WELCOME, EVERYONE, I'M KEN FREEDBERG FROM MASS GENERAL HOSPITAL. I WANT TO WELCOME EVERYONE TO THE FALL MEETING OF AIDS RESEARCH ADVISORY COMMITTEE MEETING AND THANK EVERYONE FOR BEING HERE AND PARTICIPATING. IT CONTINUES TO BE SUCH A CHALLENGING TIME FOR EVERYONE AND EFFORTS TOWARDS ARAC ARE VERY MUCH APPRECIATED. I WOULD LIKE TO HAVE A MOTION TO ACCEPT THE MINUTES FROM THE JUNE MEETING. >> SO MOVED. >> THANK YOU. >> ANYONE SECOND THE MOTION? >> SECOND. ANYONE WANT TO DEBATE THOSE MINUTES? NO DEBATE. SO, WE WILL THEN APPROVE THE MINUTES OF THE JUNE MEETING. THANK YOU. I WANT TO REMIND EVERYONE THAT OUR JANUARY MEETING WILL BE VIRTUAL REGARDLESS OF HOW MUCH IMPROVEMENT IS MADE IN THE PANDEMIC, WHICH WE ARE LOOKING FORWARD TO AND HOW LOVELY THE WEATHER MIGHT BE IN BETHE IS BETH. DON'T SHOW UP IN JANUARY OR YOU WILL BE ON YOUR OWN. OK. I WILL TURN IT OVER TO Dr. DIEFFENBACH FOR HIS DIRECTOR'S REPORT. >> THANK YOU SO MUCH, KEN. IT'S A PLEASURE TO JOIN YOU TODAY AND SHARE MY REPORT. AS I BEGAN, I'D LIKE TO THANK KIMBERLEY SMITH, SENIOR VICE PRESIDENT IN CHARGE OF RESEARCH ON THE HEALTHCARE FOR HER SERVICE AND COMMITMENT TO THE NIAID COMMITMENT AND AIDS RESEARCH. SHE'S A FANTASTIC MEMBER OF THIS COMMITTEE AND SHE'S NOW ROTATING OFF. BECAUSE I CAN'T NOT DO THIS IN-PERSON, THIS IS THE CERTIFICATE THAT WILL BE SEPTEMBER TO KIMBERLEY THAT HAS BEEN SIGNED BY Dr. FAUCI AND BY ME. THANK YOU TO KIM FOR HER SERVICE. AT THE LAST MEETING, WE DISCUSSED THE DAVID BYRNES WAS RETIRING AS CHIEF OF THE CLINICAL PREVENTION RESEARCH BRANCH IN THE PROVINCIAL SCIENCES PROGRAM. IT'S MY PLEASURE TO ANNOUNCE NEXT SLIDE. Dr. ADAA HAS BEEN APPOINTED THE CHIEF OF THE CLINICAL PREVENTION RESEARCH BRANCH AND IS REPLACING DAVID. ADDIE, SHE WAS AT THE DAIDS FOR NINE YEARS AND AS A PHYSICIAN SHE'S HELPED ACCELERATE IMPORTANT ASPECTS OF HIV PRE EXPOSURE PROFILAXIS WORK AND A MAJOR PLAYER IN THE TRIALS. SHE'S BEEN INVOLVED IN TREATMENT AS PREVENTION FOR PEEDS AND WORKED IN NIGERIA, THE UNITED STATES AND CANADA AND A FELLOW OF THE AMERICAN ASSOCIATION OF FAMILY PHYSICIANS IN A CERTIFIED CANADIAN FAMILY PHYSICIAN. IT'S A PLEASURE TO HAVE HER FULFILL THIS LEADERSHIP ROLE AND I'LL JUST SAY ONE OTHER THING, SHE'S BEEN ROTATED OUT A COUPLE OF TIMES. SHE'S IN THE CORE, AS YOU CAN SEE FROM HER UNIFORM. AND SHE IS JUST BEEN A SUPERSTAR FOR US. MOVING TO THE BUDGET, NEXT SLIDE, PLEASE. SO THIS IS THE CURRENT STATE OF WHAT HAS BEEN PROPOSED. YOU CAN SEE THERE IS A RELATIVELY LARGE BUDGET INCREASE FOR THE NIH OVER ALL OF 21%. A LARGE PIECE OF THAT, AS PROPOSED, IS GOING TO ARPAH WHICH SAY NEW PROGRAM WHICH WILL BE HOUSED IN THE OD AND THAT'S STILL BEING WORKED OUT AS TO WHAT MOST LIKELY WILL BE WORKING ON AS IT COMES ON BOARD. AGAIN, BECAUSE WE DON'T HAVE A FINAL BUDGET AEL OCCASION, YOU CAN SEE WHAT IS PROPOSED IN THE PRESIDENT'S BUDGET. NEXT SLIDE, PLEASE. SO, IN THE MEANTIME, THE HOUSE, IN JULY, PASSED FY22 SPENDING PACKAGE. AND IT'S A LITTLE DIFFERENT. IT HAS LESS MONEY FOR RAPAH AND MORE MONEY FOR THE INSTITUTES AND AGAIN WHAT WE HAVE IN USUALLY WAY, IS WE ARE MOVING TOWARDS A DECISION WITHIN THE CONGRESS ABOUT ACTUAL ALLOCATIONS AND IT'S OUR ANTICIPATION THAT WE WILL START THE YEAR UNDER A CONTINUING RESOLUTION AND I JUST THINK THERE'S SO MUCH TO GET IRONED OUT. FOR THAT REASON, WE'RE GOING TO START ON A CONSERVATIVE LEVEL WITH AN ESTABLISHED P.I. PAY LINE OF THE TENTH PERCENTILE AND THE NEW P.I.s WIL WILL HAVE A 14 PERCENTILE AND RO1s AND WE HAVE PLANS TO CUT COMPETING RESEARCH INITIATIVES UP TO 20% AS NEEDED AND WITH A LOCAL TOWARD END WITH 22%. WE START CONSERVATIVELY SO THERE'S NO SURPRISES AND WHEN THE BUDGET IS PASSED, WE COME BACK AND MAKE CHANGES. THIS IS OUR F Q2 2 PLAN AND IT'S SIMILAR TO WHAT WE WERE DOING IN FISCAL YEAR '21. SO