALS, FIVE OF
THEM WERE IMPLEMENTED.
WE TESTED MORE THAN 10 AGENTS
ALONG WITH NINE INDUSTRY
PARTNERS.
THE ACTIV-2 STUDY WHICH YOU'VE
HEARD A LOT TODAY FROM
DR. DIEFFENBACH AND ALSO FROM
PREVIOUS YEARS' PRESENTATION THE
IS NOW FINISHING UP ALL THE
PARTICIPANTS ARE NOW IN
FOLLOW-UP PHASE AND WE ARE NOT
TAKING ANY NEW ENROLLMENTS INTO
THE STUDY.
INVESTIGATORS AT THE ACTG ARE
REALLY NOW FOCUSED ON GETTING
AND -- ANALYZING THE DATA AND
GETTING THE RESULTS OUT THERE.
US A CAN SEE, WE'VE HAD A NUMBER
OF PUBLICATIONS EVEN MORE
POSTERS AND ACTUALLY EVEN IN THE
TWO WEEKS SINCE I'VE PREPARED
THIS PRESENTATION, I THINK I'VE
HEARD THERE ARE AT LEAST TWO OR
THREE MORE PUBLICATIONS THAT ARE
GOING TO PRESS AS WE SPEAK.
SO WE EXPECT TO SEE A LOT MORE
OF THE RESULTS COMING FORTH FROM
THIS TRIAL IN THE VERY NEAR
FUTURE.
ANOTHER REALLY IMPORTANT STUDY
TO US IS THAT ACTIV 2D STUDY,
THIS IS A PHASE III STUDY TO
EVALUATE A NEW SARS-COV-2 3CL
PROTEASE INHIBITOR.
YOU MAY HAVE HEARD IN THE NEWS
THAT SHI KNOW GEE RECENTLY HAD
POSITIVE RESULTS FROM ANOTHER
PHASE 3 IN LOW RISK PARTICIPANTS
IN A CLINICAL TRIAL THAT WAS
PRIMARILY CONDUCTED IN ASIA.
SO THIS IS THE SECOND PHASE III
WE ARE CO CONDUCTING TOGETHER WH
THEM.
THE PRIMARY OUT COME, MEDIAN
TIME TO SUSTAINED SYMPTOM
RESOLUTION.
THIS IS A GLOBAL STUDY, WE HAVE
SITES CURRENTLY OPEN IN THE U.S.
AND JAPAN, WE HAVE ACTIVATED
SITES IN SOUTH AFRICA AND WE
EXPECT MANY MORE SITE
ACTIVATIONS IN THE ENSUING
MONTHS ALL OVER THE WORLD.
AND WE COULD REALLY USE YOUR
HELP TO GET THIS STUDY ENROLLED
AS QUICKLY AS POSSIBLE, SO
ANYONE INTERESTED IN HELPING
PLEASE VISIT OUR STUDY WEBSITE
AND -- FOR PATIENTS AND
POTENTIAL PARTICIPANTS TO THIS
STUDY.
LAST BUT NOT LEAST IS THE ACTG
PLATFORM HUMAN MONKEYPOX STUDY I
WAS TELLING YOU ABOUT.
WE WERE ASKED TO EVALUATE TPOXX
FOR THE OUTPATIENT TREATMENT OF
MPOX.
THIS IS ANOTHER GLOBAL STUDY.
WE ARE CURRENTLY ENROLLING
PARTICIPANTS ALL THROUGHOUT THE
U.S. THROUGH A REMOTE ENROLLING
MECHANISM AND WE ACTUALLY HOPE
TO OPEN SITES IN BRAZIL, PERU,
MEXICO, OTHER SITES AROUND THE
WORLD IN THE VERY NEAR FUTURE.
THIS IS A VERY IMPORTANT STUDY
BECAUSE WE ARE ONE OF THE MAIN
STUDIES GLOBALLY THAT WILL BE
STUDYING TPOXX FOR THE EFFICACY
AGAINST MONKEYPOX.
AND UNLESS WE GET THIS STUDY
DONE, WE RISK THAT THIS DRUG MAY
NEVER HAVE TRULY GOOD CLINICAL
TRIAL DATA TO SUPPORT ITS USE IN
MONKEYPOX PATIENTS AROUND THE
WORLD.
OKAY.
FINALLY JUST GETTING TO THE END
OF MY PRESENTATION, I WAS ASKED
TO TALK A LITTLE BIT ABOUT
LESSONS LEARNED, AND CERTAINLY
THERE ARE MANY, MANY LESSONS
LEARNED.
I'VE TRIED TO ENCAPSULATE THOSE
LESSONS IN TWO SLIDES.
ONE IS WHAT WORKED WELL, AND
ALSO THE SECOND SLIDE I'LL TALK
A LITTLE BIT ABOUT WHAT I THINK
WE COULD DO BETTER FOR THE NEXT
TIME.
SOME OF THESE LESSONS ARE
OBVIOUSLY WE HAVE ALREADY TAKEN
INTO ACCOUNT AS THROUGH
SUBSEQUENT CLINICAL TRIALS, BUT
ONE THING THAT REALLY CAME TO
THE FORE FORE IS THAT THE ACTG Y
DID JUST AN AMAZING JOB IN BOTH
THEIR CLINICAL TRIAL DESIGNS AND
ALSO THEIR SCIENTIFIC EXPERTISE
WAS RIGHT ON THE MARK.
AND EVEN BEYOND THE CLINICAL
TRIALS THAT WE IMPLEMENTED
OURSELVES WITH THE ACTG, ACTG
CLINICAL TRIAL SCIENTISTS AND
DADAID SCIENTISTS TO HELP DEVELP
THEIR OWN CLINICAL TRIAL DESIGNS
BASED ON THEIR EXPERTISE.
I HAVE TO REALLY GIVE AN
APPLAUSE TO DAID'S COLLEAGUES
AND EXPERTS ON THE LEADERSHIP
OPERATIONAL SIDE WHO REALLY
WORKED HARD TO MAKE THESE
CLINICAL TRIALS POSSIBLE AND TO
GET THEM UP AND GOING IN RECORD
TIME.
WE FOUND THAT THE DAID SYSTEM
WORKS AND IT IS A GOOD SYSTEM.
THE DAIDS EXPERTS THAT PUT THEIR
TIME INTO THIS REALLY DID AN
AMAZING JOB OF GETTING THINGS.
WE ALSO FOUND THE ROBUST
FRAMEWORK FOR AGENT SELECTION
THAT WAS DONE UNDER THE
FRAMEWORK OF THE ACTIV PPP WAS
BOTH TIME AND RESOURCE SAVING
AND I THINK WE COULD NOT HAVE
FOCUSED ON THE SCIENCE AS WE DID
UNLESS WE HAD THE COLLABORATION
FROM THE ACTIV PARTNERS.
WE FOUND THE BROAD AND LARGE
GLOBAL ENROLLMENT STRATEGY IS
ABSOLUTELY NEEDED IF YOU WANT
RAPID ENROLLMENT.
AND SO -- BUT WE ALSO FOUND THIS
PHRASE TO BE TRUE, DON'T CHASE
THE PANDEMIC, LET IT COME TO
YOU, AND THIS IS A PHRASE WE
OFTEN REFER TO, WHEN WE ARE
COMING UP WITH OUR CLINICAL SITE
STRATEGY.
WE FOUND THAT A SITE'S
INFRASTRUCTURE THAT INCLUDES
BOTH ACADEMIC AND
COMMUNITY-BASED RESEARCH SITES
WAS CRITICAL TO THE SUCCESS OF
OUR CLINICAL TRIALS, AND LOCAL
AND COMMUNITY-BASED OUTREACH TO
DRIVE ENROLLMENTS WAS THE SINGLE
MOST EFFECTIVE STRATEGY TO DRIVE
ENROLLMENT INTO OUR TRIALS.
WE FOUND THAT UTILIZING EXISTING
PROCESSES AND INFRASTRUCTURE AS
OPPOSED TO DEVELOPING NEW
PROCESSES AND INFRASTRUCTURE
RESULTED IN THE FASTEST TRIAL
BUILD AND INITIATION.
ALL OF THESE LESSONS CULMINATED
INTO THE LAST TRIAL WE'VE
DEVELOPED AND IMPLEMENTED, AND
BASED ON THESE LESSONS, WE WERE
ABLE TO GET THE A5418 TRIAL FROM
CONCEPT TO FIRST PATIENT IN
WITHIN SIX WEEKS, WHICH I THINK
IS A RECORD TIME, AND EVEN OUR
COLLEAGUES AT THE FDA WERE QUITE
ASTONISHED AT THE SPEED WITH
WHICH WE WERE ABLE TO GET THAT
TRIAL UP AND GOING.
AND THAT'S BECAUSE OF ALL THE
LESSONS THAT WE'VE LEARNED TO
DATE FROM THE PANDEMIC RESPONSE.
AND LAST BUT NOT LEAST, WE FOUND
THAT REAL WORLD EVIDENCE WAS
CRITICAL TO INFORMING OUR TRIAL
DESIGNS, AND WITHOUT IT, WE
REALLY WOULD NOT HAVE BEEN ABLE
TO DO MUCH OF THE WORK WE HAVE
DONE TO DATE.
SO SOME OPPORTUNITIES FOR
IMPROVEMENT.
AS I DISCUSSED, WE BELIEVE THAT
A BROAD GLOBAL ENROLLMENT
STRATEGY IS ABSOLUTELY NEEDED.
IF YOU WANT TO ENROLL QUICKLY,
YOU NEED A LOT OF SITE.
I THINK IT JUST -- YOU KNOW, IT
JUST MAKES A LOT OF SENSE.
BUT WE FOUND THAT THE EX--U.S.
REGULATORY TIME LINES REPRESENT
SIGNIFICANT DELAYS TO STUDY
INITIATION.
OBVIOUSLY IT'S NOT SOMETHING WE
CAN DO MUCH ABOUT JUST SITTING
HERE AT NIAID, BUT WE DO THINK
THAT IT'S SOMETHING THAT WE NEED
TO CONTINUOUSLY ENGAGE WITH OUR
GLOBAL PARTNERS TO SEE IF WE
COULD BRING THESE TIME LINES
DOWN ALSO BUILDING A NEW AND
LARGE SITE INFRASTRUCTURE IS
BOTH TIME AND RESOURCE INTENSIVE
SO WE NEED TO BE ABLE TO COME UP
WITH STRATEGIES WHERE WE WILL BE
ABLE TO ENGAGE THE NEEDED
INFRASTRUCTURE MUCH MORE QUICKLY
THAN WE WERE ABLE TO DO AT THE
BEGINNING OF THIS COVID-19
PANDEMIC.
WE NEED TO BE ABLE TO UTILIZE
EXISTING SYSTEMS AND PROCESSES,
NOT ONLY WITH THE TRIAL
INFRASTRUCTURE BUT -- NOT ONLY
WITH THE SITE INFRASTRUCTURE BUT
ALSO INCLUDING THE TRIAL
INFRASTRUCTURE SUCH AS THE STUDY
DATABASE AND OTHER ASPECTS OF
THE TRIAL.
JUST IN EVERY WAY, ANYTHING THAT
WE DEVELOP NEW, WE FOUND JUST
ADDED COMPLEXITIES THAT ONE
COULD NOT HAVE IMAGINED AT THE
BEGINNING OF THE TRIAL, BUT
WHICH RESULTED IN SIGNIFICANT
DELAYS.
COMPLEX PROTOCOL DESIGNS SI
SIMILARLY RESULTED IN SIGHT
STARTUP AND ENROLLMENT CAPACITY
AND PLATFORM DESIGN DID NOT
PRODUCE HYPOTHESIZED
EFFICIENCIES AS WE HAD HOPED,
HINDERING ABILITY TO ADAPT THE
TRIAL TO PANDEMIC REALITIES.
AGAIN, REAL WORLD EVIDENCE IS
SOMETHING THAT WE FOUND WAS
CRITICAL TO MANUFACTURING OUR
TRIAL DESIGNS, AND I HAVE TO SAY
AT THE BEGINNING OF THE
PANDEMIC, THE ABSENCE OF REAL
WORLD EVIDENCE REALLY HAMPERED
OUR ABILITIES FOR TRIAL DESIGN
AND AS THIS EVIDENCE BECAME MORE
AVAILABLE, IT WAS A REAL BOON
AND IMPORTANT RESOURCE FOR US.
BUT I THINK IN THE FUTURE,
TRYING TO GET ACCESS TO THIS
EVIDENCE FROM THE VERY ONSET OF
THE PANDEMIC WOULD BE REALLY
CRITICAL TO HELP US WITH OUR
TRIAL DESIGNS.
AND LAST BUT NOT LEAST, WE FOUND
THAT WE ABSOLUTELY NEED SURGE
CAPACITY.
BOTH HUMAN AND STRUCTURAL
RESOURCES.
TO ENABLE A RAPID STARTUP OF ANY
CLINICAL TRIAL THAT WE HAVE, AND
ALSO TO PRESENT BURNOUT.
AND I THINK IT GOES WITHOUT
SAYING THAT EVERY SINGLE PERSON
THAT WAS COMMITTED TO THE TRIALS
THAT I'VE DISCUSSED TODAY, THEY
WERE DOING ALL OF THIS WORK ON
TOP OF THEIR 40-HOUR WORK WEEKS
OR 50, 60-HOUR WORK WEEKS, AND
WE WERE ALL WORKING REALLY HARD
TO GET THIS UP AND GOING.
IT WAS POSSIBLE AT THE BEGINNING
BECAUSE, YOU KNOW, OF JUST WHAT
THE PANDEMIC REPRESENTED, BUT AS
THE PANDEMIC WENT ON, I FOUND
THAT STAFF STARTED TO BURN OUT,
AND SO I THINK IT'S VERY
IMPORTANT THAT WE RECOGNIZE THAT
OUR COLLEAGUES AND OUR
INVESTIGATOR COLLEAGUES REALLY
DO HAVE LIMITS AND WE NEED TO
BUILD IN THE SURGE CAPACITY,
SHOULD WE NEED THAT CAPACITY IN
THE FUTURE.
WITH THAT, I'LL JUST RECOGNIZE
ALL THE STAFF MEMBERS OF TRP
AGAIN.
THEY ARE REALLY THOSE PEOPLE ARE
THE ONES WHO MAKE THIS ALL
POSSIBLE.
AND I'LL TAKE QUESTIONS AND
DISCUSSION.
THANK YOU.
>>THANK YOU, DR. KIM.
THAT WAS GREAT.
REALLY IMPRESSIVE, ALL OF THE
WORK GOING ON.
IN ADDITION TO THE COVID WORK
AND HOW QUICKLY AND IMPRESSIVELY
THAT WAS DONE.
MONICA, YOU KNOW, I THINK WHAT
I'D LIKE TO DO IS -- WELL, WHAT
CAN WE DO HERE?
MAYBE WE'LL TAKE TWO -- MONICA
PASSED?
OKAY, DR. HARRIS, ONE QUESTION,
THEN WE'RE GOING TO TAKE A
FIVE-MINUTE BREAK AND WE WILL
CATCH UP THE TIME, I AM CERTAIN.
>>SO I JUST WANTED TO COMMENT
AND QUICK QUESTION ON
RESISTANCE.
SO WITH ZICOVAK, THE RESISTANCE
PROFILE IS DIFFERENT THAN
PAXLOVID.
THERE'S A FEW STUDIES INCLUDING
A BIOARCHIVE FROM US THAT SAYS
THAT SO I THINK IT'S GREAT THAT
OTHER DRUGS ARE MOVING WITH
DIFFERENT PROFILES.
AND THE OTHER IS ON
TUBERCULOSIS, SO I THOUGHT THAT
WAS REALLY INTERESTING, I WAS
WONDERING WHAT THE RESISTANCE IS
LIKE IN THOSE DRUGS THAT ARE AT
THE FRONT, LIKE PHASE III AND
ALREADY APPROVED.
IS THAT A PROBLEM?
>>THANK YOU FOR THAT QUESTION.
IT'S A GREAT QUESTION.
AND THE ANSWER IS, IT'S NOT A
GLOBAL PROBLEM YET, BUT IT'S
BECOMING A PROBLEM.
SO FOR EXAMPLE, ONE OF THE NEW
DRUGS AND MOST EFFECTIVE DRUGS
THAT ARE NOW AVAILABLE FOR
MULTIDRUG RESISTANCE TB ALREADY
HAS RESISTANCE IN SOME PART OF
THE WORLD.
SO WE ARE REALLY WORKING HARD TO
MAKE SURE THAT THE RESISTANCE
TESTING THAT NEEDS TO BE PAIRED
AND DEVELOPED TOGETHER WITH DRUG
DEVELOPMENT IS HAPPENING AT THE
SAME TIME.
AND WE ARE ALL AFRAID THAT
UNLESS WE DO THAT, THAT WE WILL
LOSE THESE DRUGS VERY QUICKLY.
>>SUPER.
THANK YOU.
>>GREAT.
THANK YOU.
THANKS, EVERYONE, FOR YOUR
PRESENTATIONS.
WHY DON'T WE TAKE A FIVE-MINUTE
BREAK AND COME BACK AT 2:54 AND
WE'LL GET STARTED AND WE'LL PICK
UP THE FOUR MINUTES.
