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