THE NEXT SLIDE GETS INTO A LITTLE BIT MORE OF THE DETAILS ABOUT THE MONEY THAT IS COME TO NIH AND NIAID FOR THE COVID-19 RESPONSE. IT'S DIVIDED INTO TWO SEGMENTS. MONEY THAT WAS ALLOCATED DIRECTLY TO NIH TOTALING $4.8 BILLION. IT WAS DIVIDED UP, AS YOU CAN SEE THERE, TO $1.5 BILLION TO NIAID AND $3.3 BILLION TO OTHER INSTITUTES. THE MONEY THAT -- THE 1.5 BILLION WAS USED TO FUND THE BROADER RATE OF INTERMURAL AND EXTRAMURAL RESEARCH FOCUSED ON FUNDAMENTAL KNOWLEDGE OF SARS-CoV-2 LOOKING AT DISEASE PROGRESSION OUTCOMES AND RECOVERY AND ALSO TO ADVANCE THE DEVELOPMENT AND TESTING OF SAFE AND EFFECTIVE VACCINES AND SOME WORK ON THERAPEUTICS AND DIAGNOSTICS. THE $3.3 BILLION THAT WENT TO NIH IN ADDITION TO COMPLIMENTING NIAID'S ACTIVITIES, ALSO INCLUDED $1.9 BILLION TO FOR NEW DEVELOPMENT AND NEW ASSAYS AND THIS IS THE RAD X PROGRAM AND ALSO INCLUDED $1.5 BILLION TO SUPPORT THE LONG-TERM ANALYSIS OF THE LONG-TERM CONSEQUENCES OF SARS-CoV-2 INFECTION ALSO KNOWN AS LONG COVID. THE BOTTOM HALF OF THE TABLE IS MONEY THAT CAME DIRECTLY FROM THE OFFICE OF THE SECRETARY THROUGH OTHER APPROPRIATIONS THAT $1.7 BILLION WENT TO HEAVILY FUND THE EFFICACY TRIALS THAT NIAID HAS PARTICIPATED IN WITH COVPN AND FUNDING FOR ACTIVE AS WELL. ADDITIONALLY, THERE WAS 3.2 BILLION ALLOCATED TO NIH AND NIAID FOR THE PROGRAMS AND I'LL SAY MORE ABOUT THIS IN A LITTLE BIT. THE TOTAL AMOUNT THERE WAS $4.9 BILLION. IN TERMS OF SCIENTIFIC AND PROGRAM UPDATES, I WANT TO TALK ABOUT THE TRIAL LAUNCHED IN 2017 AND IT ENROLLED A LITTLE OVER 2,600 WOMEN AND AFRICA AND EVALUATING THE J AND J VACCINE AS IT HAD 23 VECTOR WITH A GP140CLADEC BOOST. IT WILL NOT MEET THE CRITERIA NEEDED. IT HAD A INSIGNIFICANT PROTECTION FROM INFECTION AND THEREFORE IT DID NOT MEET THE GO CRITERIA AND IS CURRENTLY STOPPED. IT WAS NOT WHAT WE WERE SEEKING BUT IT WILL REDOUBLE OUR EFFORTS TO CONTINUE TO SEEK A SAFE, EFFECTIVE AND DURABLE HIV VACCINE. NEXT SLIDE, PLEASE. IN PARALLEL, THE MOSAIC TRIAL, WHICH IS IN MEN AND TRANSGENDER AND INDIVIDUALS IN THE AMERICAS AND EUROPE, HAS MOVED FORWARD AND IT LAUNCHED IN SEPTEMBER OF 2019. FULLY ENROLLED IN SEPTEMBER OF '21 AND USE AS I VERY SIMILAR VACCINE IN THAT IT USES THE SAME MOSAIC COMPONENT AND HAS A DIFFERENT PROTEIN BOOST. IT IS OUR INTENTION TO CONTINUE THIS STUDY. IT JUST COMPLETED ENROLLMENT AT THE TIME. AGAIN, WE WILL COME BACK AND REVISIT THIS AS MORE DATA BECOMES AVAILABLE AS TO WHAT ACTUALLY WAS GOING ON. THIS STUDY, AS FULLY ENROLLED, WILL CONTINUE FOR THE FORESEEABLE FUTURE. NEXT IS A SLIDE THAT DETAILS WHAT WE HAVE SEEN FOR WHAT IS GOING ON IN THE ACTIVE VACCINE TRIALS SO WHAT I HAVE HERE IS THE LISTING OF ALL THE ACTIVE TRIALS INCLUDING ACTIVE 2 AND ACTIVE 3 WHICH ARE PRIMARILY DRIVEN BY NIAID. IT'S IMPORTANT TO NOTE, THE ANTIBODY COMBINATION HAS REPORTED OUT ADHD. THE AZ COMPONENT COMPLETED THE PHASE 2 AND THE COMPANY HAS MOVED OVER WITH THEIR OWN PHASE 3. SEVERAL OF THE AGENTS, THE ONE LISTED THERE AS S.A.B., THE ROCK A FELLER BMS ANTIBODY COM COMBINATION AND THE THEY'RE NOW LOOKING TO SEE WHAT WILL MEET THE CRITERIA TO MOVE FORWARD TO PHASE 3 SO THAT IS THE STATUS -- THEY WERE TOLD EITHER FOR FUTILITY AND THEY ARE SEEKING TO BRING THE PFIZER P.I. ON WITHIN THE NEXT COUPLE OF WEEKS TO START THIS ANALYSIS OF THIS INHIBITOR. IT'S DIFFERENT THAN KAISER IS TAKING ON FOR OUT PATIENT. THIS REQUIRES CONTINUOUS INFUSION OVER FIVE DAYS. AND IN TERMS OF OTHER THINGS THAT ARE HAPPENING, ACTIVE 6 IS AN OUT PATIENT PHASE 3 MASTER PROTOCOL LOOKING AT REPURPOSED AGENTS AND IT LOOKS LIKE MONT. >> Kevin: MONT ELUCATL AND I'LL STOP THERE WITH ACTIVE. NEXT SLIDE, PLEASE. THE ON TE ANTIBODY FRONT NOT MUCH MORE TO REPORT. YOU CAN SEE THERE THAT THE E.U.A.s FOR LILLY REGENERON AND WE ADVANCE OTHER ANNIE ANTIBODIES. SO