THANKS, EVERYONE.
FIVE-MINUTE BREAK.
>>WE ARE BACK.
I REALIZE -- THAT WAS PROBABLY
NOT A REASONABLE THING TO DO, TO
ASK PEOPLE TO TAKE A FIVE-MINUTE
BREAK.
I REALIZED IT AFTER I SAID IT
AND THE CLOCK WAS GOING, I
THOUGHT, HMM, HOW DOES ONE UNDO
THAT.
SO FOR THOSE WHO THOUGHT THAT
WAS VERY UNREASONABLE, I
APOLOGIZE.
HOPEFULLY THEY'RE NOT BACK YET
AND WITH W WILL ARRIVE.
BUT LET US CONTINUE AND MOVE TO
THE VACCINE RESEARCH PROGRAM AND
DR. MARY MAROVICH.
AND WE LOOK FORWARD TO HEARING
YOUR PRESENTATION, AND AGAIN MY
APOLOGIES TO THOSE WHO ARE
RUSHING BACK.
>>THANKS SO MUCH, KEN.
REALLY SAD TO SEE THIS WILL BE
OUR LAST TIME TOGETHER.
APPRECIATE YOUR CHAIR HERE.
GOOD AFTERNOON.
IT'S MY PLEASURE TO PROVIDE THE
ANNUAL OVERVIEW ON THE VACCINE
RESEARCH PROGRAM AND SOME OF THE
EXCITING WORK THAT'S BEEN DONE
IN THE PROGRAM.
FIRST I'LL TALK BASICALLY ABOUT
THE PROGRAM MISSION AND PROVIDE
SOME HIGHLIGHTS ON THE U.S.
GOVERNMENT COVID-19 RESPONSE IN
TERMS OF THE VACCINE WORK, AND
THEN I'LL DIVE DEEPLY INTO OUR
HIV VACCINE STRATEGY,
PARTICULARLY IN DISCOVERY AND
DESIGN WHICH WILL INVOLVE A LOT
OF NON-HUMAN PRIMATE ANIMAL
STUDIES.
I'LL MAKE SURE I POINT THOSE OUT
TO, YOU AND HOW WE USE THAT
INFORMATION MOVING INTO OUR
VACCINE CONCEPTS IN CLINICAL
TESTING AND THEN GO OVER SOME
FUTURE DIRECTIONS FOR VACCINES.
BEFORE I MOVE INTO THE BULK OF
THE PRESENTATION, I'D LIKE TO
PROVIDE ACKNOWLEDGMENTS BECAUSE
THEY ARE VERY IMPORTANT AND I
DON'T WANT TO NOT HAVE ENOUGH
TIME FOR THAT.
FIRFIRST I'D THANK THE PEOPLE WO
MAKE THIS WORK POSSIBLE, NIAID
AND DAIDS SENIOR MANAGEMENT, AND
OF COURSE I'D LIKE TO CALL OUT
ALL THE HARD WORKING AND
DEDICATED MEMBERS OF THE VACCINE
RESEARCH PROGRAM THAT ARE SHOWN
HERE WHO HAVE NOT ONLY
CONTRIBUTED SUBSTANTIALLY TO THE
COVID-19 RESPONSE, BUT THEY
ACTUALLY KEPT ALL THE HIV
SCIENCE MOVING FORWARD, WHICH IS
REALLY REMARKABLE DURING THESE
VERY CHALLENGING THREE YEARS.
LASTLY I WANT TO THANK ALL OUR
NIAID-FUNDED NETWORK, PRINCIPAL
INVESTIGATORS, LABS, SITES AND
PARTNERS AND STUDY PARTICIPANTS
AND COMMUNITY MEMBERS BECAUSE
WITHOUT THEM, NONE OF THIS WOULD
BE POSSIBLE, SO THANKS VERY MUCH
TO ALL OF YOU.
OKAY.
SO WE CAN GO TO THE NEXT SLIDE
AND TALK ABOUT THE MISSION AND
ORGANIZATION.
OBVIOUSLY OUR GOAL IS TO DEVELOP
A SAFE AND EFFECTIVE HIV
VACCINE.
WE ARE COMPRISED OF REALLY -- WE
HAVE A PRE-CLINICAL RESEARCH AND
DEVELOPMENT BRANCH WHICH WORKS A
LOT IN THE DISCOVERY AND DESIGN
AREA, A LOT OF ANIMAL WORK IS
DONE THERE.
WE'RE LUCKY ENOUGH TO HAVE A
VACCINE TRANSLATIONAL BRANCH
WHICH -- DOES A LOT OF THE PROCS
DEVELOPMENT, PRODUCT DEVELOPMENT
AND IMPORTANTLY THE GMP
MANUFACTURING BECAUSE THAT'S
WHERE MOST OF THE PRODUCTS COME
THAT WE TEST IN OUR VACCINE
CLINICAL RESEARCH BRANCH, THE
THIRD BRANCH, WHERE ALL THE
CLINICAL TRIALS ARE MANAGED AND
OF COURSE THE IMMUNE
LABORATORIES ARE OVERSEEN THERE
AND THE CLINICAL LABORATORIES
THAT ARE THE ENGINES THAT MAKE
OUR CLINICAL TRIALS RUN AND HELP
US UNDERSTAND THE RESULTS.
THIS IS A REALLY STRONG
COLLECTION OF DEDICATED
CLINICIANS AND SCIENTISTS WHO
PROMOTE THESE RESEARCH
PORTFOLIOS AND THE SCIENCE AND
DATABASE DECISION-MAKING TO
BRING THESE CONCEPTS FROM THE
BENCH TO THE CLINIC.
THANK YOU ALL.
SO NOW I'LL TALK ABOUT THE U.S.
GOVERNMENT COVID-19 [INAUDIBLE].
DR. DIEFFENBACH GAVE A BEAUTIFUL
OVERVIEW OF THIS SLIDE.
THIS REPRESENTS THE OPERATION
WARP SPEED SUITE OF VACCINES
THAT WERE DEVELOPED UNDER THE
USG WITH THE EXCEPTION OF THE
PFIZER BIONTECH, WE DID NOT PLAY
MUCH OF A ROLE.
BUT I WANT TO DRAW YOUR
ATTENTION TO THE FACT THAT THERE
WERE REALLY THREE MAJOR PLATFORM
TYPES THAT WE USED.
THERE WAS THE NUCLEIC ACID WITH
THE MRNAs, THE VIRAL VECTORS,
IN PARTICULAR HERE THE
ADENOVIRUSES AND -- FORTUNATELY
THESE LED TO HIGHLY EFFICACIOUS
VACCINES WITH REGULATORY
SUBMISSIONS, EMERGENCY USE
AUTHORIZATIONS, LICENSURE -- IN
THE FIGHT AGAINST COVID-19.
PERHAPS ONE OF THE KEY LESSONS,
THOUGH, THAT WE'VE LEARNED FROM
THIS USG COVID RESPONSE IS THE
POWER OF LEVERAGING NIAID'S
ASSETS.
AN EXAMPLE, A REALLY GOOD
EXAMPLE OF ONE OF NIAID'S ASSETS
IS THE COLLECTIVE POWER AND
EFFORT OF OUR CLINICAL TRIAL
NETWORKS.
AND DR. DIEFFENBACH DESCRIBED
THE COVID-19 PREVENTION NETWORK
OR THE COVPN, AND THIS WAS A
GROUP OF ENORMOUSLY TALENTED AND
DEDICATED RESEARCHERS FROM THE
ACGG, BASICALLY THE NIAID-FUNDED
CLINICAL TRIAL NETWORKS CAME
TOGETHER AND PULLED OFF ALL
THESE STUDIES AND CONTRIBUTED IN
A MAJOR WAY.
THE STUDY STARTED IN JULY OF
2020, AND YOU CAN SEE ALONG THE
BOTTOM ROW THEY STILL CONTINUE
AT THIS TIME IN FOLLOW-UP.
THESE WERE EXTREMELY LARGE
STUDY, ON AVERAGE ABOUT 30,000
PARTICIPANTS IN EACH STUDY, AND
WE KNOW ALL THE INVESTMENTS IN
THE NIAID CLINICAL STRUCTURE --
WERE LEVERAGED TO MAKE THESE
TRIALS A SUCCESS.
WE CURRENTLY HAVE FOUR OF THESE
VACCINES AVAILABLE IN THE U.S.
MANY ARE AVAILABLE GLOBALLY.
ABOUT 230 MILLION PEOPLE HAVE
COMPLETED THEIR PRIMARY SERIES
IN THE U.S. AND OVER 50 MILLION
HAVE RECEIVED -- VACCINE
ENTERPRISE FOR THE COVID -- NEXT
SLIDE -- FOR THE COVID VACCINE
RESEARCH.
SO AGAIN WE ACKNOWLEDGE THAT THE
HIV VACCINE RESEARCH ENTERPRISE
PLAYED A VERY FAVORABLE ROLE IN
THE SUCCESS OF THE COVID
RESPONSE, MANY FOLKS HAVE SAID
THAT TODAY, AND I'D JUST SECOND
THAT.
WE RELIED ON PUBLIC-PRIVATE
PARTNERSHIPS AS WE'RE FAMILIAR
WITH USING AT LEAST IN OUR
PROGRAM, AND WE UNDERSTOOD THE
IMPORTANCE OF TRUST AND
TRANSPARENCY.
WE'VE ALL BEEN WORKING IN THE
HIV VACCINE FIELD AND WE KNOW
HOW IMPORTANT THAT IS TO ENGAGE
COMMUNITIES OR RETAIN THEIR
PARTICIPATION.
WE ALSO -- I'LL DRAW CONCLUSION
IN HOW POWERFUL THAT WAS TO
LEVEL THE PLAYING FIELD WHICH
ENABLES POWER SHARING AND TO
MAKE DECISIONS AND THE CLINICAL
TRIAL INFRASTRUCTURE WAS JUST
INVALUABLE.
ALL OF OUR NETWORKS, WE HAVE A
GLOBAL FOOTPRINT, AND THESE
RESEARCH SITES AND INVESTIGATORS
WERE ABLE TO PIVOT ON A DIME TO
BE ABLE TO USE THEIR EXPERTISE
IN DEVELOPING THESE VACCINES.
AND FINALLY, WE SEE THIS
SPILLOVER EFFECT WHICH MANY HAVE
TALKED ABOUT THIS -- YEAR
INVESTMENT IN BASIC SCIENCE AND
SOME OF THE CONTRIBUTIONS THAT
FACILITATE COVID COVID-19 VACCIE
RESPONSES, FOR EXAMPLE -- WHERE
HE KNEW FROM WORKING ON RSV AND
HIV THAT YOU NEEDED TO STABILIZE
THE TRIMERIC ENVELOPE, THE
SPIKE, AND SO FIVE OUT OF SIX
VACCINES FROM OPERATION WARP
SPEED ACTUALLY USED THAT EXACT
SUP THAT BARNEY DEVELOPED.
WE USE STANDARDIZED, VALIDATED
IMMUNE ASSAYS, WE PROMOTED DATA
SHARING AND OF COURSE WE WERE
ABLE TO CONTRIBUTE TO THE
IDENTIFICATION OF CORRELATES OF
PROTECTION IN ALL FIVE OF THESE
STUDIES.
SO WITH THINK WE'RE WELL
POSITIONED TO ADAPT AND IMPROVE
ON THE COVID-19 EXPERIENCE.
HERE I WANTED TO DRILL DOWN A
LITTLE BIT ON WHAT DIDN'T GO SO
WELL AND WHERE WE CAN IMPROVE.
SOME OF THESE WERE MENTIONED IN
THE PREVIOUS SLIDE, PUBLIC
PRIVATE PARTNERSHIPS.
HERE WITH VACCINE, WE USE
SEPARATE -- WAS A SEPARATE
PROTOCOL.
RUN BY A DIFFERENT SPONSOR.
BUT THEY WERE HARMONIZED.
WE USED SIMILAR TRIAL ELEMENT,
WE USED SIMILAR END POINTS, WE
USED SINGLE DSMB TO ANALYZE ALL
THE IMMUNE RESPONSES, AND THOSE
SAME LABS WERE ABLE TO DEVELOP
THE IMMUNE CORRELATES OF
PROTECTION.
I'D LIKE TO CALL OUT ONE
INVESTIGATOR IN PARTICULAR,
THAT'S DR. DAVID MONTEFURE WHO
REPURPOSED HIS HIV PSEUDOVIRUS
NEUTRALIZATION ASSAY TO BECOME A
VAL -- WHICH WAS THEN USED TO,
IN FACT -- FOR REG L REGULATORSE
DEES KATE -- AS A RESULT AND
ALSO TO HELP US APPROVE A
BIVALENT VACCINE ON THE BASIS OF
THAT NEUTRALIZATION ASSAY.
SOME OF THE AREAS WHERE WE CAN
IMPROVE, WE DEFINITELY NEED TO
ACCELERATE PANDEMIC RESPONSE
FUNDING AND ITS DISTRIBUTION.
I THINK THAT'S A MESSAGE THAT'S
COME THROUGH LOUD AND CLEAR
TODAY.
WE THINK WE SHOULD MAINTAIN A
CORE PANDEMIC RESPONSE STAFF.
WE NEED TO KEEP READY THE GLOBAL
CLINICAL TRIAL SITE CAPACITY,
MAINTAIN A CLINICAL TRIAL
REGISTRY, AND WE NEED TO
ESTABLISH METRICS FOR DIVERSITY
IN ENROLLMENT RIGHT UP FRONT.
WE CAN EXPEDITE IRB PRIORITY
REVIEWS, BIOSPECIMEN AND DATA
OWNOWNERSHIP AND ENSURE NIAID
CLINICAL RESEARCH IS CARRIED ON
POST EUA.
THERE'S A LOT OF QUESTIONS THAT
REMAIN AFTER THESE VACCINES WERE
AUTHORIZED AND WE NEED TO MAKE
SURE THAT NIAID HAS ACCESS AND
INVESTIGATORS HAVE ACCESS TO
CONTINUE THAT STUDY.
THE FINAL SLIDE I WILL PRESENT
HERE ON COVPN IN NATURE 2022,
THEY HAD A REVIEW ARTICLE WHERE
THEY LISTED 11 CLINICAL TRIALS
THAT WILL SHAPE MEDICINE IN
2023.
AT LEAST ACCORDING TO NATURE
MEDICINE.
WHAT'S REALLY -- HAPPEN TO BE
LISTED AS ONE OF OF THOSE THOSEE
THINK THAT'S ONE OF THE CLINICAL
TRIALS TO WAMP IN WATCH IN THER
2023.
THIS IS A STUDY DONE IN
SUB-SAHARAN AFRICA IN SEVEN
DIFFERENT COUNTRIES IN PEOPLE
WITH HIV W WHO ARE LARGELY
UNDERREPRESENTED.
IT'S THE LARGEST PHASE
3 EFFICACY TRIAL USING MRNA
VACCINES.
WE ARE LOOKING AT THESE AS
IMMUNOCOMPROMISED PEOPLE WHO
KNEED THEIR PRIMARY SERIES TO BE
AT A HIGHER DOSE,
100-MICROGRAMS, LOOKING AT TWO
DOSE VERSUS THREE DOSE RE
REGIMEN -- WHETHER THEY WERE
NAIVE OR PRIOR INFECTION AND WE
COULD LOOK AT THE IMPACT OF
HYBRID IMMUNITY IN THIS
POPULATION.
IMPORTANTLY WE'RE LOOKING FOR
PERSISTENT VIRAL SHEDDERS TO SEE
IF THERE WERE MUTATIONS
HAPPENING IN THESE INDIVIDUALS
TO SEE HOW THEY COULD INFORM
NEXT STEPS AND THEN WE WERE
LUCKY ENOUGH TO BE ABLE TO GET
ACCESS TO THE BIVALENT
BA.4/5 BOOSTER SO WE WERE ABLE
TO COMPARE THE MONOVALENT, THE
ORIGINAL MODERNA VACCINE WITH
THE BIVALENT.
SO I HOPE TO UPDATE THE COUNCIL
NEXT ON THE RESULTS OF THIS
STUDY.
HERE I'LL TALK ABOUT OUR HIV
VACCINE STRATEGY WHICH REALLY
FOCUSES ON DISCOVERY -- ANIMAL
WORK.
FIRST I'LL GIVE YOU -- THIS IS A
SLIDE YOU'VE SEEN MANY TIMES
BEFORE -- THE NIH VACCINE
STRATEGY.
WE HAD AN EMPIRICAL APPROACH AND
THERE ARE MANY STUDIES LIKE THE
702, 705 AND MOST RECENTLY NOW
THE MOSAICA STOPPED FOR
NON-EFFICACY -- INTO OUR
EFFICACY.
IT'S REALLY DISAPPOINTING FOR
THAT MOSAICO RESULT AND IT'S
ALSO SHOWING JUST UNACCEPTABLY
HIGH INCIDENCE LEVELS IN ANOTHER
HIGH RISK POPULATION.
WE CONTINUE IN PARALLEL, OF
COURSE, TO HAVE OTHER APPROACHES
FOR VACCINE DEVELOPMENT AND KNOW
THAT WE'RE GOING TO NEED ALL
HANDS ON DECK.