THE ONE OTHER POINT ABOUT THE AstraZeneca COMBINATION HAS BEEN SHOWN TO BE EFFECTIVE AS POST EXPOSURE PROFILAXIS AND THAT IS CONTINUING. THE DATA ON THE VACCINES CONTINUES TO EVOLVE. IT'S A VERY INTERESTING TIME BECAUSE WE HAVE THE INTERSECTION OF NEW VARIANTS OF CONCERN EMERGING AND WE HAVE VACCINE IMMUNITY WAINING AND HOW THOSE INTERSECT AND HOW THEY'LL TRANSLATE INTO THE NEED FOR BOOST IS AN OPENLY DEBATED SUBJECT. THE DATA OUT OF ISRAEL IS CRYSTAL CLEAR FOR THE PFIZER-BIONTECH THAT BOOSTING IS IN ORDER. SOME OF THE VACCINES ARE NOT QUITE AS CLEAR AND WE CONTINUE TO WATCH THIS. ULTIMATELY IT'S NOT A NIH DECISION. THE FDA WILL RULE WHAT IS HAPPENING WITH E.U.A.s AND THE ACIP AND OTHER COMMITTEES WILL COME ON AND HAVE RECOMMENDATIONS AS WE GO FORWARD. SO, I DON'T HAVE ANY PARTICULAR INSIGHTS INTO THIS OTHER THAN THE DATA YOU SEE THERE AND YOU CAN SEE WE'RE STILL LACKING IN E.U.A. SUBMISSION FOR THE AstraZeneca PRODUCT AS WELL AS A E.U. A FOR NOVAVAX AND THE SAN IF F PHASE 3 IS ENROLLING. THIS WAS A PROGRAM THAT WAS ANNOUNCED AT THE WHITE HOUSE IN JUNE AND WE'RE MOVING FORWARD WITH THIS. THE MONEY CAME FROM THE AMERICAN RESCUE PLAN. THIS IS A WHOLE OF NIH INVOLVING NIAID, NCAT AND OFFICE CALLED ORIP WHICH OVERSEAS ANIMAL MOLDS AND OTHER BIG EXPENDITURE ACTIVITIES WITHIN THE NIHOD FROM THE NIH. ASIDE, IN COLLABORATION WITH BARDA. NEXT SLIDE, PLEASE. THE PURPOSE OF THIS PROGRAM IS REALLY TO CATALYZE THE DEVELOPMENT OF NEW MEDS TO COMBAT CORONAVIRUS DISEASE AND PREPARE AGAINST OTHER PANDEMIC THREATS. SO CURRENTLY IT'S FOCUSED ON DIRECT ACTING ANTIVIRALS FOR CORONAVIRUS TREATMENT AND ALMOST THEN, THROUGH A TWO-PRONG STRATEGY, ADVANCE DIRECT ACTING ANTIVIRALS AGAINST OTHER PANDEMIC THREATS. SO THIS IS JUST A TOP-LINE MESSAGING. IT'S THE AMOUNT OF MONEY IS THERE. IT'S A FIVE-YEAR PROGRAM. LOOKING AT VIRUS FAMILIES AND EARLY SPIRALS THROUGH DEVELOPMENT AND THEN WE'RE LOOKING TO MOVE CURRENTLY THREE MOLECULES POSSIBLY A FOURTH FORWARD TO EUA OR NDA WITH BARDA. THE FIRST OF WHICH IS THE MERC INHIBITOR. ADDITIONALLY WE HAVE, ON THE STREET, AN ANTI VIRAL DRUG DISCOVERY CENTER FOA THAT APPLICATIONS ARE DUE IN ABOUT A MONTH AND THIS IS A VERY LARGE PROGRAM THAT WILL REALLY HELP BUILD CENTERS OF EXCELLENCE TO TARGET DRUG DISCOVERY AND DEVELOPMENT FOR SARS-CoV-2 BUT THESE OTHER SEVEN VIRUS FAMILIES AS WELL AS IN ADDITION WE PLAN TO SUPPORT OTHER PUBLIC-PRIVATE PARTNERSHIPS. SO, HERE IS A BREAKDOWN OF WHAT WE'RE SEEKING THROUGH THE AVID CENTERS TO ESTABLISH MULTI-INVESTIGATOR, MULTI-DISCIPLINARY DISCOVERY GROUPS WE WANT TO USE WITHIN THIS STRUCTURAL SYSTEMS METHOD DRUG TARGETS THAT ARE SHARED OR HAVE SOME DEGREES OF SIMILARITY SO WE CAN WORK TOWARDS BROAD SPECTRUM AS NEEDED AND ANTIVIRALS AND WE PLAN TO PROGRESS PROMISING CANDIDATES TO IND ENABLING WORK ON THE DEVELOPMENT SIDE, WE INTEND TO SUPPORT KEY CLINICAL EARLY CLINICAL AND NON CLINICAL STUDIES. FORM THESE PUBLIC-PRIVATE PARTNERSHIPS TO ADVANCE NEW MOLECULES AND CONTINUE THIS ROLE OF DERISKING DRUG CANDIDATES AND DRUG LEADS TO INDUSTRY CAN COME IN AND PICK UP AND RUN WITH THE LEADS. THERE'S A LOT OF DISCUSSION WHAT IS IN SCOPE AND WHAT'S NOT IN SCOPE. I'LL MAKE THE POINTS AGAIN, THIS IS FOR DIRECT ACTING ANTIVIRALS AND WE'RE LOOKING AT SMALL MOLECULES OR BIO THERAPEUTICS AND FUNDAMENTALLY, WE'RE LOOKING FOR SOMETHING THAT CAN BE DELIVERED IN THE OUT PATIENT SETTING. SO, IF YOU CONSIDER A PILL, A PATCH, SOMETHING THAT CAN BE INHAULED THAT WOULINHALED. IT'S OUT OF SCOPE IF IT REQUIRES A INJECTION OR INFUSION. THE VIRUS FAMILIES ARE LISTED THERE. AND WE, AGAIN, AS A TWO-PRONG DETECT, THE LONG-TERM GOAL IS TO DISCOVERY THROUGH EARLY PHASE 1 CLINICAL TRIALS WITHIN THE SCOPE OF APP WITH A GEL TO PARTNERING AND MOVING MOLECULES OFF TO INDUSTRY AND IN THE SHORT TERM, WE ARE WORKING TO MOVE AND COLLABORATION WITH BARDA, THREE MOLECULES TOWARDS EUA OR NDA. NEXT SLIDE, PLEASE. THESE ARE THE FAMILIES AND AGAIN YOU CAN SEE WE LIST SOME OF THE VIRUSES THERE AND WE CHOSE WELL. THE ONLY ONE THAT CURRENTLY HAS SUPPORT WITHIN THE PROGRAM FOR LATE-STAGE CLINICAL DEVELOPMENT ARE SARS-CoV-2 ANTI-SARS-CoV-2 AGENTS. NEXT SLIDE, PLEASE. SO, I'LL CLOSE BY REMINDING EVERYBODY THAT AS WE HAVE A MEETING SCHEDULED. I HOPE THESE ARE ALL ON YOUR CALENDER. AND AS KEN REMINDED YOU, WHEN WE HAVE THE JANUARY 31st ARAC MEETING, THIS WILL BE A VIRTUAL MEETING AND WE HOPE THAT MAYBE, JUST MAYBE, BY JUNE WE WILL BE BACK IN BUSINESS IN BETHEZDA. TIME WILL TAKE TO GET BACK TO NORMAL. WHATEVER NORMAL WILL BE WHEN WE COME BACK. I'LL STOP THERE AND TAKE QUESTIONS. THANK YOU FOR THAT OVERVIEW. WE HAVE SOME TIME FOR DISCUSSION. >> THAT WAS GREAT AND WHAT I WANT TO ASK ABOUT WAS MY IMPRESSION HAD BEEN IT WAS LIKE MORE PRIVATE AND I WAS REALLY EX SIGHTEEXCITED ABOUT THAT DRUG AND I KNOW YOU SAID Dr. SMITH ROTATED OFF, BUT. >> THERE'S ARE PRESENTATIONS THAT ARE GOING TO BE AT ABOUT THE DOSE SELECTION AND WHAT HAS GONE INTO THE DRUG AND I'VE SEEN THE DATA. IT'S RELATIVELY PROMISING. THE INTENTION IS OVER THE FALL, MERC WILL FILE A 4EUA AND THEN DEPENDING ON HOW THAT DATA LOOKS, THERE WILL BE AN ARRANGEMENT WITH BARDA AND MERK TO MOVE FORWARD TO MAKE THAT AGENT AVAILABLE. HOPEFULLY WITHIN Q4 OF 2021. SO THIS FALL. THAT'S WHAT WE WANT. IT HAS TO BE SUCCESSFUL IN ITS TRIAL. THIS IS ALL PREDICATED ON THE ANTIVIRAL ACTIVITY THAT'S BEEN REPORTED. NOT JUST WHAT IS AT I.D. WORK WAS IN THE HETERO TRIAL THAT CAME OUT OF INDIA, THAT ACTUALLY LOOKED GOOD. WE'LL SEE HOW THAT GOES. THAT'S THE PROMISE, WE'LL SEE HOW THAT GOES. >> I KNOW THE GOVERNMENT HAS PURCHASED -- >> IT HASN'T YET. >> OK. [LAUGHTER] >> THAT'S EXACTLY THE PLAN. IS THAT THERE WILL BE A BUY, IF IT'S SUCCESSFUL. >> YEAH. >> THAT MAKES SENSE, OF COURSE. >> THANK YOU. >> WE DON'T WANT TO BUY A BROKEN TOASTER. >> OK. [LAUGHTER] ANY ANOTHER QUESTIONS? >> I'LL ASK A QUESTION IF YOU HAVE A MOMENT. THANK YOU FOR THIS UPDATE. I'M VERY EXCITED ABOUT THE ADVANCES IN THE SCIENCE AND LET ME KNOW IF THIS IS OUTSIDE OF YOUR PURVIEW. IS THERE ANYTHING SPECIFIC AND TARGETED COMING OUT OF THE GOVERNMENT TO ADDRESS VACCINE HESITANCY IN OUR COUNTRY? I THINK THAT LEADERS OF THE DIVISION OF AIDS HAVE -- THERE'S BEEN ENORMOUS EFFORT TO OUTREACH OF THE IT'S AN ENORMOUS EFFORT. I MEAN I DO SEE THE TALKS, THE PRESENTATION, THE TOWN HALLS, ET CETERA. ARE THERE OTHER COORDINATED ON GOING EFFORTS TO TACKLE TO BETTER UNDERSTAND AND TO TRY AND TACKLE THIS ISSUE BECAUSE YOU KNOW, THE GREATEST SCIENCES ONLY ARE GOING TO GET US JUST SO FAR IF PEOPLE ARE NOT AWARE OF IT OR DON'T TRUST IT OR HAVE REASONS TO DISCOUNT IT, ET CETERA. SO I'M CURIOUS TO KNOW IF THERE'S SOMETHING GOING ON SPECIFICALLY IN THAT RAIN LANE. >> THERE IS SO MUCH GOING ON IN THAN THIS LANE, SOMETIMES I WORRY THAT IT'S LIKE ONE OF THOSE WAVE -AND WE'RE CANCELLING EACH OTHER OUT A LITTLE BIT. EVERYBODY, IT'S LIKE ALL OARS ARE IN THE WATER ROWING IN THE MAXIMUM EXTENT WE K WE'RE UP AGAINST FOES THAT OCCUPY INFLUENCE OR STATUS ON Facebook AND OTHER PLACES. AND YOU KNOW, JUST WE HAVE TO CONTINUE TO PROMOTE THE TRUTH. I MEAN, I THINK PRESIDENT JOE BIDEN SAID IT WELL, WE TRIED PERSUASION, NOW WE'RE GOING TO TRY REQUIREMENT. AND SEE WHAT WE CAN DO. WE'VE ALL READ ABOUT PREVIOUS OUTBREAKS AND THE NEED TO DO THIS THING. VACCINE HESITANCY IS NOT A NEW THING. APPARENTLY GEORGE WASHINGTON WENT THROUGH THIS WHEN HE WAS TRYING TO VACCINATE THE TROOPS AGAINST THE REVOLUTIONARY WAR AGAINST SMALLPOX. HE CON VA LESSED AND HE WAS THE FIRST EXAMPLE OF SOMEONE WHO SAID I'M GOING TO MANDATE VACCINATION FOR THE TROOPS. THIS IS