WE'RE GOING TO NEED UPTAKE OF
OTHER PREVENTIVE MEASURES AND
WE'RE GOING TO NEED NEUTRALIZING
ANTIBODIES AND CELLULAR IMMUNE
RESPONSES TO HELP US GET A GRIP
ON THIS PANDEMIC.
WHAT I'LL TALK ABOUT TODAY ARE
BASICALLY VACCINES TO ELICIT
BNABs SO THE ACTIVE APPROACH
FOR PREVENTION AND THEN I'LL
TALK A LITTLE BIT ABOUT PASSIVE
IMMUNOPROPHYLAXIS WITH BNABs.
BNABs ARE REALLY SORT OF A
CRITICAL COB IN VACCINE
DEVELOPMENT BECAUSE THEY HELP US
DESIGN THE IMMUNOGENS.
SO JUST TO FRAME THE DISCUSSION
IN THE CASE FOR BNABs, THERE
IS A GROWING BODY OF DAY THAT
SUPPORTS THE GROWING FEASIBILITY
OF -- THEY DEVELOP IN ABOUT 20%
OF PEOPLE WITH HIV -- HIGHLY
SPECIALIZED ALBEIT SLOWLY
DEVELOPED ANTIBODY.
THERE ARE MULTIPLE
NEUTRALIZATION TARGETS SO
THERE'S MULTIPLE SITES OF
WEAKNESS ON THE ENVELOPE AND
THAT'S WHERE THESE BNABs ARE
DIRECTED.
THE ENVELOPE CO-EVOLUTION
PROCESS BEING DEVELOPED IN
HUMANS IS FAITHFULLY
RECAPITULATED IN THE NON-HUMAN
PRIMATE MODEL, WHICH IS AN
EXCELLENT SOURCE -- LABORATORY.
WE KNOW FOR DECADES NOW THAT B
BNABs PREVENT INFECTION IN
NON-HUMAN PRIMARY CHALLENGE
MODEL.
BUT ONLY RECENTLY DID WE LEARN
THAT BNABs, AT LEAST THE --
CAN PREVENT HIV INFECTION IN
HUMANS WHEN WE CONDUCTED THE
ANTIBODY-MEDIATED PROTECTION
STUDY.
WHAT WE LEARNED THERE WAS THAT
THE ANTIBODIES IN HIGH ENOUGH
LEVEL AND THE INCOMING VIRUS IS
SENSITIVE THAT WE CAN ACTUALLY
MITIGATE ACQUISITION.
NOW ONE OF THE MORE -- MOST
EXCITING RECENT FINDINGS IS THAT
WE ARE LEARNING HOW TO IN A
PREDICTABLE WAY STIMULATE THE
HUMAN IMMUNE RESPONSE TO
ACTIVATE HIV BROADLY
NEUTRALIZING AND BODY PRECURSORS
THROUGH GERMLINE AND TARGETING
VACCINATION.
ONE BIG OPEN REMAINING QUESTION
TO BE INTELLECTUALLY HONEST AND
TECHNICALLY HONEST IS THAT WE
DON'T KNOW WHETHER THE VACCINES
CAN DRIVE BROAD NEUTRALIZING
ANTIBODIES IN HIGH ENOUGH TITERS
TO PROTECT SO WE HAVE TO RELY ON
OTHER PARTS OF THE IMMUNE SYSTEM
AS I SAID BEFORE.
THIS IS AN OVERVIEW OF WHAT WE
USE CALLED ANTIBODY BASE VACCINE
DESIGN.
SO WE START WITH AN ANTIBODY
NEUTRALIZING -- SAY FOR EXAMPLE
THE CD4 BINDING SITE OR THE
B3 SUPER SITE.
WE IDENTIFY THE VIRAL EPITOPE
THAT'S TARGETED BY THAT SPACING
AT THE ATOMIC LEVEL AND THEN USE
THIS DESIGN APPROACH TO MODEL
OUR VACCINE.
THAT VACCINE SHOULD SIMILARLY
ELICIT A NEUTRALIZING AN BODY.
NOW, THE ISSUE WITH THESE
IMMUNOGENS THAT ARE DESIGNED --
THERE ARE DEFINITELY -- THEY
TEND TO BE SUBDOMINANT ON THE
TRIMERIC SPIKE, AND THEY ARE
HARD TO ACCESS.
THERE'S GLYCAN COVERAGE AS YOU
KNOW SO IT'S NOT EXACTLY
STRAIGHTFORWARD BUT I'D LOVE TO
SHOW YOU SOME PROGRESS WE HAVE
IN THIS AREA.
WE NOW KNOW WE NEED TO TARGET
GERMLINE.
SO THIS IS JUST A GRAPHIC THAT
SHOWS HOW WE WOULD INDUCE THESE
BNABs AT VACCINATION, AGAIN
YOU SEE THE MULTIPLE SITES OF
VULNERABILITY.
WE USE MULTIPLE DIFFERENT
BNABs THAT ARE LISTED BELOW
THOSE SITES TO DEVELOP OUR IMAGE
AND DESIGN AS BNAB TARGETS.
WE PRIME THE IMMUNE SYSTEM
TARGETING NAIVE B CELLS.
THOSE NAIVE B CELLS HAD TO GO TO
THE GYM, WHERE THEY WORK OUT AND
THE LONGER THEY'RE IN THE GYM,
THE BETTER THEY BECOME.
THEY NEED TO RECYCLE THROUGH THE
JENSEN TER, THEY NEED T
FOLLICULAR HELP AND THROUGH
SEQUENTIAL IMMUNIZATION WE THINK
WE CAN BOOST THESE INTO MATURE B
CELLS THAT CAN ELICIT BNABS.
SO BOTTOM LINE IS THE OBJECTIVE
TO DRIVE B CELLS -- WE KNOW
PRECURSORS ARE RARE, THEY'RE
DIVERSE AND DIFFICULT TO
ACTIVATE WITH HIV PROTEINS.
SO WHAT THE INVESTIGATORS HAD TO
DO IS DEVELOP THESE SPECIALIZED
GENERAL TARGETING IMMUNOGENS
WITH OPTIMAL AFFINITY THAT CAN
BROADLY TARGET A DIVERSE
PRECURSOR POOL OF B CELLS WITHIN
A BNAB CLASS.
I CAN SHOW YOU MORE DETAIL ON
THIS STRATEGY.
WE THINK WE NEED SEQUENTIAL
IMMUNIZATION TO INDUCE THESE
BNABs.
SO IF YOU LOOK ON THE FAR LEFT,
THE VACCINE PRIME WITH GERMLINE
TARGETING, WE'D ACTUALLY
ACCOMPLISH THAT STEP.
THIS WAS DONE IN THE PHASE ONE
G001 STUDY THAT WAS PUBLISHED
THIS YEAR AND I'LL TALK ABOUT
THAT IN DETAIL IN THE NEXT
SLIDE.
BUT SINCE WE'VE ACCOMPLISHED
THAT FIRST STEP, NOW WE'RE GOING
TO BE MOVING INTO BOOSTING.
SO HERE'S THE -- GIVEN THE
SIGNIFICANCE OF IT I WANTED TO
REVIEW SOME OF THE DATA.
THIS IS A SELF ASSEMBLING
NANOPARTICLE, USED WITH A STRONG
EDGE -- MANY ARE FAMILIAR HOW --
ADJUVANT IS.
THE STUDY WAS SUCCESSFUL IN THAT
97% OF PARTICIPANTS DEVELOPED
VRC-OH 1 CLASS IGG POSITIVE B
CELLS AND THEY WERE IN HIGH
ENOUGH FREAK SE FREQUENCY TO COR
BOOSTING.
DOSE BNAB RESPONSES WERE
ELICITED AT HIGH AFFINITIES TO
THE -- AND THEY INCREASED OVER
TIME.
SO WE THINK THE SIGNIFICANCE OF
THE STUDY IS IT VALIDATED THE
GERMLINE TARGETING CONCEPT AND
SERVES AS A CANDIDATE TO PRIME
BVRC018 ANTIBODIES.
PROVIDES KEY REAGENT FOR US TO
STUDY THIS PROCESS MOVING
FORWARD.
THE NEXT STEPS OF COURSE ARE TO
USE MRNA DELIVERY ALONG WITH A
CORE BOOST, AGAIN, MRNA DELIVERY
TO ACCELERATE.
JUST LIKE TO REMIND YOU THAT
WE'VE COME A LONG WAY WITH
MRNAs, NOT ONLY ARE EXCELLENT
PROTEIN PROTEIN PRODUCTION
FACILITY, THEY CAN ENCODE VERY
COMPLEX HIV IMMUNOGENS THAT ARE
GOING TO BE NEEDED FOR HIV
VACCINE.
THIS STUDY THAT COMES OUT OF --
SHOWS HIV EXPRESSED ENVELOPE
NANOPARTICLES ARE WELL FOLDED
WITH OPTIMIZED MUTATIONS.
THEY ARE STABLY EXPRESSED AND SO
PREFERENTIAL B CELL BINDING AND
IN AN ANIMAL MOUSE MODEL, THEY
SHOWED THAT THEY COULD ELICIT
AUTOLOGOUS TIER 2 NEUTRALIZING
ANTIBODIES WITH IMPORTANT BNAB
MUTATIONS THAT WE THINK IS A
VERY PROMISING ANIMAL MODEL AND
MAY PREDICT WHAT WE CAN SEE IN
HUMANS.
HERE IS WHERE I'M GOING TO
PROCEED WITH SEVERAL NON-HUMAN
PRIMATE STUDIES, SOME OF WHICH
YOU'LL BE FAMILIAR WITH.
THIS PAPER WAS PUBLISHED IN
NOVEMBER 2022 IN NATURE, OR
SEPTEMBER, I THINK, 2022.
IT MIGHT BE FAMILIAR BECAUSE I
REVIEWED IT LAST YEAR PRIOR TO
PUBLICATION, BUT IT'S SO ELEGANT
AND IT'S SO SIMPLE, I THINK IT
REALLY BEARS REPEATING AND
EMPHASIZING SOME OF THE
FINDINGS.
WHAT THEY DID WAS THEY JUST
TOOK -- COMPARED THE BOLUS
INJECTION OF AN IMMUNOGEN,
WHAT'S CALLED AN MD30.3, WHICH
IS A TRIMER PROTEIN, AND WAS
ADJUVANTED WITH A POTENT
ADJUVANT AND THEY COMPARED A
BOLUS SINGLE INJECTION VERSUS
GIVING SMALLER DOSES EVERY OTHER
DAY OVER A 12-DAY PERIOD WHICH
THEY CALL SLOW PRIMING WHA. THEY
FOUND WAS THERE WERE DRAMATIC
INCREASES IN THE LENGTH OF THESE
GERMINAL CENTER RESPONSES.
THEY SEEMED TO BE PROLONGED OVER
A SIX-MONTH PEERPD, THERE WAS
CONTINUOUS GERM CELL ACTIVITY,
AND IMPORTANTLY AS BOXED IN THE
MID EVIDENTLY THIS SLIDE, YOU
SEE THERE'S -- THERE WAS TIER
2 NEUTRALIZATION -- WHICH HAS
REALLY BEEN A BIG, BIG STEP WE
NEEDED TO SEE IN OUR ANIMAL
MODEL.
THE LAST THING I WANTED TO
MENTION WAS THAT THROUGH THE
POWER OF CRYO-EM -- A WAY TO
CHARACTERIZE B CELL RESPONSES,
YOU CAN SEE ON THE LEFT THEY
SHOW ACTUALLY ON THE -- WHERE
THESE BARRIERS TO ANTIBODY
RESPONSES ARE BINDING, AND YOU
CAN TELL THAT THEY'RE HITTING A
LOT OF DIFFERENT EPITOPES.
THEY'RE HITTING THE B1, YOU
KNOW, THEY'RE HITTING THE --
THEY'RE HITTING VARIOUS SITES
AND THAT SHOWS US THAT WITH THE
RIGHT DELIVERY AND WITH THE
RIGHT ADJUVANT, WE CAN
AFFINITY-MATURE THE ANTIBODY
RESPONSE AND GET BREADTH AND
INCREASED PROPENSITY.
OKAY.
NEXT SLIDE.
THIS IS JUST REINFORCING THE
IDEA THAT AGAIN IN THE NON-HUMAN
PRIMATE MODEL, WE CAN TAKE
ANOTHER TRIMER THAT WAS
FORMULATED WITH A POTENT
ADJUVANT 30152 -- PROTECTION
TO --.
THIS IS WHERE I'M GOING TO MOVE
NOW FROM THE ANTIBODY BASE OF
VACCINES TO -- WHICH MANY OF YOU
ARE FAMILIAR WITH THE LEWIS --
THAT HAS BEEN SHOWN THROUGH THE
INDUCTION OF VERY SPECIALIZED
T-CELLS THAT ARE PRIMED WITH THE
CMV VACCINE THAT CAN CONTROL SIV
REPLICATION AND IS SAID TO CLEAR
INFECTION IN ABOUT 50 TO 60% OF
THE ANIMALS.
THIS HAS BEEN REPEATED IN OVER
200 ANIMALS.
IT'S BEEN SHOWN NOW, THE
IMPORTANCE OF THIS STUDY, THAT
THEY CAN SHOW IT IN NOT ONLY THE
RHESUS MACAQUE BUT ALSO IN THE
SIN MOL GUS SPECIES.
THIS IS IMPORTANT BECAUSE CMV IS
VERY SPECIES-SPECIFIC AND IT
WASN'T CLEAR IF THIS WAS GOING
TO BE A ONE OFF IN RHESUS BUT
NOW WHAT THEY'VE SHOWN IS AS
LONG AS THE VECTOR MATCHES THE
CYNOS, IT WILL INDUCE THE SAME
RESPONSE -- IT ELICITS THE SAME
PROTECTION AND ALSO THE SAME
SIGNATURE THAT'S ASSOCIATED WITH
PROTECTION.
SO THIS IS REALLY IMPORTANT
BECAUSE IT'S POSSIBLE THAT -- IF
WE USE THE HUMAN [INAUDIBLE].
ON THIS SAME VECTOR, THE SAME
CMV VECTOR, WE'VE FOCUSED ON
THESE RESTRICTED T-CELLS BECAUSE
WE SUSPECTED THEY WERE
RESPONSIBLE FOR PROTECTION AND
WE FOUND OUT INTERESTINGLY
ENOUGH THAT THEY HAVE MYELOID
CELL TROPISM.
THEY TARGET THE MYELOID CELLS
AND THAT ENABLES THEM TO INDUCE
THESE MHC RESTRICTED T-CELLS
THAT CAN CONSTRAIN SIV
REPLICATION SO THE KEY FINDING
HERE IS THAT ONLY VECTORS THAT
ARE PROGRAMMED TO ELICIT THESE
MHC-E RESTRICTED CD8 T-CELLS CAN
PROTECT AGAINST -- TRANSMISSION
TO THE HUMAN HIV MODEL.
THIS COULD BE FAMILIAR TOO
BECAUSE I PRESENTED IT LAST
TIME.
THANKS SO MUCH FOR THAT, KEN.
I REALLY APPRECIATE THIS.
THIS IS BASICALLY A STUDY THAT
WILL LOOK FOR THE
REPRODUCIBILITY OF AN IMPORTANT
STUDY THAT CAME OUT OF EMORY IN
2020 THAT SHOWED THAT IF YOU USE
TRIMERIC PROTEIN ALONE OR WITH
VARIOUS VIRAL VECTORS, YOU CAN
ACTUALLY INDUCE BOTH THE T-CELL
AND AN ANTIBODY RESPONSE.
IT TURNS OUT THE COMBINATION OF
THAT RESPONSE LOWERS THE
THRESHOLD OF THE ANTIBODY LEVELS
THAT ARE NEEDED FOR PROTECTION
AND IT ALSO INCREASES
DURABILITY.
THESE ARE VERY IMPORTANT
QUESTIONS FOR VACCINE DESIGN.
[INAUDIBLE].
THANKS.
SO WE'RE FORTUNATE TO HAVE A
TRANSLATIONAL BRANCH THAT I TOLD
YOU IS FROM -- DOES MANY, MANY
THINGS IN ADDITION TO TMP
MANUFACTURING.
CAN YOU YOU CAN SEE ALL THE PROT
TYPES THEY WORK ON, VIRAL
VECTORS.
THE GOAL IS FOR THEM TO PRODUCE
THE BEST -- AND BE TRANSLATED
INTO CLINICAL TESTING THROUGH
PILOT -- PRODUCTION.
THIS IS A LIST OF ALL THE
ADJUVANTS THAT ARE NOW
AVAILABLE.
INVESTIGATORS FREQUENTLY HAVE
TROUBLE GETTING ACCESS TO
ADJUVANTS AND THIS MADE IT A
GOAL TO MAKE THESE EIGHT THAT
ARE PROMISING AND ON THE PATH TO
INVESTIGATORS.
SO CAN ONLY HIGHLIGHT FOUR HIV
VACCINE CLINICAL TRIALS.
THERE ARE MANY TRIALS GOING ON,
BUT IT'S IMPORTANT THAT YOU KNOW
THAT THERE ARE MULTIPLE RNA HIV
VACCINE -- IN CLINIC.
COMPARES MEMBRANE -- THIS WAS
THE SAME TRIMER THAT WAS REACHED
IN THAT PRIMATE STUDY.