A COLLABORATION WITH OTHER PARTS OF NIH TO DEAL WITH VACCINE HESITANCY AND THE BEHAVIOR AROUND IT. TO ME, WE REALLY NEED BEHAVIORAL AND SOCIAL SCIENTISTS TO STUDY THIS. THERE'S A LOT GOING ON IN THIS, BUT I'M NOT INVOLVED IN ANYTHING FORMAL. IT'S A LONG ANSWER TO YOUR QUESTION. >> I HOPE THERE WILL BE MORE ON GOING COORDINATED STRATEGIC EFFORTS TO TRY TO ADVANCE FACTUAL, SCIENTIFIC INFORMATION IN A WAY THAT IS DIGESTIBLE TO THE AVERAGE AMERICAN SO THAT WE CAN IDENTIFY AND UNDERSTAND IT AND UNDERSTAND HOW IT RELATES TO OUR OWN SPECIFIC SITUATION. >> I AGREE WITH YOU COMPLETELY AND IT IS SO CONFUSING WHEN -- THE CHALLENGE WE FACE, THIS IS SO FAST-MOVING. WE GET TO JULY 4 AND THE IT LOOK 4 AND IT LOOKSLIKE SWEETNESS AND LIGH T AND DELTA COMES AND CHANGES EVERYTHING. WE'RE STILL ADJUSTING TO THAT. AND THEN THE BUSINESS WITH IMMUNITY WAINING AND ALL THESE OTHER THINGS, HOW DO YOU KEEP EVERYBODY INFORMED, IN THE MEANTIME, WHEN, I DON'T KNOW, IT'S REALLY A CHALLENGE AND I APPRECIATE WHAT YOU ARE SAYING AND WE'LL CONTINUE TO PUSH AND PUSH AND PUSH ON THIS. FOR EXAMPLE, ONE OF THE THINGS THAT I AM REALLY INTERESTED IN IN IS WHAT WE NEED TO GET OUT FAST ON THE MEDICATIONS IF AND WHEN THEY COME OUT IN Q4. WE DON'T WANT DRUG HE IS SANTEE ON TOP OF VACCINE HESITANCY SO WHAT CAN WE DO AHEAD OF TIME, SHOULD THEY MAKE IT OUT. THAT'S THE KIND OF THING THAT I'M THINKING ABOUT. >> HOW DOES ALL THIS WORK WITH THE FLU SHOT? >> WE'RE ALL SUPPOSED TO GET OUR FLU SHOT. NIH IS LAUNCHING THE FOIL THE FLU PROGRAM NEXT WEEK AND SO -- THE GOOD NEWS I GUESS ABOUT FLU IS IT HAS BEEN NONEXISTENT IN THE SOUTHERN HEMISPHERE AGAIN THIS YEAR. I DO WANT -- AUDREY PUTS A GOOD POINT IN THE NOTE, IN THE CHAT, THAT WE WANT PEOPLE TO TAKE REAL DRUGS NOT UNAPPROVED ONES. WE'LL SEE WHAT WE DO. >> MELISSA, THANK YOU FOR BRINGING THAT REALLY IMPORTANT POINT UP. WE'RE ALL TRYING TO WORK ON THAT AND CERTAINLY CARL, AS YOU SAID, THERE ARE OTHER INSTITUTES AS WELL THAT BEHAVE THAT WAY IN SOCIAL SCIENCE. >> WE NEED A PARTY ON THIS. WE NEED PEOPLE TOGETHER. >> ABSOLUTELY. THANK YOU. ALL. WE'RE GOING TO MOVE ONTO THE ORAC UPDATE AND WE WANT TO OPEN TO GET READY TO OPEN YOUR ELECTRONIC COUNCIL BOOKS BECAUSE AS WE GO TO THE CONCEPT WE'LL NEED TO HAVE THOSE AND VOTING ON THOSE AND TRISH, THANK YOU VERY MUCH. >> THANK YOU SO MUCH. SO, THIS IS JUST A LITTLE BIT OF THE AGENDA THAT WE'RE GOING TO TALK ABOUT TODAY. SO, WE HAVE THE OAR DIRECTOR'S REPORT AND NIH UNITE OVERVIEW. AGAIN, WE HAD THE HIV ANTIRETROVIRAL WORKING GROUPS REPORTED OUT. WE HAD A DISCUSSION ON PHARMA CODE GENETICS AND ANTI-RETRO VIRALS AND THE IMPORTANCE OF INCLUSIVITY IN SCIENCE AND A NICE UPDATE FROM THE WHITE HOUSE. WE HAD COVID RELATED RESOURCES AND CDC, SURVEILLANCE DATA, AND OAR ENGAGEMENTS, WHICH YOU CAN SEE HIGHLIGHTED HERE AS WELL AS THERE WERE SOME RESENT OAR LISTENING SESSION AND THESE WERE IN NEBRASKA, SAN DIEGO AND NEW ORLEANS. SO, OAR IS RECENTLY HELD A SERIES OF FOUR ADDITIONAL LISTENING SESSIONS AND THEN THESE WERE REALLY FOR EARLY CAREER HIV INVESTIGATORS. SO PROMOTING THE NEXT GENERATION HIV RESEARCH AND INVESTIGATORS IS ONE OF THE TOP PRIORITIES OF OAR AND REALLY THEY WANT TO ENSURE AT LEAST 5% OF HIV GRANTEES EACH YEAR ARE EARLY CAREER INVESTIGATORS. WHICH IS PREPORTIO PROPORTIONAL TO THE OVER ALL IN NIH. AND IMPORTANT THINGS THAT SURFACE DURING THESE SESSIONS RELATED TO MENTOR, PEER REVIEW, FUNDING MECHANISMS, NETWORKING, COMMUNITY AND THE IMPACT OF COVID-19. SO, OAR ALSO CONVENED A VIRTUAL EXPERT PANEL THAT YOU CAN SEE HERE. AGAIN, THEY LOOKED AT THESE CHARGES THAT ARE FACED IN EARLY RESEARCHERS. AT THE INSTITUTIONAL LEVEL AND IDEAS TO INCREASE THEIR DIVERSITY AND SUPPORT BOTH INSTITUTIONAL AND NIH LEVEL. SOME OF THESE THINGS WERE INCREASED FLEXIBILITY AND FUNDING