THAT WILL NOW BE BOOSTED WITH AN
MRNA CORE IMMUNOGEN.
I WILL JUST GO OVER THERE REALLY
QUICKLY.
THERE ARE THREE PHASE ONE
STUDIES THAT CAN ELICIT
NEUTRALIZING ANTIBODIES.
SOME OF THESE ARE POLYCLONAL.
THEY USE PROTEINS WITH POTENT
ADJUVANTS LIKE 3M-052.
THEY INDUCE YOU A TOLL JUST TIER
2 NEUTRALIZING ANTIBODIES.
SPECIFICALLY WITH THAT ADJUVANT.
IT'S NOT SEEN WITH OTHER
ADJUVANTS JUST TO BRING THAT
OUT.
FINALLY WE SAW THIS WITH
HVTN300, AGAIN THAT SAME
ADJUVANT, AND FINALLY I WANTED
TO JUST BRING TO YOUR ATTENTION
THE HVTN133, WHICH IS AN MPER
PEPTIDE LIPOSOME WHICH INDUCES
LOW LEVELS OF HETEROLOGOUS
NEUTRALIZING ANTIBODIES.
IF YOU CAN SKIP THROUGH THE NEXT
THREE SLIDES REALLY QUICKLY.
I CAN WRAP THIS UP.
IT'S THE DATA SLIDE, YOU HAVE
THOSE IN YOUR DECK TO REVIEW,
NEUTRALIZING ANTIBODIES.
I WANTED TO GO TO THE NIAID HIV
ANTIBODY PORTFOLIO.
BY NIAID I MEAN THE VACCINE
RESEARCH CENTER AND THE DIVISION
OF AIDS.
THERE IS A TRIPLE ANTIBODY
COMBINATION THAT IS THOUGHT TO
BE THE MOST EFFECTIVE FOR
PREVENTION.
THIS INVOLVES AN ANTIBODIES AGAT
THE BINDING SITE -- POTENCY
BREADTH CURVES IN THE UPPER
RIGHT IN RED, YOU SEE THE TRIPLE
COMBINATION THAT WE'VE SELECTED
THAT SHOULD PROVIDE HIGH LEVELS
OF PROTECTION AGAINST BOTH --
VIRUSES.
JUST WANTED TO STATE THIS WAS
IMPORTANT THAT A PAPER FROM
PETER GILBERT THAT ESTABLISHED A
NEUTRALIZATION TITER BIOMARKER,
AN IMPORTANT TARGET FOR US, ID80
TITERS ARE PREDICTED TO OFFER
90% EFFICACY.
THESE ARE THE BNAB VACCINES IN
THE PIPELINE.
THIS IS THE FIRST IN HUMAN --
VACCIVACCINE THAT'S PLANNED THAT
SHOULD START THIS YEAR.
WE CONCEDE WE'LL LIKELY NEED
MULTICOMPONENT VACCINES TO
TARGET MULTIPLE NEUTRALIZATION
EPITOPES AND WILL PROBABLY NEED
THESE CELLULAR BASED VACCINES TO
COME IN AND HELP US REACH THE
GOAL OF AN HIV VACCINE TO HELP
END THE EPIDEMIC.
WE THINK AN HIV VACCINE REMAINS
ESSENTIAL TO CONTROL THE
EPIDEMIC.
THANK YOU VERY MUCH.
I APPRECIATE ANY EXTRA TIME AND
CAN TAKE QUESTIONS OR SAVE THEM
FOR LATER.
THANKS, KEN.
>>THANK YOU, DR. MAROVICH, THAT
WAS FANTASTIC, SO MUCH PROGRESS
AND IT PARTICULARLY EXCITING TO
SEE HOW MUCH OF THAT SCIENCE WAS
USED IN THE COVID VACCINES AND
NO DOUBT WILL BE IN THE
SUCCESSFUL -- TO BE COMING
SUCCESSFUL -- IN THE INTEREST OF
TIME IS HOLD QUESTIONS HERE
UNTIL WE DO HAVE SOME TIME AT
THE END IF THAT'S OKAY.
AND WE WILL CONTINUE WITH
DR. SHERYL ZWERSKI, PREVENTION
SCIENCES PROGRAM.
SO LET ME TURN IT OVER TO
DR. ZWERSKI.
>>OKAY.
CAN EVERYONE HEAR ME?
>>YES.
>>EXCELLENT.
GOOD AFTERNOON, EVERYONE.
THANK YOU VERY MUCH FOR THE
OPPORTUNITY TO TALK ABOUT THE
WORK OF THE PREVENTION SCIENCES
PROGRAM.
WHAT WE'VE DONE IN THE PAST YEAR
AND KIND OF THE WAYS FORWARD.
SO I'M GOING TO GO OVER A LITTLE
BIT OF BACKGROUND.
SOME ORIENTATION TO THE PROGRAM.
SOME OF OUR 2022 ACCOMPLISHMENT
HIGHLIGHTS.
KIND OF WHAT WE SEE AS COMING
NEXT, WHAT ARE THE CHALLENGES
AND OPPORTUNITIES ASSOCIATED
WITH THAT.
AND THEN OF COURSE TAKE ANY
QUESTIONS AS WE'RE ABLE.
OKAY?
SO A LOT OF THIS, YOU ALL KNOW
BUT I THINK FOR US IS WE THINK
ABOUT KIND OF WHAT IS NEXT IN
THE WAY FORWARD REALLY IMPORTANT
FOR US TO KEEP THESE THINGS, YOU
KNOW, THESE FACTS AND FIGURES IN
MIND, REALLY IMPORTANT PIECE IS
1.5 MILLION NEW INFECTIONS IN
2021.
AND THEN THIS IS WHAT WE'RE
LOOKING AT ON A D A DAILY BASIS.
SO ABOUT 430 CHILDREN UNDER THE
AGE OF 15 OF THE NEW INFECTIONS
PER DAY.
AND JUST AGAIN PROBABLY A KNOWN,
NO SURPRISE TO ANYONE HERE, THAT
WE'RE CERTAINLY NOT GOING TO
MEET OUR TARGET OR IT APPEARS
NOT, FOR THE 2025 DECREASE IN
NUMBER OF NEW INFECTIONS
GLOBALLY.
AND THEN A REMINDER TO US OF HOW
THE NEW INFECTIONS RIGHT DOWN BY
POPULATION.
MANY KEY POPULATIONS, OF COURSE,
IN SUB-SAHARAN AFRICA, A LOT OF
MORE GENERAL POPULATION, BUT
AGAIN CRITICAL FOR US TO THINK
OF AS WE THINK OF WHAT PRODUCTS,
WHAT CHOICES, WHAT
INTERVENTIONS, YOU KNOW, SHOULD
WE BE WORKING ON, SHOULD WE BE
TESTING NEXT.
AND AGAIN, HERE IS NUMBER OF
PEOPLE WHO RECEIVED PREP, AT
LEAST ONCE DURING THE REPORTING
PERIOD.
AND AS YOU CAN SEE, EVERYBODY,
EVERY SINGLE REGION HERE
REPORTING IS RELATIVELY FAR OFF.
INTERESTINGLY, IF YOU LOOK AT
EASTERN AND SOUTHERN AFRICA AND
WESTERN AND CENTRAL AFRICA, AS
FAR AS RELATIVE TO TARGETS,
THEY'RE GETTING CLOSE TO 50%,
STILL A FAR WAYS OFF, BUT IF WE
LOOK AT ASIA AND THE PACIFIC,
LATIN AMERICA, EVEN WESTERN AND
CENTRAL EUROPE AND INCLUDING
NORTH AMERICA, WE ARE EVEN
FURTHER OFF ON OUR TARGETS.
THIS IS REALLY SHOWING NEW
INFECTIONS IN CHILDREN AS
OPPOSED TO ANTIRETROVIRAL
COVERAGE AMONG PREGNANT WOMEN
GLOBALLY.
BETWEEN 2010 AS YOU CAN SEE HERE
AND AGAIN 21, IT'S IMPORTANT, OF
COURSE, TO US AS WE THINK ABOUT,
YOU KNOW, ADVANCING MA TEERNL
AND CHILD HIV TREATMENT.
AS YOU CAN SEE CERTAINLY THE
COVERAGE IN WOMEN ROSE FROM 2010
SIGNIFICANTLY, BEEN RELATIVELY
LEVEL OVER THE LAST SEVERAL
YEARS, AND THAT THE INFECTIONS
IN CHILDREN HAVE COME DOWN
SIGNIFICANTLY WHEN WE LOOK FROM
2010 TO WHERE WE ARE, BULL NOT
DRASTIC DIFFERENCES OVER THE
LAST COUPLE YEARS AND THE LAST
SEVERAL YEARS.
SO IMPORTANT FOR US AS WE THINK
ABOUT, YOU KNOW, WHAT WE NEED TO
DO IN THIS SPACE MOVING FORWARD.
SO THIS WAS A RECENT ARTICLE IN
THE "NEW YORK TIMES" ABOUT THE
GLOBAL PUSH TO TREAT HIV AND HOW
THAT IS -- HOW CHILDREN ARE
BEING LEFT BEHIND IN THAT
EFFORT.
IT'S REALLY A NUMBER OF
DIFFERENT REASONS, AND VARY SOME
OF COURSE FROM PLACE TO PLACE,
BUT ULTIMATELY RIGHT NOW WE'RE
AT THE POINT WHERE ABOUT 76% OF
ADULTS WHO NEED HIV TREATMENT
ARE ON TREATMENT, BUT ONLY ABOUT
50% FOR CHILDREN.
AS I SAID, A NUMBER OF REASONS.
OFTENTIMES CHILDREN ARE NOT
BEING FOUND AS FAR AS NEEDING OR
IDENTIFIED AS NEEDING HIV
TESTING.
SOMETIMES, YOU KNOW, TEST KIT
ARE OUT OF STOCK, OTHER TIMES
ANTIRETROVIRALS FOR CHILDREN,
THE FREE ANTIRETROVIRALS ARE OUT
OF STOCK.
OCCASIONALLY FOR MOTHERS AS
WELL.
AND AS WE ALL KNOW, THE COVID
PANDEMIC HAS NOT HELPED THIS
SITUATION AT ALL AND PROBABLY
SET US FURTHER BEHIND, SO
THINKING ABOUT OUR WORK AS TO
WHAT OUR PIECES IN THIS ARE,
WE'LL TALK ABOUT THIS A LITTLE
BIT MORE IN THE PRESENTATION
LATER, BUT ONE OF OUR MAJOR
FOCUSES IS GETTING THE OPTIMAL
TREATMENT, PROVING THEY'RE SAFE
AND EFFECTIVE, THE CORRECT
DOSING IN CHILDREN, AND IN
PREGNANT WOMEN, AND THEN THAT
LEAVES ALL THESE IMPLEMENTATION
ISSUES, WHICH ARE NOT SO MUCH
DIRECTLY NIAID, BUT I THINK
WE'LL TALK ABOUT KIND OF HOW WE
TRY AND THINK ABOUT PARTNERING
MAYBE SOMETIMES WITH
NON-TRADITIONAL PARTNERS ON
SPECIFIC SLICES OF
IMPLEMENTATION, BUT IMPORTANT
FOR US TO KEEP IN MIND.
SO I WANT TO INTRODUCE YOU ALL
TO THE PREVENTION SCIENCES
PROGRAM, A LITTLE BIT ABOUT THE
STAFF, WHAT CHANGES WE'VE HAD IN
THIS PAST YEAR.
I ALSO WANT TO, THOUGH,
ACKNOWLEDGE, IN ADDITION TO THE
EXTRAORDINARY WORK THAT ALL OF
THE STAFF IN PSP DO, IT TAKES
EVERY ONE OF US CONTRIBUTING TO
THE MISSION TO BE ABLE TO DO THE
WORK THAT WE'RE DOING, WE ALSO
PARTNER ACROSS ALL OF THE
SCIENTIFIC PROGRAMS, SO BASIC
SCIENCES, THERAPEUTIC SCIENCE,
VACCINE RESEARCH PROGRAM, BUT
FOR THE WORK THAT WE OFTEN DO,
WHICH ARE THE REGISTRATIONAL
STUDIES FOR PRODUCTS, WE ARE
VERY CLOSE -- WE WORK VERY
CLOSELY WITH BOTH OUR
COLLEAGUES, THERE'S NO WAY WE
COULD DO THIS WORK WITHOUT THEM,
AND THEN OF COURSE OFTENTIMES
IT'S MORPHED ACROSS INSTITUTES,
PARTICULARLY WITH NIMH, NICHD,
OAR AND OTHERS, AND AS WELL AS
PHARMA PARTNERS AND OTHER
PARTNERS THAT ARE CRITICAL TO
THE WORK THAT WE DO.
SO JUST A LITTLE BIT OF
ORIENTATION HERE AND I'LL POINT
OUT THE CHANGES WE'VE HAD IN THE
LAST YEAR.
WE ARE IS THE HAVE THE FOUR BRL
AND THEN KIND OF THE FUNCTIONAL
GROUPS THERE WITHIN THE OFFICE
OF THE DIRECTOR.
THE ADMINISTRATIVE GROUP, AND
THEN THE REGISTRATIONAL TRIALS
AND COLLABORATIVE PARTNERSHIPS
GROUP THAT REALLY WORK ON
MANAGING ALL OF THE -- BACK,
PLEASE -- ALL OF THE
REQUIREMENTS THAT WE NEED TO
MEET FOR OUR REGISTRATIONAL
TRIALS AND REALLY TAKING A
PROJECT MANAGEMENT SORT OF
APPROACH THERE.
OUR FOUR BRANCHES, THE
PRE-CLINICAL MICROBICIDE AND
PREVENTION RESEARCH BRANCH,
DR. LESLIE MARSHAL WENT TO OAR
AS MANY OF YOU KNOW, AND -- WE
HIRED DR. B ARC RNA DAY AS A
PROGRAM OFFICER IN THIS GROUP
AND WE'RE VERY PLEASED THAT
SHE'S JOINED US.
OUR CLINICAL MICROBICIDE
RESEARCH BRANCH HAS STAYED THE
SAME.
THE CLINICAL PREVENTION RESEARCH
BRANCH, THE BRANCH CHIEF IS IN
THE COMMISSION CORPS AND WOUND
UP TAKING A POSITION AT THE
EMBASSY IN NIGERIA TO REALLY
CONTRIBUTE THERE.
SO I'VE BEEN THE ACTING BRANCH
CHIEF FOR THE LAST SIX MONTHS
FOR THIS GROUP.
LYDIA SOTO-TORRES CONTINUES TO
SERVE AS THE DEPUTY, AND WE HAVE
HIRED DR. JAMAL DEJLI AS A NEW
PROGRAM OFFICER IN THIS BRANCH
AND WE'RE VERY PLEASED THAT HE
IS THERE.
IN THE MATERNAL ADOLESCENT AND
PEDIATRIC RESEARCH BRANCH, WE
HAVE RECENTLY GAINED
DR. CHRISTINE CHIOU, SERVING AS
PROGRAM OFFICER, A MEDICAL
OFFICER AND ALSO HAS PROJECT
OFFICER OR CORE CERTIFICATIONS,
SO WE'RE REALLY THRILLED FOR HER
ADDITION ALSO.
JUST A REMINDER, YOU ALL HAVE
SEEN THIS BEFORE, OUR REALLY
HIGH LEVEL OBJECTIVES HAVE NOT
CHANGED.
JUST AS A REMINDER, DEVELOPMENT
OF HIV PREVENTION PROJECTS,
FURTHER UNDERSTANDING THE
BIOLOGY OF HIV SUSCEPTIBILITY,
AND THEN WORKING WITH PARTNERS
ON IMPROVING ENGAGEMENT OF KEY
POPULATIONS.
AS WE MOVE TO THE MATERNAL CHILD
PRIORITIES, REALLY IMPROVING HIV
TREATMENT AND PREVENTION IN
PREGNANT WOMEN AND CHILDREN, AND
THEN OPTIMIZING STRATEGIES TO
DIAGNOSE, TREAT AND PREVENT TB
IN BOTH THE MATERNAL AND
PEDIATRIC POPULATIONS, AND THEN
CONTRIBUTING TO AND EVOLVING THE
HIV-FREE REMISSION OR CURE
RESEARCH AGENDA IN INFANTS AND
CHILDREN.
SO THIS IS A LISTING OF OUR
CURRENT PSP PROGRAMS.
OF COURSE IN ADDITION TO THESE
PROGRAMS, WE HAVE A NUMBER OF
INVESTIGATOR-INITIATED GRANTS
THAT ALSO, OF COURSE, CONTRIBUTE
TO THE MISSION OF THE PROGRAM.
JUST TO ORIENT YOU HERE A
LITTLE, YOU CAN SEE ALONG THE
BOTTOM, WE HAVE THE PRODUCT
DEVELOPMENT OR AXIS THERE
STARTING SOME OF OUR WORK IN
DISCOVERY GOING ALL THE WAY
THROUGH PRE-CLINICAL,
TRANSLATIONAL, PRE-PHASE ONE,
AND THEN ALL THE WAY THROUGH
PHASE ONE, TWO AND THREE IN THE
LATER CLINICAL TESTING.
JUST TO ORIENT YOU A BIT, THE
COLOR SCHEME THERE, THE LIGHTER
GREEN IS MORE MATERNAL PEDIATRIC
FOCUSED, THE DARKER GREEN MORE
ADULT ADOLESCENT AND ADULT HIV
PREVENTION FOCUSED, AND AS YOU
CAN SEE, SOME OF THESE PROGRAMS
AND INITIATIVES ARE BOTH.
HAVE A FOCUS IN BOTH AREAS.
AT THE BOTTOM ARE WHAT WE'VE
CALLED OUR CRIMP CONTRIBUTE,
WHICH GOES THROUGH FY 2023, AND
THEN OF COURSE TAKING OVER ON
THE NEXT ITERATION WILL BE OUR
RAPPS CONTRACT, REALLY SERVE AS
A BASIS AND AS A PLATFORM, IF
YOU WILL, GAP-FILLING SERVICES
AS WE MOVE ALONG FROM THE
PRE-CLINICAL THROUGH THE LATER
CLINICAL TESTING STAGES, AND
THEN OTHERS OF THESE ARE VERY
SPECIFICALLY FOCUSED AND THEN WE
HAVE THE TWO NETWORKS, THE HTPTN
AND THE IMPACT NETWORK THAT A
LOT OF THIS WORK, WHEN IT GETS
TRANSLATED INTO CLINICAL
TESTING, THAT'S WHERE WE MOVE
TO.
SO I WANT TO TAKE A MOMENT AND
GO OVER SOME 2022 ACCOMPLISHMENT
HIGHLIGHTS.
THIS IS BY NO MEANS AN
ALL-INCLUSIVE LIST.
IT'S BEEN A REALLY PRODUCTIVE
YEAR AND THESE ARE JUST SOME
HIGH LEVEL HIGHLIGHTS.
SO STARTING IN THE AREA OF
DEVELOPMENT OF HIV PREVENTION
PRODUCTS IN THE PAST YEAR, THE
SOUTH AFRICA, ZIMBABWE AND
AUSTRALIAN REGULATORY
AUTHORITIES HAVE APPROVED
CABOTEGRAVIR LONG-ACTING FOR
PREP IN INDIVIDUALS FROM
35 KILOGRAMS AND ABOVE, AND
THOSE WERE BASED OF COURSE ON
THE HPTN 083 AND 084 STUDIES.
WE'VE CONTINUED OUR ONGOING
SAFETY AND PK TRIALS OF
MONOCLONAL ANTIBODY
COMBINATIONS.
THIS IS WORK THAT WE DO VERY
MUCH IN COLLABORATION WITH OUR
VRP COLLEAGUES AS WELL AS IT'S A
COLLABORATION BETWEEN TWO
NETWORKS, THE HVTN AND THE HPTN.
THERE WAS ALSO THE COMPLETION OF
THE PRIMARY ANALYSIS OF MTN-043,
WHICH IS THE DAPIVIRINE RING IN
LACTATING MOTHER AND
MOTHER-INFANT PAIRS, THEIR
INFANTS ARE FOLLOWED, AND THAT
INFORMATION WILL BE PRESENTED AT
C ROI NEXT MONTH.
THEN CONTINUING ALONG WITH OUR
PRODUCT DEVELOPMENT AND OUR
FOCUS ON PEDIATRICS, AS I JUST
MENTIONED, OUR RAPP SRT WHICH
YOU ALL ARE AWARE OF, OF COURSE
THAT CONCEPT WAS BROUGHT TO YOU,
GOSH, PROBABLY A YEAR OR YEAR
AND A HALF AGO OR SO, WE HAD THE
RELEASE OF THE RFP IN MARCH,
THEN RECEIVED PROPOSALS IN THE
SUMMER, AND THEN HAD REVIEWS IN
THE FALL AND WE'RE ON TARGET TO
MAKE THE AWARDS IN SUMMER OF
THIS YEAR.
SO WE'RE VERY EXCITED ABOUT THIS
NEXT ITERATION OF THE
GAP-FILLING CONTRACT.
AND THEN WE'VE ALSO ESTABLISHED
COLLABORATIONS WITH WORLDWIDE
STAKEHOLDERS IN THE AREA OF
PEDIATRIC FORMULATION, PARTLY AS
AN OUTGROWTH OF RAPPS.
I APOLOGIZE FOR ALL OF THESE
ACRONYMS HERE.
THERE'S NO WAY THAT I WOULD HAVE
HAD ENOUGH ROOM TO EVER WRITE
THEM ON A SLIDE, SO -- AND MANY
OF YOU PROBABLY ALREADY KNOW
THESE, BUT JUST TO GO THROUGH A
COUPLE OF THEM, THE GAP-F STANDS
FOR THE GLOBAL ACCELERATOR FOR
PEDIATRIC FORMULATIONS.
IT'S WHO-HOSTED.
PADO-TB IS PEDIATRIC
ANTITUBERCULOUS DRUG
OPTIMIZATION GROUP.
THERE IS A PADO-HIV GROUP THAT
REALLY SETS THE PRIORITIES FOR
DEVELOPMENT IN THE AREA OF
ANTIREANTIRETROVIRAL, AND THEN E
WORKED WITH THE IQ CONSORTIUM
PEDIATRIC WORKING GROUP,
PRESENTER -- DR. JAMES CUMMINS
PRESENTED AT THE EUPFI WHICH IS
THE EU PEDIATRIC FORMULATIONS
INITIATIVE.
WE'LL TALK A LITTLE MORE ABOUT
THE ROME 6 ACTION PLAN.
THEN CONTINUING ON IN THE AREA
OF PREVENTION AND TREATMENT FOR
PREGNANT WOMEN AND CHILDREN, OUR
WORK HAS CONTRIBUTED TO THE
REGULATORY APPROVALS OF TRIUMEQ
FOR CHILDREN DOWN TO
14 KILOGRAMS, DORAVIRINE FOR
ADOLESCENTS ACTUALLY DOWN TO
35 KILOGRAMS, AND THEN CABENUVA
FOR TREATMENT DOWN TO
35 KILOGRAMS.
SO WE'RE VERY THRILLED WITH
THOSE APPROVALS.
WE OF COURSE COLLABORATED WITH
VIIV HEALTHCARE TO COMPLETE THE
SUBMISSIONS FOR TRIUMEC FOR
CHILDREN, AND WE'VE COLLABORATED
WITH GILEAD FOR REMDESIVIR FDA
SUBMISSION IN PREGNANT WOMEN.
WE PARTICIPATED USUALLY YEARLY
ALTHOUGH WITH COVID THERE WERE A
COUPLE YEARS WHERE THIS MEETING
WASN'T HELD WHERE THE WHO, THE
PEPFAR AND THE VATICAN COME
TOGETHER TO CONVENE THIS
MEETING.
THIS ONE WAS THE SIXTH
ITERATION, TO DEVELOP THE ROME V
AND TB TREATMENT AND PREVENTION
IN CHILDREN AND IN PREGNANT
WOMEN.
THERE ARE STAKEHOLDERS PRESENT
FROM ALL SECTORS THAT REALLY
TOUCH HIV AND TB TREATMENT IN
THESE POPULATIONS, AND THEY COME
TOGETHER TO IDENTIFY THE GAPS
AND HAVE EACH OF THE
STAKEHOLDERS MAKE RELEVANT
COMMITMENTS IN THE AREAS THAT
ARE SPECIFIC TO THEM TO MOVE
THINGS FORWARD.
AGAIN, CONTINUING ALONG WITH
PREVENTION AND TREATMENT IN
PREGNANT WOMEN AND CHILDREN,
VERY PLEASED TO SAY THAT THE MTN
ENROLLMENT FOR MTN042 WAS
COMPLETED FOR ALL THREE COHORTS.
THIS IS A STUDY LOOKING AT THE
DAPIVIRINE RING AND ORAL PREP IN
PREGNANT WOMEN.
THEY STARTED WITH THE LATEST
GESTATION, STARTING AT ABOUT 36
WEEKS ENROLLMENT WITH COHORT
ONE, AND THEN SEQUENTIALLY MOVED
FURTHER AND FURTHER BACK TO
EARLIER STAGES ALL THE WAY TO 12
WEEKS WITH COHORT THREE.
SO THE SAFETY INFORMATION FROM
COHORTS ONE AND TWO WILL BE
PRESENTED AT CROI NEXT MONTH AND
FOLLOW-UP OF THE STUDY IS IN
PROGRESS.
SO, NOW KIND OF REFOWS FAUX REFN
WHAT'S COMING NEXT, WHAT DO WE
SEE AS THE CHALLENGES AND
OPPORTUNITIES.
SO SOME OF THIS YOU'VE SEEN
BEFORE.
A LITTLE BIT -- CERTAINLY WE
HAVE MADE PROGRESS AS WE JUST
TALKED ABOUT.
BUT WE'RE STILL FACED WITH A
NUMBER OF CHALLENGES THAT ARE
EVOLVING AS WE GO ALONG.
THE EFFECTIVENESS OF ORAL PREP
AND CABOTEGRAVIR, AS WELL AS
EVENTUAL AVAILABILITY OF THE
DAPIVIRINE INTERVAGINAL RING
WILL DRASTICALLY DECREASE HIV
INFECTION RATES IN STUDIES, AND
WE CERTAINLY HOPE EVENTUALLY IN
THE POPULATION AS A WHOLE, SO
THEN OTHERS HAVE TALKED A BIT
ABOUT THIS, YOU KNOW, WHAT ABOUT
THE RESOURCES TO -- WE KNOW WE
STILL NEED MORE CHOICES, WE NEED
MORE PRODUCTS AND MORE
STRATEGIES TO REALLY OPTIMALLY
REACH ALL THOSE IN NEED OF HIV
PREVENTION, BUT TO CONTINUE IN
THE REALLY TRADITIONAL CLINICAL
TRIALS THAT THE RESOURCES REALLY
BECOME PROHIBITIVE WHEN YOU CAN
GET INCIDENCE RATES AS LOW AS WE
CAN WITH THESE MODALITIES WE
ALREADY HAVE.
SO THERE'S BEEN A LOT OF
DISCUSSION, THE FORUM FOR
COLLABORATIVE RESEARCH HAS
HOSTED AS WELL AS OTHERS, HAVE
HOSTED, YOU KNOW, WORKING GROUPS
AND MEETINGS ON WHAT ARE
ALTERNATIVE POTENTIAL TRIAL
DESIGNS FOR HIV PREVENTION
TRIALS THAT WON'T HOPEFULLY TAKE
AS MANY RESOURCES.
THERE'S BEEN A FAIR AMOUNT OF
DISCUSSION IN A RELATIVELY
RECENT CONSENSUS STATEMENT ON
THE USE OF COUNTERFACTUALS AND
HOW RESEARCHERS CAN GO ABOUT
ESTABLISHING COUNTERFACTUAL HIV
INCIDENCE IN A COMPARATIVE
POPULATION, EITHER
CONTEMPORANEOUSLY OR RECENTLY
CONTEMPORANEOUSLY.
AND WE KNOW THAT SOME OF OUR
PARTNERS AND PARTICULARLY OUR
PHARMA PARTNERS HAVE BEEN USING
THIS COUNTERFACTUAL METHOD, BUT
WE PROBABLY NEED TO, AND THERE
IS CONSIDERATION OF OTHERS,
STILL PROBABLY FURTHER
DISCUSSION, I'VE HAD SEVERAL
PARTNERS COME RECENTLY TO SAY
THAT WE DEFINITELY NEED TO GET
TOGETHER AND DISCUSS, YOU KNOW,
KIND OF THE -- A BIT FURTHER
ABOUT THE WAY FORWARD HERE, SO
THAT IS A GREAT PROBLEM TO HAVE
ON THE ONE HAND, BECAUSE WE HAVE
VERY EFFECTIVE METHODS, BUT A
PROBLEM NONETHELESS THAT WE'LL
NEED TO WRESTLE WITH.
IT WAS BROUGHT UP EARLIER,
COST-EFFECTIVENESS OF NEW HIV
PREVENTION PRODUCTS IS OBVIOUSLY
CRUCIAL.
I KNOW THAT KEN AND HIS GROUP
SHORTLY AFTER THE LAST ARAC, YOU
KNOW, WROTE A PAPER ABOUT THE
ISSUES WITH COST-EFFECTIVENESS
AND THE COST IS QUITE HIGH, WITH
CABOTEGRAVIR LA.
I THINK THAT'S SOMETHING WE'RE
ALL VERY MUCH AWARE OF, AND AS I
THINK YOU ALL KNOW, VIIV HAD
SIGNED AGREEMENTS WITH THE
MEDICINE'S PATENT POOL TO REALLY
TRY VERY HARD TO TRY TO BRING
THOSE COSTS DOWN.
THE CO-CHAIRS OF HPTN804 ALONG
WITH OTHER COLLEAGUES IN SOUTH
AFRICA VERY RECENTLY WROTE
SPECIFICALLY ABOUT THE SCENARIO
FOR SOUTH AFRICA AND GIVEN
POTENTIALLY NEW PREFERENCE FOR
CAB-LA AND, THEREFORE, MORE
DEMAND, YOU KNOW, THEY REALLY
WENT INTO WHAT THE PRICES WOULD
NEED TO COME DOWN TO.
THE QUESTION WAS ASKED ABOUT, DO
WE CONSIDER THESE THINGS,
CERTAINLY WE DO AS WE'RE
THINKING ABOUT NEW PREVENTION
MODALITIES COMING ALONG.
RECOGNIZING THAT ONCE THEY'RE
PROVEN EFFECTIVE AND DEMAND IS
CREATED, THAT THERE'S A LOT OF
PRESSURE TO DECREASE COSTS EVEN
IF IT WAS HIGHER TO BEGIN WITH,
AND SOMETHING THAT WE'RE VERY
MUCH -- THAT WE VERY MUCH
DISCUSS WITH THE PHARMA
COMPANIES AND OTHER PARTNERS AS
WE'RE CONSIDERING TO START THESE
STUDIES THAT THAT IS GOING TO
NEED TO HAPPEN, YOU KNOW, AS
DIANA POINTED OUT, IT'S NOT
SOMETHING THAT WE CAN MANDATE AT
THIS POINT, BUT IT'S CLEARLY
VERY IMPORTANT AND ON EVERYONE'S
MIND.
WE ALSO NEED PRODUCTS, AND I
THINK DIANA DID A REALLY NICE
JOB OF TALKING ABOUT LENACAPAVIR
AND THE POSSIBILITIES THERE.
WE ARE WORKING, WE ARE STARTING
TO WORK WITHIN THE HPTN WITH
GILEAD ON A COUPLE OF -- GILEAD
IS DOING THE TWO LARGE EFFICACY
STUDIES, ONE IN MEN, ONE IN
WOMEN, FOR LENACAPAVIR FOR
PREVENTION, BUT WE'RE LOOKING ON
SOME FOCUSED POPULATION STUDIES
THAT ARE GOING TO BE REALLY
IMPORTANT MOVING FORWARD.
SO LONGER ACTING DURATION IS
SOMETHING THAT WE CONTINUE TO
WORK ON.
AND THEN THE REGULATORY
CHALLENGES, YOU KNOW, WE HAVE
MULTIPURPOSE PREVENTION
TECHNOLOGIES AS ONE OF OUR AREAS
OF FOCUS.
THOSE ARE A GREAT THING, AND
HOPEFULLY THAT WILL PROVE TO BE
SO, BUT THERE ARE SOME
CHALLENGES, AND WORKING WITH
REGULATORS IS GOING TO BE VERY
CRITICAL.
THE FDA RECENTLY PUT OUT SOME
GUIDANCE IN THE LAST YEAR ON
MPTs AND STATING THAT OFTEN
YOU HAVE TWO OR MORE APIs AND
WHERE DO YOU GO, AND THEY MAY BE
WITHIN DIFFERENT GROUPS AT FDA,
AND THEY SAID OKAY, YOU REALLY
NEED TO CONSULT EARLY WITH THE
PRODUCT THAT IS CONSIDERED THE
PRIMARY MODE OF ACTION FOR
WHATEVER IT IS YOU'RE
CONSIDERING STUDYING, AND I
THINK IN OUR ROLE, YOU KNOW, AS
NIH AND A SISTER AGENCY OF FDA,
THAT THAT WILL BE REALLY
IMPORTANT AS WE MOVE FORWARD FOR
US TO MAKE THOSE CONTACTS EARLY.
SO AGAIN, STILL CONSIDERING THE
CHALLENGES FOR THE FUTURE OF HIV
PREVENTION RESEARCH, WE NEED TO
CONTINUE, WE'VE BEEN WORKING,
MANY OF US ALL TOGETHER, FOR A
LONG TIME TO REALLY UND UNDERSTD
HOW TO INDUCE DESIRE, IF YOU
WILL, FOR HIV PREVENTION AND
THEN FOR SPECIFIC HIV PREVENTION
PRODUCTS, THAT'S STILL A
REQUIREMENT, IT HASN'T CHANGED.
WE'VE MADE SOME PROGRESS BUT
WE'VE GOT TO CONTINUE IN THAT
VEIN.
AND THEN AS I SAID EARLIER ON IN
THINKING ABOUT CHOICE, CHOICE IS
NEEDED FOR KEY POPULATIONS AND
HOW TO BEST ENGAGE THESE
POPULATIONS FOR HIV PREVENTION.