MECHANISMS, ENHANCE SUPPORT FOR LOWER RESOURCED INSTITUTIONS AND ENHANCE SUPPORT FOR MENTORING ACTIVITIES AND EXPAND AND ACCESS TO EXISTING NIH-HIV NETWORKS AND RESOURCES AND ADDRESSING ISSUES IN PEER REVIEW TO FAIRLY EVALUATE EARLY CAREER APPLICANTS AND INSENT SIN TA VICE RESEARCH IN NIH. AS 49th ANNIVERSARY OF THE 1981OAR DEVELOPED COMMUNICATION CAM PINED THAT WILL CONTINUE THROUGH WORLD'S AIDS DAY DECEMBER 1st AND INFORMATION CAN BE FOUND ON O.A.R.'S WEBSITE. SO Dr. GOOD AND I HIGHLIGHTED THE $3.1 BILLION FY2021 RESEARCH BUDGET AND NOTED THE FY2022 BUDGET INCLUDES $3.1 BILLION BY NIH-HITCH RESEARCH. AND AGAIN, ADDITIONAL INFORMATION CAN BE INCLUDED ON THE WEBSITE AND THIS WAS RELEASED IN EARLY JUNE. SO, IF YOU CAN BACK ONE. ANOTHER THING IS THAT THE NIH-AIDS PORTFOLIO IS NOW ALMOST 100 PERCENT ALIGNED WITH THE OVER ARCHING PRIORITIES. NIH-HIV RESEARCH FUNDING HAS INCREASED MODERATELY OVER THE PAST 20 YEARS. RECENT BUDGET INCREASES HAVE LED BEHIND THE INCREASES COST WITH CONDUCTING RESEARCH. SO, WE ALSO HAD TWO PRESENTATIONS ON THE HIV UNITE INITIATIVE WAS ESTABLISHED TO IDENTIFY AND ADDRESS STRUCTURAL RACISM WITHIN NIH SUPPORTED IN THE GREATER SCIENTIFIC COMMUNITY FOLLOWED BY Dr. GOODMO REMARKS. THEY DESCRIBED THE GENESIS OF UNITE. THE INITIAL RECOMMENDATIONS AND ACTIONS AND PRIORITIES MOVING FORWARD. AS WELL AS AN OVERVIEW OF THE E, WHICH IS EXTRAMURAL COMMITTEE. THE UNITE E COMMITTEE IS CHARGED WITH PERFORMING A BROAD SYSTEMATIC EVALUATION OF NIH. EXTRAMURAL POLICIES AND PROCEDURES TO IDENTIFY CHANGES AND PRACTICES IN STRUCTURES THAT PERPETUATE LACK OF INCLUSIVITY AND DIVERSITY WITHIN THE EXTRAMURAL RESEARCH PROGRAM. THIS INCLUDES DEVELOPING STRATEGIES TO ADDRESS FUNDING DISPARITIES AND INCREASE APPLICATIONS THAT WOULD SUPPORT INDIVIDUALS FROM UNDER REPRESENTED GROUPS. THEY HAD GUIDELINES UPDATED IN JUNE. THE PEDIATRIC GUIDELINES IS REVIEWING NEW DATA AND IMPLICATIONS REDUCING THE USE OF MILLION DRUGS IN ADOLESCENCE. ALSO THE PERINATAL GUIDELINES AND ADDRESSING THE CARE OF TRANSGENDER AND NON BINARY PEOPLE WHO ARE PREGNANT OR TRYING TO CONCEIVE. IN THE PEDIATRIC OPPORTUNISTIC GUIDELINES UNDER A RESCOPING EXERCISE WHICH IS GOING TO BE DETAILED IN THE OCTOBER MEETING. AND AGAIN, MORE SPECIFICS CAN BE FOUND IN THE MINUTES THAT ARE POSTED ON THE OAR WEBSITE. SO, Dr. BUMKISS, A PROFESSOR AND CHAIR OF PHARMACOLOGY AND POLL HE CAMOLECULAR DISCUSSED RYE SEARCH WITH PHARMA CO GENETICS AND ANTI-RETRO VIRALS AND INCLUSIVEY AND SCIENCE. Mr. PHILLIPS DISCUSSED AIDS IN 1981 AND KEY 2020 AND THE HIV EPIDEMIC, ACCOMPLISHMENTS IN THE AMERICANS HIV EPIDEMIC ANALYSIS DASHBOARD. HE ALSO DISCUSSED MINORITIES AND HIV FUNDING ACTIVITIES, PRIORITIES INCLUDING UPCOMING REVISIONS TO THE NATIONAL STRATEGIC PLAN AND TO REFLECT THE ADMINISTRATIONS PRIORITIES INCLUDING EQUITY, ELIMINATION OF STIGMA AND DISCRIMINATION AND ACCESS TO HEALTH COVERAGE. SO AS A REMINDER, OARAC'S MEETING MINUTES AND LINKS TO THE VIDEO CASTS ARE ON THEIR WEBSITE. WITH THE OAR WEBSITE AND THE NEXT MEETING IS OCTOBER 28th OCTOBER 28th AND AGAIN THIS WILL BE VIRTUAL AND GUEST SPEAKERS WILL INCLUDE THE CDC DIRECTOR AND ENCORE APPEARANCE FROM Mr. PHILLIPS. AND THAT IS IT. THANK YOU. >> GREAT, THANK YOU Dr. BURDO. QUESTIONS ABOUT ORAC ISSUES? ANY QUESTIONS THAT PEOPLE HAVE? MONICA. >> I THOUGHT THAT WAS GREAT. THE CONVENING OF A COMMITTEE TO SUPPORT EARLY STAGE INVESTIGATORS. MY QUESTION WAS, WAS THAT DISH COULDN'T TELL BY THE SLIDE. WAS THAT SPECIFICALLY FOR EARLY CORE INVESTIGATORS FROM UNDER REPRESENTED MINORITIES? >> SO, NO. THAT WAS TWO DIFFERENT THINGS. SO THEY HAD DISCUSSION PANELS ON JUST EARLY-STAGE INVESTIGATORS IN GENERAL AND THEN THERE WAS OTHER INITIATIVES TO LOOK INTO DIVERSITY AND OTHER REPRESENTED MINORITIES SO, NO, THAT WAS