IT'S BEEN CLEAR TO US THAT EARLY
INTEGRATION OF BEHAVIORAL AND
SOCIAL SCIENCE INTO OUR STUDIES
IS VERY IMPORTANT, AND THEN
COMMUNITY ENGAGEMENT AND REALLY
FOLLOWING THE GOOD PARTICIPATORY
PRACTICES, IT IS A MUST.
IN ORDER TO COME TOGETHER AS A
GROUP AND BE ABLE TO HAVE
THESE -- IMPROVE OUR
UNDERSTANDING AND MOVE PRODUCTS
FORWARD.
AND THEN IN REALLY DOING THIS
REQUIRES A LOT OF INNOVATION,
AND IT CERTAINLY -- AND THIS IS
A THEME YOU CAN HEAR, IT
REQUIRES PARTNERSHIP.
WE'VE GOT TO MAINTAIN OUR
CURRENT PARTNERSHIPS OF WHICH WE
HAVE MANY, BUT PROBABLY DEVELOP
NEW ONES AND THIS WAS SOMETHING
THAT WE WERE TALKING IN ANOTHER
MEETING RECENTLY ABOUT, YOU
KNOW, HOW DO WE AT NIAID FILL
SPECIFIC SCIENTIFIC GAPS THAT
ARE WITHIN OUR MISSION HERE IN
THE IMPLEMENTATION SPACE BY
WORKING WITH PARTNERS, AND
SOMETIMES THAT MIGHT BE A
RELATIVELY NARROW SLIVER.
SOMETIMES IT MIGHT BE BROADER.
BUT REALLY FOCUSING ON HOW TO BE
MORE INNOVATIVE IN THIS SPACE IS
GOING TO BE IMPORTANT.
SO OUR OPPORTUNITIES.
WE HAVE THE HPTN, WE HAVE A
NUMBER OF OTHER MODALITIES BUT
JUST TO FOCUS A MOMENT ON THE
CLINICAL TESTING AREA
OPPORTUNITIES, THE HPTN-SPECIFIC
AIMS ARE DEVELOPMENT OF NOVEL
ARV-BASED PREVENTION METHODS AND
DELIVERY SYSTEMS, AND AS I SAID
EARLIER, THE FOCUS IS ON
OPTIMIZING AND LONGER DURATION
ANTIRETROVIRALS FOR PREVENTION.
THEN FOCUSING ON THE
MULTIPURPOSE PREVENTION
TECHNOLOGIES, AND THEN THE
INTEGRATED BIOMEDICAL AND
SOCIOBEHAVIORAL PREVENTION
STUDIES.
THESE STUDIES ARE OFTEN LARGE.
THEY'RE QUITE COMPLEX.
WE HAVE MANY LESSONS LEARNED
ALREADY.
IT'S OKAY, YOU CAN STAY ON THIS
SLIDE.
WE HAVE MANY LESSONS LEARNED
ALREADY, AND WE'RE TRYING TO PUT
THOSE INTO ACTION AS WE THINK
ABOUT INTEGRATED STRATEGIES.
NOW CHANGING GEARS A BIT HERE,
THINKING ABOUT THE CHALLENGES
FOR THE FUTURE OF MATERNAL AND
CHILD RESEARCH IN OUR AREAS,
REALLY AS I'VE SAID IN THE
BEGINNING WHEN WE WERE TALKING
ABOUT THE "NEW YORK TIMES"
ARTICLE, OUR ROLE REALLY IS
OPTIMIZING THE PRODUCTS,
OPTIMIZING MATERNAL AND CHILD
ANTIRETROVIRAL THERAPY AND TB
REGIMENS AS WELL.
YOU HEARD ME TALKING ABOUT SOME
OF THE ACCOMPLISHMENTS STARTING
INTO THIS AREA OF IMPROVING THE
CHILD FRIENDLY FORMULATIONS,
BOTH FOR HIV AND TB.
WE'VE GOT TO CONTINUE TO
STRENGTHEN OUR ENGAGEMENT.
THAT WORK CAN ONLY BE DONE
REALLY WITH GAP F, THE INOWE VAI
TER PHARMA COMPANIES AND
GENERICS AND WE TRIED TO LAY THE
GROUNDWORK FOR THAT BUT THAT
WILL NEED TO CONTINUE.
THEN WE'VE GOT TO CONTINUE
SUPPORTING IMPROVED TB
DIAGNOSTICS IN CHILDREN IN ORDER
TO ENABLE TB TREATMENT.
WE TALKED ABOUT INCLUDING
PREGNANT AND LACTATING WOMEN IN
STUDIES EARLIER IN THE PIPELINE.
THIS IS REALLY PARAMOUNT,
ENDORSED BY OUR PRGLAC GROUP, BY
WHO AND OTHERS.
WE'VE GOT TO DO THESE EARLY --
THESE EARLIER FERTILITY AND
EARLY EMBRYONIC DEVELOPMENT
STUDIES, AND POSTNATAL STUDIES
ALSO, SO REALLY THOSE
DEVELOPMENTMEN TALL STUDIES NEED
TO BE DONE, THE PRE-CLINICAL
STUDIES EARLIER, SO THAT WE CAN
HAVE ENOUGH INFORMATION TO GET
PREGNANT WOMEN AND LACTATING
WOMEN INTO STUDIES INTO THE
CLINICAL TESTING EARLIER.
TO DO THAT, THOUGH, REQUIRES
MUCH EARLIER ENGAGEMENT AND
TRANSPARENCY WITH PHARMA.
THAT IS SOMETHING THAT HAS BEEN
A BIT OF A CHALLENGE, IS
UNDERSTANDING WHAT THEIR PLANS
ARE EARLY, HOW THEY INTEND TO
FOCUS, WHAT FORMULATIONS, WHAT
WORK THEY'VE DONE ALREADY, OR
PLAN TO DO, AND WHERE WE CAN
COME IN WITH OUR RESOURCES AND
PRIORITIZE THOSE RESOURCES AS
EARLY AS POSSIBLE AND BE EE
FISH.
EFFICIENT.
AND THEN INCLUSION OF
ADOLESCENTS.
I SAW SOME DISCUSSION OF THIS IN
THE CHAT.
AND CHILDREN EARLIER IN PRODUCT
DEVELOPMENT, AGAIN, A SIMILAR
THING TO PREGNANT AND LACTATING
WOMEN.
WE REALLY NEED TO BE COGNIZANT
OF NEEDING TO DO THIS.
WE NEED TO BE SENSITIVE TO THEIR
NEEDS, BOTH CHILDREN AND
ADOLESCENTS.
I WOULD SAY IT'S PROBABLY PRETTY
SPECIFIC FOR HOW WE PLAN TRIAL
LOGISTICS, HOW WE OPERATIONALIZE
STUDIES FOR ADOLESCENTS IS
REALLY IMPORTANT, AND YOU KNOW,
SOMETHING THAT DID COME UP AT
THE ROME MEETING AND HAS COME UP
A NUMBER OF TIMES, AND I THINK
THAT WE'RE DOING VERY WELL IS,
AS STUDIES THAT ARE PLANNED FOR
ADULTS COME ALONG FOR OUR
SCIENTIFIC REVIEW, ALWAYS ASKING
THIS FOAS STUDIES APPLY TO
CHILDREN OR ADOLESCENTS, AND IF
SO, ARE THERE REASONS -- YOU
KNOW, THE PRODUCT OR THE
STRATEGY MAY APPLY, ARE THERE
REASONS AT THIS STAGE THAT WE
COULDN'T INCLUDE AND NEED TO BE
VERY CLEAR ABOUT THAT, THAT THAT
IS THE CASE, AND IF NOT, THEN WE
REALLY NEED TO CONSIDER
INCLUSION EARLIER.
AND THEN OF COURSE AS WE TALKED
ABOUT, YOU KNOW, ONE OF OUR
MAJOR TASKS ARE TO CONTINUE TO
WORK ON HIV-FREE REMISSION IN
CHILDREN, WHICH WE WILL DO, AND
BACK TO ADOLESCENTS FOR A
MOMENT, I MEAN, I THINK IN SOME
WAYS, WE'VE DONE A PRETTY GOOD
JOB IN THE AREA OF TREATMENT.
WE'VE GOTTEN A NUMBER OF
APPROVALS AS YOU SAW EARLIER,
YOU KNOW, UNDER THE
ACCOMPLISHMENT SECTIONS AND EVEN
PAST APPROVALS FOR
ANTIRETROVIRAL TREATMENT, AND
OPTIMIZING THAT IN ADOLESCENTS.
WE'VE COMPLETED HPTN08301 AND
401 WHICH WERE THE ADOLESCENT
FOCUSED CABOTEGRAVIR STUDIES FOR
PREVENTION AND THE ATN HAS DONE
A LOT OF WORK IN THE AREA OF
ADOLESCENCE DOMESTICALLY
FOCUSED.
FOR US IN THAT SPACE, WE REALLY
NEED TO CONTINUE TO THINK ABOUT
NIAID AND OUR PARTNERS MISSION
OF OPTIMIZING THE PRODUCTS AND
STRATEGIES, AND THEN WORKING
WITH PARTNERS ON THE
IMPLEMENTATION ISSUE SURROUNDING
ADOLESCENTS.
SO WHAT ARE OUR OPPORTUNITIES?
WE HAVE THE IMPACT NETWORK IN
THE CLINICAL AREA, AND THEIR
SPECIFIC AIMS ARE NOVEL AND
DURABLE TREATMENT INTERVENTIONS
FOR HIV, AND THEN ALSO FOR TB
PREVENTION AND TREATMENT.
THEN OTHER COMPLICATIONS AND
COINFECTIONS, AS WELL AS
ART-FREE REMISSION.
WE ALSO HAVE THE RAPPS CONTRACT
HERE.
THIS IS -- I'VE TALKED ABOUT IT
SEVERAL TIMES, BUT YOU SEE DOWN
IN THE BLUE KIND OF SQUARES,
RECTANGLES BELOW, THAT THERE ARE
FIVE MAJOR AREAS THAT THE RAPPS
CONTRACT TASK AREAS THAT WILL BE
ABLE TO BE UNDERTAKEN, AND THEN
YOU CAN SEE, AND I THINK WE NEED
TO HIT THE -- MAYBE THERE'S
ANIMATION HERE.
YES.
AND IF YOU CAN JUST KEEP
CLICKING, THERE SHOULD BE ONE
MORE AFTER THIS.
SORRY ABOUT THAT.
I DIDN'T REALIZE THAT HAD BEEN
TAKEN OUT.
AND YOU CAN SEE HERE UNDER THESE
TASK AREAS, THAT -- OKAY, THAT
WHERE WE COULD BE ABLE TO
CONTRIBUTE PARTICULARLY TO THE
PEDIATRIC FORMULATION WORK,
WHERE WE HAVE THESE
OPPORTUNITIES.
I WON'T GO OVER ALL THE
SPECIFICS OF THOSE.
NEXT, PLEASE.
SO WE'RE BACK TO HOW IT ALL FITS
TOGETHER.
AGAIN, I'VE EXPLAINED THIS BUT
JUST TO BRING YOU BACK TO IT ONE
MORE TIME.
AGAIN, A REMINDER OF OUR
PRIORITY, BRING US ALL BACK TO
WHERE WE STARTED, AND AGAIN, I
THANK EVERYBODY IN PREVENTION
SCIENCES PROGRAM ACROSS THE
DIVISION.
CARL AND SARAH FOR THEIR
LEADERSHIP, THIS COMMITTEE, AND
THANK YOU VERY MUCH.
>>THANK YOU, DR. ZWERSKI.
WHAT AN AMBITIOUS AND IMPRESSIVE
AGENDA, AND REALLY EXCITING
DEVELOPMENTS OVER THE PAST YEAR
AND TWO AND THREE, WITH MORE TO
COME.
THANK YOU.
MAYBE WE'LL TAKE ONE QUESTION,
IF SOMEONE HAS A QUESTION.
DR. GANDHI?
>>YOU KNOW, THAT WAS A GREAT
TALK AND YOU EXPRESSED SOMETHING
THAT I THINK IS REALLY
IMPORTANT, WHICH IS -- IS IT THE
ROLE OF RESEARCH, IS IT THE ROLE
OF NIAID TO HELP ADDRESS
DISPARITIES, LIKE IT IS THE CDC,
LIKE IT IS ALL OF US AS
CLINICIANS OR TREATERS IN THIS
ROOM.
I WOULD ARGUE ALONG WITH YOU
THAT IT IS OUR GOAL, IT IS ROLE
IN OUR RESEARCH STUDIES IN TERMS
OF PARTICIPATORY INCLUSION AND
IN TERMS OF IMPLEMENTATION AND
ROLLOUT.
SO WE'RE AT A POINT WHERE I
THINK IT HAS TO BE EXPLICITLY
STATED IN NIAID PRIORITIES.
THANK YOU.
>>THANK YOU.
TOTALLY AGREE.
>>YES.
LAST QUESTION, DR. ABRAMS.
>>HI, SHERYL.
THANKS.
THAT WAS REALLY FANTASTIC.
AND I THINK WE'VE BEEN REALLY
HAPPY TO SEE NIAID EMBRACE THE
PREGNANCY AND ADOLESCENT AGENDA.
I DO THINK THAT THE PEDIATRIC
COMMUNITY HAS PUT FORWARD
PARTICULARLY FOR ADOLESCENTS NOT
THAT WE HAVE SEPARATE STUDIES
BUT THAT THEY BE INCLUDED IN THE
ADULT STUDIES USING WEIGHT
RATHER THAN AGE AS A CUTOFF,
PARTICULARLY AROUND NEW AGENTS.
AND I DON'T THINK WE'VE GOTTEN
TO THAT POINT YET.
BUT IT WOULD BE FABULOUS AS
WE'RE ASKING THE QUESTION IN THE
ADULT TRIALS, THE HPTN TRIALS TO
SAY IS THERE A REASON THAT YOU
WOULDN'T INCLUDE -- WOULDN'T USE
WEIGHT RATHER THAN AGE.
SO I JUST WANTED TO BRING THAT
UP.
>>THANK YOU.
>>THAT'S A GREAT POINT.
THANK YOU.
OKAY.
WE WILL KEEP MOVING.
THANK YOU, DR. SWER SKI.
SWE ZWERSKI.I'M GOING TO TURN F
CLINICAL SITE OVERSIGHT.
>>THANK YOU, GOOD AFTERNOON,
COUNCIL MEMBERS AND COLLEAGUES.
I HAVE A SLIGHTLY DIFFERENT
CHARGE FROM MY PROGRAM
COLLEAGUES AND INSTEAD OF A
PROGRAM OVERVIEW, I'M GOING TO
KNOW CFOCUS MY PRESENTATION ON S
LEARNED FROM THE COVID PANDEMIC
THAT MAY BE APPLIED TO HIV
RESEARCH.
I ONLY HAVE FOUR SLIDES SO I
THINK I'LL BE ABLE TO MAKE UP A
LITTLE BIT OF TIME.
IMPLEMENTING AND EXECUTING
CLINICAL TRIALS DURING THE
HEIGHT OF THE PANDEMIC.
I'LL BUILD OFF OF WHAT WE'VE
LEARNED RUNNING A PANDEMIC
TREATMENT TRIAL, AS WELL AS
CONTINUING OUR HIV/AIDS NETWORK
TRIALS.
AND DISCUSS OPPORTUNITIES TO
STRENGTHEN OUR HIV/AIDS RESEARCH
ENTERPRISE, AS WELL AS PREPARE
FOR UPCOMING PANDEMIC TRIALS.
SO I'LL SPEAK FIRST TO THE
OPERATIONAL COMPONENTS WHICH
WORKED WELL.
THEN I'LL TALK ABOUT LESSONS
LEARNED AND I'LL WRAP UP
SPEAKING TO OPPORTUNITIES THAT
COULD BE CONSIDERED FOR FUTURE
TRIALS.
SO WE ALL KNOW THAT OUR CLINICAL
RESEARCH SITES EXPERIENCE
SIGNIFICANT OPERATIONAL
DISRUPTION DURING THIS TIME.
THERE WAS TREMENDOUS FEAR AND
UNCERTAINTY AT THE SITES.
THEY WERE DEALING WITH LOSS OF
STAFF, SUPPLY CHAIN DISRUPTION,
CHANGING OPERATING PROCEDURES,
ALL WHILE SITES WERE ALSO
RESPONDING TO THEIR LOCAL
PANDEMIC.
AND THERE WERE THINGS THAT
WORKED WELL DURING THIS TIME.
FIRST, WE WERE ABLE TO REACH OUT
TO OUR GLOBAL NETWORK OF
INVESTIGATORS, AND QUICKLY
ENGAGE THEM TO FACILITATE
DEVELOPMENT AND EXECUTION OF
PROTOCOLS TO MEET THIS EMERGENT
NEED.
INVESTIGATORS WERE ABLE TO DRAW
ON THE INFRASTRUCTURE THAT WE'VE
JOINTLY BUILT OVER MANY YEARS.
MANY OF THESE SITES HAVE
PARTICIPATED IN OUR NETWORK
ENTERPRISE FOR SEVERAL YEARS AND
WE'VE MADE JOINT INVESTMENTS IN
DEVELOPING THE INFRASTRUCTURE,
INCLUDING THE ENGAGEMENT OF
COMMUNITY ADVISORY BOARDS WITHIN
EACH OF OUR CLINICAL RESEARCH
SITES.