NOT. >> THANK YOU. >> ANY OTHER QUESTIONS? ALL RIGHT. THANK YOU, AGAIN, THAT WAS GREAT. WE NOW HAVE FOUR CONCEPTS THAT WE WILL GO OVER. AND SO AGAIN I'LL ASK EVERYONE TO OPEN THEIR ECBs AND WE WILL PRESENT THESE ONE AT A TIME AND THEN VOTE ON THEM. THE FIRST ONE, PRESENTED BY Dr. AMY PALIN, A MULTI-OMICS APPROACH TO IMMUNE RESPONSES IN HIV VACCINATION AND INTERVENTION. Dr. PALIN. >> GOOD AFTERNOON. EVERYONE. I AM AMY PALIN, I AM A PROGRAM OFFICER IN THE VACCINE RESEARCH PROGRAM PRESENTING ON BEHALF OF THE NUMBER OF COLLEAGUES AND DEEDS, NOVAK AND BRIDG BRIGITTE SANDERS ACROSS THE BASIC SCIENCES PROGRAM AND TRANSLATIONAL RESEARCH PROGRAM AND VACCINE RESEARCH PROGRAM. THIS FUNDING CONCEPT IS TITLED A MULTI-OMICS APPROACH TO IMMUNE RESPONSES IN HIV VACCINATION AND INTERVENTION. IT'S A NEW P01. THE CONCEPT IS INTENDED TO SUPPORT INTEGRATION OF BIO-INFORMATICS AND HYPOTHESIS DRIVEN AND IN ORDER TO DEFINE SIGNATURES OF OUTCOMES OF HIV AND VACCINATION OR INTERVENTION. THE FIRST YEAR TOTAL COST IS $4 MILLION WITH A CAP ON DIRECT COSTS OF $1 MILLION. WE HAVE POTENTIAL CO FUNDING FROM NIAID. THIS CONCEPT GREW OUT OF A WORKSHOP ORGANIZED IN 2020 BY DAIDS ON NEXT GENERATION TECHNIQUES AND ASSAYS. WE HAVE A CONCEPT WHERE SAMPLES FROM CLINICAL TRIALS, NON HUMAN PRIMATES WILL BE INTERROGATED WITH A NUMBER OF OMICS AND IN THE EXAMPLE I'M SHOWING HERE. PROTECTIVE AND NON PROTECTIVE SIGNATURES OF VACCINATION AND OTHER INTERVENTIONS. NOW, THIS IS REALLY AN ITERATIVE PROCESS WHEREBY THESE SIGNATURES CAN THEN BE VALIDATED AND THE APPROPRIATE MODEL USING OMICS OR A MORE TARGETED APPROACH. AND WE REALLY WANT TO DRIVE GENERATION OF THE NEXT GENERATION OF VACCINES AND THERAPEUTICS. FROM THE WORKSHOP, WE IDENTIFIED A NUMBER OF INCLUDING A MAJOR GAP IN THE ABILITY TO PRO DICTIONARPREDICTEFFICACY AND OTHER INTERVE NTIONS AND THERE ARE A NUMBER OF FACTORS CONTRIBUTING TO THIS INCLUDING THE TREMENDOUS DEGREE OF IMMUNE HETEROGENEITY. WE WANT TO ENABLE VALIDATION AND APPLICATION OF COMPUTATIONALLY GENERATED HYPOTHESIS SO GENERATION OF BIOLOGICALLY MEANINGFUL INSIGHTS FROM BIG DATA AND THEN VALIDATION OF THOSE IN THE APPROPRIATE MODELS WHETHER THAT'S AN INVITO MODEL, ANIMAL MODEL OR HUMAN SAMPLES. TO THAT END, WE THINK IT'S IMPORTANT TO IMPROVE THE PREDICTIVE VALUE OF MODELS AND FROM DISCUSSING GAPS WITHIN INVESTIGATORS, THERE'S A REAL NEED TO INTEGRATE DATA ACROSS OMICS PLATFORM SO EVEN WITHIN THE SAME TECHNOLOGY ACROSS MODELS AND BETWEEN SPECIES. WE ARE SUPPORTING THE OMICS APPROACH BECAUSE IT'S RELATIVELY UNBIASED. I THINK WE'VE BEEN HEARING A LOT IN TALK OF SARS-CoV-2 VACCINES THAT CORRELATES A PROTECTION MAY NOT BE MECHANISTIC, THEY MAY BE SURROGATE AND SO WE THINK THAT THAT UNBIASED APPROACH WILL ENABLE DETECTION OF THAT MORE EASILY. I'M GOING TO SHOW YOU THREE EXAMPLES OF THE TYPES OF RESEARCH THAT WE'RE SEEKING TO SUPPORT. THIS IS AN EXAMPLE FROM THE AD26 FLA26PLATFORM THAT CARL DISCUSSED EARLIER USING BOOST AND THIS LAID THE GROUNDWORK FOR THE HVTN705 AND 706 TRIALS AND WE'LL ALL HEARD AND THEY DID NOT MEET THE EFFICACY CRITERIA BUT THERE WAS AND 26% EFFICACY AND AND I'LL MENTION THAT WE'RE ACTIVELY PLANNING THE CASE CONTROL ANALYSIS AND AND I REALIZE IT'S A VERY SLIDE WHAT I REALLY WANT TO HIGHLIGHT HERE JUST TREMENDOUS VARIATION IN IMMUNE RESPONSES TO THE SAME STIMULUS IN THIS CASE AN HIV VACCINE. HERE WE'RE LOOKING AT INTER FUR AN GAMMA RESPONSES AND YOU CAN SEE THERE'S VERY HIGH RESPONDERS AND SOME NON RESPONDERS. SO, THIS IS ALSO TRUE ACROSS MANY MEASURES OF IMMUN IMMUNO GENICITY. WE I THINK THEY CAN HELP UNDERSTAND THE DIFFERENCES IN THESE RESPONSES AND PERHAPS EVEN PREDICT WHICH INDIVIDUALS MIGHT RESPOND TO A VACCINE OR UNCOVER, AS I MENTIONED, SIGNATURES OF EFFICACY. SO HERE WE HAVE A HIGHLY HETERO GENIOUS RESPONSE