WE WERE ABLE TO QUICKLY PIVOT TO
TAKE ADVANTAGE OF THAT
INFRASTRUCTURE TO SUPPORT OUR
COVID PRIORITIES.
WHERE NECESSARY, SOME OF THE
SITES WERE ABLE TO EXPAND OR
SHIFT THEIR CURRENT CLINIC
FOOTPRINT TO ACCOMMODATE BOTH
COVID AND HIV PATIENTS.
WE HAD FRAMEWORKS IN PLACE FOR
SITE EXPANSION AND WE WERE ABLE
TO APPLY THOSE PROCESSES QUICKLY
TO FACILITATE CLINIC EXPANSION.
WE WERE ABLE TO SUPPORT THE USE
OF MOBILE CLINICS THAT CAME
FULLY STAFFED WITH RESEARCH
EXPERIENCE PERSONNEL AT SEVERAL
SITES TO FACILITATE SEPARATION
OF COVID PARTICIPANTS FROM OTHER
RESEARCH PARTICIPANTS.
AND WHERE POSSIBLE AND
PRACTICAL, WE WERE ABLE TO USE
REGIONAL APPROACHES TO
OPERATIONALIZE STUDIES.
FOR EXAMPLE, WE USED REGIONAL
DEPOTS TO SECURE
NON-INVESTIGATIONAL PRODUCT
SUPPLIES IN DIFFERENT PARTS OF
THE WORLD, INCLUDING THE U.S.
TO SHIP STUDY SUPPLIES TO SITES.
AND THIS WAS ESPECIALLY
IMPORTANT BECAUSE OF THE
CONSTRAINTS IN THE SUPPLY CHAIN.
WE WERE ABLE TO LEVERAGE
PURCHASING OF SUPPLIES THAT
INVESTIGATORS MAY OTHERWISE HAVE
NOT HAD ACCESS TO.
AND WE HAVE MANY LESSONS
LEARNED.
FIRST, THE NIAID LONG TERM
INVESTMENT IN OUR SITES ALLOWED
US TO QUICKLY PIVOT THE SITES.
TO CONTRIBUTE TO NIAID'S
EMERGENT PRIORITIES.
OUR NETWORK SITES WERE ABLE TO
MOVE QUICKLY TO PARTICIPATE IN
NIAID SPONSORED COVID RESEARCH
AND DO SO WITH A HIGH LEVEL OF
QUALITY.
THE ROBUST PROCESSES AND
INFRASTRUCTURE AT THESE NIAID
SITES HAVE BEEN REFINED OVER
YEARS, AND RESULT IN HIGH
QUALITY OUTPUTS AND REGULATORY
COMPLIANCE.
AND PROTOCOLS THAT WERE MORE
COMPLEX FACED MORE CHALLENGES
WITH COMPLIANCE.
SIMPLICITY OF PROTOCOL WAS KEY,
ESPECIALLY WORKING ACROSS MANY
SITES.
MANY OF WHICH WE HAD NEVER
WORKED WITH BEFORE.
WE LEARNED THAT SIMPLIFYING THE
PROTOCOL TRANSLATED TO BETTER
COMPLIANCE.
THE MORE COMPLEX AND DEMANDING
THE PROTOCOL, THE HIGHER THE
TENDENCY FOR QUALITY ISSUES AND
SITE DROPOUT.
WE FOUND OUT THAT WHEN WE WERE
CREATING NEW PROCESSES OR HAD TO
CREATE NEW LINKAGES, THAT THEY
TENDED TO PRESENT NEW CHALLENGES
FOR SITES.
THESE TOOK TIME AND EFFORT
DURING A HIGHLY CONSTRAINED TIME
TO DEVELOP, BUT WE ALSO
RECOGNIZE THAT THERE MAY BE A
NEED TO DEVELOP NEW SYSTEMS.
BUT IF POSSIBLE, USE EXISTING
WORKFLOWS BECAUSE OF THE
COMPLEXITY AND EFFORT IN
CREATING NEW SYSTEMS, AND THE
CHALLENGES WITH SITE COMPLIANCE
IMPLEMENTING NEW PROCESSES
DURING THESE VERY CONSTRAINED
TIMES.
WE WERE ALSO CHALLENGED TO
OPERATIONALIZE OUR PROTOCOLS IN
A MANNER THAT MINIMIZED
IN-PERSON INTERACTIONS.
REMOTE APPROACHES REQUIRE AN
INVESTMENT IN TECHNOLOGY AND
TRAINING, AND THESE TOOLS WERE
NOT NECESSARILY IN PLACE AT THE
TIME THE PROTOCOLS WERE ROLLED
OUT, WHICH ALSO CREATED DELAYS
AND SITE CHALLENGES WITH
IMPLEMENTATION.
LASTLY WE LEARNED THE IMPORTANCE
OF HAVING CLEAR, WELL THOUGHT
THROUGH IMPLEMENTATION PLANS.
SITES WERE UNDER EXTRAORDINARY
PRESSURE IN ANTICIPATING AND
UNDERSTANDING THEIR NEEDS AND
ADDRESSING THEM PROACTIVELY WITH
CLEAR DOCUMENTATION AND GUIDANCE
WAS CRITICAL KEEPING SITES MOTOR
THE SERRATMOTIVATED AND FOSTERIG
COMPLIANCE.
SO I'LL WRAW I'LL WRAP UP TOUCHN
OPPORTUNITIES.
FIRST WE SEE AN OPPORTUNITY TO
STRENGTHEN TECHNOLOGY PLATFORMS
AT BOTH THE SPONSOR AND SITES,
TO FACILITATE REMOTE APPROACHES
TO CLINICAL TRIAL
IMPLEMENTATION.
PUTTING TOOLS IN PLACE AND
HAVING STAFF TRAINED AND
PROFICIENT WITH SYSTEMS AND
PROCESSES FOR REMOTE ACTIVITY
SUCH AS E-CONSENT, REMOTE
MONITORING, REMOTE LAB
COLLECTION WOULD FACILITATE
FUTURE RESEARCH.
AND WE TYPICALLY WORK WITH
ACADEMIC RESEARCH INSTITUTIONS
TO CONDUCT HIV/AIDS RESEARCH.
TO HELP REACH POPULATIONS THAT
SOME OF OUR EXISTING SITES DO
NOT EASILY ACCESS.
AND OUR RESEARCH IS GLOBAL.
EX--U.S. REGULATORY APPROVALS
CAN BE QUITE LENGTHY, IN MANY
COUNTRIES EXCEEDING SIX MONTHS.
SO PARTNERING WITH EX--U.S.
REGULATORS TO BUILD
RELATIONSHIPS AND IDENTIFY
OPPORTUNITIES TO EXPEDITE
APPROVALS WOULD ALLOW THE SITES
TO GET STARTED MUCH QUICKER IN
THESE SETTINGS.
LASTLY, HAVING CONTINGENCY PLANS
IN PLACE WITH MECHANISMS THAT WE
CAN QUICKLY ACTIVATE TO MOBILIZE
TRAINED STAFF WITH EXPERIENCED
LEADERSHIP AND CLEAR PROJECT
PLANNING WOULD ALLOW US TO
IMPLEMENT ROBUST PROJECT PLANS
RAPIDLY.
WITH A HIGH LEVEL OF QUALITY.
SO I'LL STOP THERE.
THAT'S THE END OF MY
PRESENTATION.
I DON'T KNOW IF WE'RE HOLDING
QUESTIONS FOR AFTER
DR. WORRELL'S PRESENTATION, BUT
I'M HAPPY TO ANSWER ANY
QUESTIONS ABOUT THE INFORMATION
I SHARED.
>>GREAT.
THANK YOU.
THANK YOU, REALLY HIGHLIGHTING
SOME OF THE CHALLENGES AND
SUCCESSES.
ARE WHY DON'WHY DON'T WE TAKE ON
FROM DR. WALLACE.
IS IT FAWN, DSTEPHAUN, DO YOU HN
>>CAN YOU HEAR ME NOW?
>>YEAH.
>>OKAY.
THANK YOU FOR THAT.
THANK YOU FOR THE PRESENTATION,
MANIZHE.
AMAZINAMAZING WORK IS BEING DONE
ACROSS THE BOARD, AND I WANT TO
ACKNOWLEDGE IN PARTICULAR THE
WORK THAT WAS DONE TO -- WHICH
IS OFTEN NOT HIGHLIGHTED, THE
WORK THAT WAS DONE TO BRING ON
THE HISTORICALLY BLACK MEDICAL
COLLEGES DURING THE COVID WORK,
AND HOW BRINGING ON THOSE
INSTITUTIONS AS
PROTOCOL-SPECIFIC SITES REALLY
SUPPORTED THE COVID-19 RESEARCH
RESPONSE, INCLUDING ACTIVELY
ENGAGING WITH THE COVID-19
PROVISION THAT WERE TRIALS.
THE IMPACT OF BRINGING THESE
SITES ON, I THINK REALLY HELPED
TO ENGENDER TRUST IN KEY
COMMUNITIES, ASSIST IT WITH
BUILDING AND EXPANDING TRUSTED
VOICES IN COVID-19 SCIENCE, AND
OF COURSE SUPPORTED US SEEING
THE DIVERSITY IN THE COVID-19
VACCINE TRIALS THAT WE SAW.
SOME OF THE FEEDBACK THAT I
CONTINUE TO HEAR FROM COLLEAGUES
AND COMMUNITIES IS REGARDING
WHAT IS HAPPENING TO LEVERAGE
THESE SAME INSTITUTIONS, AND NOW
THERE ARE SIX WITH THE INCLUSION
OF MORGAN STATE AND BALTIMORE
AND XAVIER UNIVERSITY IN NEW
ORLEANS, SO NOW THERE ARE A
TOTAL OF SIX, IN HIV RESEARCH
AND TO ENSURE MORE IS BEING DONE
TO DEVELOP KEY PARTNERSHIPS WITH
THESE INSTITUTIONS AND OTHER
MINORITY SERVING INSTITUTIONS.
>>THANK YOU, STEPHAUN, FOR
THAT.
I THINK YOU POINT OUT A REALLY
IMPORTANT ASPECT OF OUR ABILITY
TO ADVANCE THE PANDEMIC RESEARCH
BUT ALSO LINKING IT BACK TO THE
HIV/AIDS RESEARCH.
THE NIAID SORT OF HAD AN
INTEGRATED APPROACH TO BRINGING
ON HBCUs TO SUPPORT NIAID
RESEARCH PRIORITIES.
OUR DMID, OUR SISTER DIVISION,
HAS WORKED CLOSELY, BRINGING ON
SOME HBCUs TO SUPPORT SOME OF
THE PRIORITIES THEY'RE WORKING
IN AROUND COVID -- THE COVID
RESPONSE.
WE HAVE WORKED WITH SOME OF THE
HBCUs WITHIN THE COVPN AND
IT'S A SORT OF INTEGRATED
APPROACH THAT WE'RE PURSUING TO
BE ABLE TO GET MORE EXPERIENCE
WITH THE HBCUs.
WITHIN THE DIVISION OF AIDS, WE
DO HAVE A MODEL THAT RELIES ON
SORT OF A SOLICITATION AND A
GRANT-BASED APPROACH TO
SUPPORTING SITES, AND WE WOULD
WELCOME THEM TO COMPETE IN THE
UPCOMING SOLICITATION THAT'S
GOING TO BE COMING UP.
BUT THERE IS MORE OF AN
INTEGRATED APPROACH ACROSS THE
INSTITUTE INVOLVING THE HBCUs
IN THE RESEARCH PRIORITIES.
>>GREAT.
THANK YOU, MANIZHE.
WE'RE GOING TO MOVE TO OUR LAST
PRESENTATION.
THE OFFICE FOR POLICY AND
CLINICAL RESEARCH OPERATIONS,
DR. CAROL WORRELL, AND THEN
WE'LL HAVE SOME TIME FOR -- A
FEW MINUTES FOR DISCUSSION AT
THE END.
>>THANK YOU, KEN, AND THANK YOU
FOR THE OPPORTUNITY TO PRESENT.
OKAY.
SO I'M GOING TO PRESENT LESSONS
LEARNED FROM THE PANDEMIC, FROM
A CLINICAL TRIAL OPERATIONS
PERSPECTIVE.
I WANTED TO MAKE SURE I
ACKNOWLEDGE MY TEAM, SO I PUT
THIS SLIDE FIRST.
THIS GROUP HAS RESPONDED
TREMENDOUSLY THROUGHOUT THE
PANDEMIC, AND I WANTED TO ALSO
ACKNOWLEDGE SOME OF OUR FORMER
STAFF MEMBERS WHO ALSO MADE
REALLY SIGNIFICANT CONTRIBUTIONS
BEFORE THEY LEFT.
SO WHAT WORKED?
THE SCIENCE WAS READY.
THE ALL OF GOVERNMENT APPROACH
WHICH BROUGHT RESOURCES NEEDED
TO MEET THE CHALLENGE, AND I
WON'T GO INTO THAT IN DEPTH
BECAUSE I BELIEVE MARY ALREADY
DID.
AND THIS INCLUDES THE ALL OF
NIAID RESPONSE, WHERE NIAID
LEVERAGED ALL OF ITS NETWORKS.
ALL OF THE NETWORK
INFRASTRUCTURE.
THE SUCCESS OF A FULL TIME
REMOTE WORKING ENVIRONMENT WAS A
LITTLE BIT UNEXPECTED AND
SOMEWHAT OF A SURPRISE, BUT IT
WORKED EXTREMELY WELL.
THE USE OF REMOTE TECHNOLOGY
SUCH AS E CONSENT AND REMOTE
MONITORING, ALTHOUGH THEY WERE
LIMITED, WAS EXTREMELY HELPFUL.
WE ACTUALLY WERE LUCKY IN
RECEIVING ADVICE AND WORKING
WITH FORMER INDUSTRY EXECUTIVES
WITH DECADES OF EXPERIENCE
REGARDING SOME OF OUR
OPERATIONAL CHALLENGES.
AND THE ABILITY AND WILLINGNESS
OF DAIDS STAFF TO ABSORB AND ACT
ON THE STEEP AND RAPID LEARNING
CURVE WITH RESPECT TO
OPERATIONAL MODELS WAS REALLY
IMPRESSIVE.
SO I WANT TO DRAW YOUR ATTENTION
TO THESE LAST THREE BULLETS,
WHICH SHOW THE PROGRESSION --
SHOW HOW WE PROGRESSED
OPERATIONALLY, SO STARTING WITH
ACTIV 2, WE STARTED WITH A FULL
SERVICE CLINICAL RESEARCH
ORGANIZATION MODEL, MEANING WE
CONTRACTED OUT ALL OF OUR
OPERATIONS TO A SINGLE CRO.
FOR ACTIV 2B AND 2C, WE WERE NOT
HAPPY WITH THAT.
ACTIV 2B AND 2C WHICH ACTUALLY
NEVER GOT OFF THE GROUND, WE
WERE GOING TO FOLLOW A
FUNCTIONAL AREA MODEL WHERE WE
CONTRACTED OUT PARTS OF OUR
OPERATIONS, AND FOR A5418, WHICH
IS THE MPOX TRIAL, WE ENDED BACK
WHERE WE STARTED WITH A NORMAL
NETWORK TRIAL THAT WAS MADE
POSSIBLE DUE TO SOME
IMPROVEMENTS IN OUR
INFRASTRUCTURE.
SO IN TERMS OF WHAT DIDN'T WORK,
WE RUSHED.
AS YOU RECALL, WE STARTED IN
MARCH OF 2020, AND EVERYONE IN
THE SCIENTIFIC COMMUNITY FELT WE
WERE ALREADY WAY BEHIND.
SO ACTIVE 2 WAS DAIDS AND THE
ACTG'S FIRST ATTEMPT TO
IMPLEMENT AN ADAPTIVE PLATFORM
TRIAL.
IT TH TRIAL WAS LARGE, HAD AN
ELEGANT DESIGN, VERY M A BISHES
GOALS AND OUR EXISTING TRIAL
INFRASTRUCTURE COULD NOT SUPPORT
IT.
IN THE PROCESS OF AUGMENTING OUR
EXISTING CAPABILITIES WOULD HAVE
DELAYED THE TRIAL OPENING BY
SEVERAL WEEKS IF NOT MONTHS, AND
BY CAPABILITIES IN
INFRASTRUCTURE, I MEAN BOTH
WITHIN DAIDS AND OUR NETWORKS.
SO IN TERMS OF THE COMPLEXITY OF
THE TRIAL DESIGN AND THE MOVE
AWAY FROM OUR EXISTING
INFRASTRUCTURE PROVED TO BE A
MISTAKE.
I WAS PART OF MAKING THAT
DECISION WITH MANY UNINTENDED
CONSEQUENCES.
BUT AS IS TRUE IN THE
GOVERNMENT, IT TOOK A VILLAGE TO
MAKE THAT JUDGMENT AND THERE WAS
QUITE A BIT THAT WE COULDN'T
REALLY FORESEE.
SO I WOULD JUST SAY BUILDING NEW
TRIAL INFRASTRUCTURE AND NEW
TRIAL DESIGNS IN THIS CONTEXT,
YOU SHOULD JUST NOT DO THAT.
DAIDS ALSO SOMETHING THAT REALLY
GOT IN OUR WAY WAS OUR ACCESS TO
FEDERAL CONTRACT MECHANISMS, SO
WHEN WE HAD TO USE -- THERE WAS
ONLY ONE VEHICLE WE COULD USE,
IT WAS NOT DESIGNED TO
ACCOMMODATE CLINICAL TRIALS.
AND IT FORCED THE USE OF A
SINGLE CRO.
WE DIDN'T HAVE ANY COMPETITION
THERE.
SO THE COMPLEXITY OF THE TRIAL
DESIGN AS I'VE SAID SEVERAL
TIMES IN THIS SLIDE INTRODUCED
EXCEPTIONAL AMOUNTS OF OPERATION
COMPLEXITY.
THE STAFF HAD TO CREATE NEW
PROCESSES FOR DAIDS OVERSIGHT,
WHICH WAS AN ENORMOUS AND
TIME-CONSUMING JOB.
AND ALSO AS A RESULT OF SOME OF
THOSE CHANGES, WE HAD TO DEAL
WITH RECONFIGURING OUR CLINICAL
RESEARCH MANAGEMENT SYSTEM,
CRMS, WHICH INVOLVED UNRAVELING
HOW THE PROCESSES MOVE THROUGH
THE SYSTEM AND WERE
INTERCONNECTED, AND THAT WAS
EXTREMELY LABOR-INTENSIVE AND
TIME-CONSUMING, AND LED BY OUR
PROTOCOL REGISTRATION STAFF AND
THE MAIN EFFORT WAS LED BY
MANIZHE.
AS THE PANDEMIC WORE ON, STAFF
ATTRITION INCREASED, PARTLY DUE
TO COMPETITION FROM INDUSTRY AND
RETIREMENTS, BUT ALSO FOR
VARIOUS REASONS INCLUDING JUST
INABILITY TO CONTINUE TO
TOLERATE THE WORK.
SO WHAT ARE OUR OPPORTUNITIES
AND PATHWAYS FORWARD?
OBVIOUSLY WHEN WE DO THIS AGAIN,
WE'LL KEEP THINGS SIMPLE, BUT I
WOULD SAY SIMPLE IN THIS CONTEXT
IS ALREADY RIDICULOUSLY
COMPLICATED.
STICK TO WHAT WE KNOW,
ESPECIALLY WHEN WE'RE HURRIED.
DAIDS AND ITS NETWORK
COLLABORATORS WILL CONTINUE
THEIR EFFORTS TO IMPROVE OUR
EXISTING INFRASTRUCTURE IN THE
CONTEXT OF PLANNING FOR SUCCESS
AND ENDING THE HIV PANDEMIC,
WHICH WILL HOPEFULLY LEAVE US
BETTER PREPARED FOR A FUTURE
PANDEMIC, WHICH I THINK WE ALL
AGREE IS LIKELY.
AND JUST TO REFER BACK TO THE
LAST SLIDE, IT WAS IMPROVEMENTS
IN INFRASTRUCTURE THAT ALLOWED
US TO RETURN BACK TO OUR REGULAR
NETWORK STRUCTURE.
AND EVEN IN TRIAL DESIGN, I
WOULD SAY IT WAS AN IMPROVEMENT
FOR MPOX THAT PREGNANT WOMEN AND
CHILDREN COULD BE INCLUDED.
BUT I'M A PEDIATRICIAN, SO WHAT
CAN YOU SAY?
WE ALREADY HAVE EVIDENCE OF
HOW -- AS I SAID, OF HOW THESE
IMPROVEMENTS CAN HELP, AND A5418
OPENED IN SEVEN WEEKS, WHICH WAS
A RECORD.
DAIDS HAS INITIATED -- MOVING
FORWARD, DAIDS HAS INITIATED A
WORKING GROUP AS WE DO TO
IDENTIFY AND ADDRESS GAPS IN ITS
PROCESSES, INCLUDING THE USE OF
REMOTE TECHNOLOGY FOR CLINICAL
TRIAL PARTICIPATION AND
OPERATIONS.
WE'LL CONTINUE TO DEVELOP AND
REFINE OUR PROCESSES.
AND ON A MORE INTERESTING NOTE,
WE STARTED WORK WITH ELECTRONIC
SYSTEMS CONSULTANTS TO ATTEMPT
TO REDUCE THE COMPLEXITY OF THE
LARGE NUMBER OF SYSTEMS REQUIRED
TO CARRY OUT EACH CLINICAL
TRIAL, WHICH IS USUALLY MORE
THAN 20 DIFFERENT SYSTEMS FOR
TRIAL, BOTH WITHIN DAIDS AT OUR
VENDORS -- AT OUR -- SORRY --
GRANTEES AND AT SITES.
AND TO REDUCE THE BURDEN ON
USERS.
AND OBVIOUSLY GOING BACK TO THE
PAPANDEMIC, WE OBVIOUSLY NEED
SCIENCE THAT IS MATURE ENOUGH TO
MOVE FORWARD TO CLINICAL TRIALS,
WHICH IS AS MUCH OF A STATEMENT
AS I AM ALLOWED TO MAKE AS AN
EMPLOYEE OF THE EXECUTIVE
BRANCH.
SO THAT IS THAT.
I'M DONE.
AND I WILL BE HAPPY TO ANSWER
ANY QUESTIONS ABOUT SOME OF THE
CHALLENGES WE'VE FACED.
>>THANK YOU, DR. WORRELL.
I HAVE ALWAYS THOUGHT THAT I'VE
LEARNED MORE FROM MY OWN
FAILURES THAN SUCCESSES AND I
THINK YOUR CANDOR AND ABILITY TO
DESCRIBE SOME OF THE CHALLENGES
IS BOTH REFRESHING AND HELPFUL
TO ALL OF US.
SO WE HAVE ABOUT -- LET'S SEE IF
WE HAVE A QUESTION FOR
DR. WORRELL, AND THEN WE HAVE
FIVE MINUTES FOR BROADER
DISCUSSION.
SO ANYTHING SPECIFIC?
WHY DON'T WE OPEN IT UP BROADLY
AND LET ME REMIND FOLKS THAT THE
ECB HAS ALL OF THE SLIDES FROM
ALL OF THE PRESENTATIONS,
TREMENDOUS AMOUNT OF REALLY
EXCITING DATA, SO PEOPLE CAN
LOOK AT THOSE GOING FORWARD AS
WELL.
DR. GUPTA.
>>YES, HI.
THANK YOU.
IT BEEN AN INCREDIBLE SORT OF
INFORMATION AND SORT OF
REFLECTION OF SO MUCH LESSONS
LEARNED AND JUST SO MUCH
HAPPENING AT THE LEVEL OF DAIDS.
IT'S THRILLING.
IT'S NEVER A DULL MOMENT.
SO I THINK I BROUGHT THIS UP
SORT OF EARLIER WHEN WE HAD OUR
SMALLER GROUP CALL IN
PREPARATION FOR THIS, BUT I'M
REALLY SORT OF INTERESTED TO
KNOW HOW DAIDS IS TAKING ON THE
SORT OF REVIEW OF WHAT KIND OF
INVESTMENT WILL HAPPEN WITH
TECHNOLOGY TO DO RAPID
DEPLOYMENT OF TRIALS FOR
PANDEMICS, FOR NEW THERAPEUTICS,
TO REALLY LEVER UP THE TIMELINES
AND EFFICIENCIES, IF YOU WILL.
I MYSELF AM GETTING BOMBARDED BY
ALL THESE COMPANIES THAT HAVE
THESE REALLY INCREDIBLE
PLATFORMS FOR DOING TRIALS
ACROSS THE GLOBE, AND HAVE ALL
SORTS OF BELLS AND WHISTLES, AND
SO I'M JUST INTRIGUED BY ALL
THAT YOU'VE LEARNED FROM THIS,
HOW ARE WE GOING TO DO IT BETTER
WITH AT LEAST THAT IN MIND,
SINCE THAT WAS ONE OF THE POINTS
YOU, CARL RAISED AND A FEW
OTHERS HAVE BROUGHT UP.
>>SO I CAN START WITH IT.
SO WITH THE BRINGING ON BOARD
THE CONSULTANT, WHAT WE'RE
TRYING TO DO IS ADDRESS, YOU
KNOW, ADDRESS OUR ELECTRONIC
SYSTEMS AND OUR COMPUTER WORK,
OUR SOFTWARE, ET CETERA, IN A
MORE HOLISTIC AND COMPREHENSIVE
WAY.
WHAT WE'VE DONE IN THE PAST IS
PATCH THINGS, STICK IN NEW
MODULES AS NEEDED.
WE HAVE A LOT OF LEGACY SYSTEMS
AND WE'VE DONE THESE COMPLEX
WORK AROUNDS TO ACCOMMODATE
ADDING NEW THINGS TO THEM.
AND AT THIS POINT, WHAT WE WOULD
LIKE TO KNOW IS HOW TO
STREAMLINE ALL OF THAT, HOW TO
MAKE IT MUCH MORE EFFICIENT, HOW
TO IMPROVE THE USER EXPERIENCE,
AND ALSO HOW TO POSITION
OURSELVES AS WE MOVE FORWARD IN
THE NEXT FIVE TO 10 YEARS.
SO THAT'S WHERE WE'RE WORKING IN
COLLABORATION WITH NIAID'S IT
GROUP, AS WELL AS ODDSET, WHICH
IS A NEW GROUP THAT DEALS WITH
DATA SHARING.
SO WE'RE HOPING WE GET SOMETHING
USEFUL OUT OF THIS.
>>IT'S NO SMALL TASK, SO THANK
YOU FOR AT LEAST SHARING A
LITTLE ABOUT IT.
>>THANK YOU.
MAYBE TWO MORE QUESTIONS AND
THIN I KNOW CARL HAS SAID
THERE'S SOMETHING WE NEED TO DO
BEFORE THE END.
DR. FRANK.
>>THANKS, KEN.
SO TWO-PART QUESTION FOR ANYBODY
WHO'D LIKE TO ANSWER.
I WANT TO GO BACK TO SOME OF THE
SUCCESSES OF THE DELANEY
COLLABORATORY, AND HIGHLIGHT
THAT AS A GREAT EXAMPLE OF
INTERDISCIPLINARY COLLABORATIVE
SCIENCE, AND I'M WONDERING HOW
THE GROUP DECIDES WHEN TO PUT
TOGETHER LIKE BIG COLLABORATIVE
EFFORTS TO TACKLE PROBLEMS
VERSUS FUNDING A HANDFUL OF
R01s.
HOW DO YOU BALANCE THOSE
DECISIONS, AND THEN LIKE ON THE
OTHER SIDE, WE'VE GOT NETWORKS
LIKE THE HVTN AND THE ACTG THAT
HAVE FREEZERS FULL OF SPECIMENS
THAT AREN'T BEING ANALYZED, BUT
THEREIN PROBABLY LIES SOME
INTERESTING DATA AND RESULTS.
SO HOW DO YOU MAYBE BRING SOME
OF THOSE SPECIMENS OUT FROM THE
NETWORKS AND MAKE THEM MORE
ACCESSIBLE TO SCIENTISTS AT
LARGE?
>>I'LL TAKE THAT ONE ON.
>>GOOD.
>>THAT'S A REALLY IMPORTANT
QUESTION.
ONE OF THE FIRST THINGS I DID
WHEN I GOT TO DAIDS 25 YEARS AGO
WAS SEE IF WE COULD WORK OUT AN
AGREEMENT FOR SPECIMEN SHARING
WITH THE NETWORKS AND THERE
WAS -- THOSE ARE OUR SPECIMENS.
YOU CAN'T TOUCH SPECIMENS UNTIL
THE TRIAL IS OVER.
SO THERE'S A BARRIER THAT IS
REAL WITH THAT.
SPECIMENS ARE AVAILABLE, AND I
THINK EVERY FIVE OR 10 YEARS WE
ADVERTISE THAT THESE ARE
AVAILABLE, NOT JUST IN MAX WISE,
ACTG, PNN DOEPTN DOES A REALLY B
MAKING THEIR SPECIMENS AVAILABLE
AND HAVE -- HAD PROCESSES THAT
ARE UP AND GOING.
BUT IN SOME WAYS IT'S PARTLY
INCUMBENT ON THE NETWORKS TO
ALSO ADVERTISE THAT THESE
ACTIVITIES, THESE GEMS ARE
AVAILABLE.
SO I THINK WE ALL HAVE A
RESPONSIBILITY TO DO A BETTER
JOB OF NOT JUST FOCUSING ON THE
NEXT.
WITH REGARD TO THE NOTION OF
WHAT YOU DECIDE TO COMPETE, LIKE
THE COLLABORATORIES VERSUS
R01s, WE'VE HAD R01s IN THE
CURE SPACE FOR A DECADE OR MORE.
THEY WERE -- BECAUSE THE PROBLEM
WAS SO MULTIDISCIPLINARY IN
TERMS OF THE CHALLENGE, WE FELT
IT WAS ESSENTIAL TO TRY A NEW
MODEL.
THAT WOULD THEN BRING IN A WHOLE
RANGE OF DIFFERENT PEOPLE.
IN SOME WAYS THE CHAVIS STARTED
THAT IN THE VACCINE SPACE
THAT -- OVER TO THE
COLLABORATORY AND INTO CURE.
>>I THINK IT'S BEEN REALLY
SUCCESSFUL, THE COLLABORATORIES.
I WOULD URGE YOU TO DO IT MORE
IN AREAS LIKE AGING AND MAYBE
CARDIOVASCULAR DISEASE OR, YOU
KNOW, OTHER IMPORTANT
COMPLICATIONS IN PEOPLE WITH
HIV.
>>I WOULD AGREE WITH THAT.
THE ISSUE IS, THERE'S SOMETHING
CALLED A SWIM LANE, AND AGING IS
NOT MY PRIMARY SWIM LANE, NOR IS
CARDIOVASCULAR DISEASE.
I'M MORE THAN HAPPY TO
COLLABORATE, WE AS A DIVISION,
WITH THE AGING INSTITUTE AND
WITH NHLBI TO TACKLE THESE
QUESTIONS, BUT IT'S GOING TO
REQUIRE PARTNERSHIP.
AND MAUREEN TALKED ABOUT THAT
QUITE A BIT.
>>AGING IS BECOMING MANY OF OUR
SWIM LANE, I'M AFRAID, CARL,
BUT --
>>WE'RE LIVING IT, RIGHT, KEN?
>>WE ARE LIVING IT.
I KNOW THAT NO ONE NEEDS TO
CATCH A FLIGHT, AND I REALLY
DON'T LIKE TO GO OVER, BUT WE'RE
GOING TO GO OVER BY 3 MINUTES.
RICH HAS A QUESTION, THEN CARL
THERE'S ONE MORE THING WE NEED
TO DO.
IF YOU DO HAVE A FLIGHT, I'M NOT
SURE WHY, YOU WEREN'T SUPPOSED
TO BE IN BETHESDA, BUT ANYWAY,
RICH AND THEN CARL AND THEN WE
WILL TIE UP.
>>I'M GOING TO YIELD THE FLOOR.
I'VE CHATTED MY QUESTION TO THE
ONE DAIDS PERSON THAT IS
RELEVANT.
>>OH, THANK YOU.
THANK YOU, RICH.
CARL, THERE WAS SOMETHING ELSE
THAT WE NEED TO DO.
>>RIGHT.
WE HAVE TO DO ONE MORE EN BLOC
ACTION, ACCEPTING ALL OF THE
RECOMMENDATIONS AND THE THINGS
THAT WE VOTED ON TODAY, WHICH
PRETTY MUCH IS JUST THE SBIRs,
SO IF YOU WILL CALL FOR AN EN
BLOC ACTION TO COVER TODAY'S
AGENDA, THAT WOULD BE
SUFFICIENT.
>>YES, IF WE COULD HAVE AN EN
BLOC ACTION TO COVER THE AGENDA,
THAT WOULD BE GREAT.
I THINK IF SOMEONE COULD APPROVE
THAT?
>>SO MOVED.
>>MOVED.
>>GREAT.
OKAY.
ANYONE OPPOSED?
NO.
ALL RIGHT.
SO THOSE ARE APPROVED.
LET ME ALSO THANK PAM FOR
ORGANIZING THIS, AND EVERYONE
WHO PUT TOGETHER GREAT
PRESENTATIONS, SO MUCH GREAT
SCIENCE.
IT IS REALLY ENCOURAGING FOR
EVERYONE SO KUDOS TO ALL OF YOU.
AND APOLOGIES THAT WE'RE A FEW
MINUTES OVER.
>>KEN, I THINK I SPEAK FOR
EVERYBODY THANKING YOU FOR YOUR
GREAT LEADERSHIP ON THIS
COMMITTEE.
>>THANK YOU.
>>WE WILL MISS YOU, KEN.
>>YES.
>>THANK YOU, KEN!
>>IT'S BEEN A PLEASURE TO WORK
WITH YOU.
>>CERTAINLY MY PLEASURE WITH
EVERYONE.
AND WE WILL HAVE MANY
OPPORTUNITIES TO CONTINUE TO
WORK TOGETHER.
SO THANKS.
THANKS TO EVERYONE.