TO THE SAME STIMULUS AND OMICS CAN HELP US UNDERSTAND AND UNPACK THAT. THE NEXT EXAMPLE IS THE WORK OF THE INFLUENZA VACCINATION. AS I JUST SHOWED YOU FOR THE HIV VACCINE, THERE IS A HUGE VARIATION IN IMMUNE RESPONSES TO INFLUENZA VACCINATION. IN THIS CASE, THEY TOOK INDIVIDUALS WHO HAD RECEIVED TRIVALENT AND PROVIDE MACRO ANALYSIS AND THEIR PBMCs AND FOUND THAT GENE EXPRESSION OF THE ANTIBODY TIGHTERS AND THEY'RE PROTECTION FOR INFLUENZA. SO THEY DEVELOPED THE HYPOTHESIS THAT GUT MICRO BIODA WERE ACTING AS AND ENGAGING TLR5. SO, IT MOVED INTO THE MOUSE MODEL TO VALIDATE THIS AND WHAT I'M NOT SHOWING IS THAT TLR5 KNOCK OUT MICE HAVE VERY LOW ANTIBODY RESPONSE TO INFLUENZA VACCINATION AND GERM FREE MICE, ALSO HAVE VERY LOW ANTIBODY RESPONSES. HERE THEY SHOWED THAT ANTIBIOTIC TREATMENT TO THE GUT MICRO FLORA REDUCED THE ANTIBODY RESPONSES INFLUENZA VACCINATION. AND THAT ADDITION OF FLUGELLIN RESTORED THAT RESPONSE. THEY TOOK THIS BACK INTO HUMANS AND PERFORMED A CLINICAL TRIAL WHERE INDIVIDUALS WITH LOW PREEXISTING INFLUENZA TIE TERSE DEVELOPED NEW NEUTRALLATION TITERS TO INFLUENZA SO TWO THINGS I'D LIKE ABOUT THIS SERIES OF EXPERIMENTS. ONE IS THEY TOOK AN OBSERVATION IN HUMANS AND MOVED INTO MICE AND THEN BACK INTO HUMANS. AND THE OTHER IS THAT AN OMICS APPROACH, NOT A GENERATION OMICS APPROACH FOUND AN UNEXPECTED CORAL AT THAT IN THIS CASE DID TURNOUT TO BE MECHANISTIC WHERE THE MICRO BIODA WERE STIMULATING TLR5 TO IMPROVE VACCINE RESPONSES. THE LAST EXAMPLE IS THE WORK THE LOUIS PICKER AND THE CMV VECTOR. AND WITH THIS IN THE PRE CLINICAL WORK, THEY FOUND THAT THE RECENT CMV/SIV HAD A EFFICACY AGAINST CHALLENGE SO 55% OF THE ANIMALS WHO RECEIVED THIS WERE PROTECTED FROM CHALLENGE. THIS WAS TRUE REQUEST ADMINISTRATIONS. WORKING WITH THE NON HUMAN PRIMATE GENOMICS CORE THEY IDENTIFIED AN IL15 SIGNATURE THAT WAS UP REGULATED AFTER IMMUNIZATION AND SUSTAINED IN THE PROTECTED ANIMALS. AND THIS SIGNATURE COULD IN FACT BE USED TO PREDICT WHICH ANIMALS WOULD BE PROTECTED. SO THIS WAS REALLY A SIGNATURE ADVANCE IN IDENTIFYING A SIGNATURE THAT COULD ACTUALLY PREDICT PROTECTION FROM SIV CHALLENGE. SO, WITH THOSE EX POLLS, I'M TUREXAMPLES, I'LLTURN TO THIS CON ZEST. THIS IS PL1 SO IT REQUIRES TWO OR MORE PROJECTS. INVESTIGATORS HAVE THE DISCRETION AND FREEDOM FOR MORE PROJECTS AND MORE CORES AS NEEDED. WE REQUIRE HIV RESEARCH AND ALLOW COMPARISON TO OTHER PATHOGENS. THIS CONCEPT IS NOT INTENDED TO BE EXPLORATORY SO WE DO REQUIRE PRELIMINARY DATA FOR VACCINES THERAPEUTIC OR IMMUNO MODULATORY AND THIS IS THE DEFINED AS EVIDENCE OF EFFICACY AND SMALL ANIMAL MODELS OR IN HUMANS. WE REQUIRED USE OF AT LEAST TWO OMICS APPROACHES. THERE'S AN EXPERIMENTAL COMPONENT AND A COMPUTATIONAL COMPONENT REQUIRED. WE'VE CHOSEN TO ALLOW INVESTIGATORS TO HAVE THOSE PRESENT EITHER AS A PROJECTOR A CORE TO PROVIDE FLEXIBILITY AND WEAR ALONG THAT PATHWAY OR STAPLE THAT I SHOWED EARLIER DESCRIBING THE WORKSHOP. WHERE IS MOST APPROPRIATE FOR THAT PROJECT. WE ANTICIPATE RECEIVING APPLICATIONS THAT INVOLVE WORK WITH HUMANS, NON HUMAN PRIME IT'S A AND SMALL ANIMAL MODELS IS PRO PRE A CLINICAL TRIALS ARE NOT ALLOWED BUT WE DO HIGHLY ENCOURAGE WORK WITH ARCHIVE SAMPLES FROM CLINICAL TRIALS OR ANCILLARY STUDIES FROM TRIALS THAT ARE FUNDED ELSEWHERE. THERE'S OUR WEALTH OF SAMPLES AVAILABLE AND WE WANT TO ENCOURAGE INTERROGATION OF THOSE. THIS CONCEPT ENCOMPASSES PREVENTATIVE AND THERAPEUTIC VACCINES AND IMMUNO MODULATORY AND TREATMENT INTERSECTION AND TREATMENT INTERRUPTION IS ALSO ALLOWED. I HAVE DESIGNED OMICS APPROACH HERE'S AND THIS IS NOT COM COMPREHENSIVE. CLINICAL TRIALS ARE NOT ALLOWED UNDER THIS P01. WE'RE NOT INTENDED TO STUDY RESPONSES TO INITIAL OR ESTABLISHED INFECTION IN THE ABSENCE OF AN INTERVENTION OR A VACCINATION. SMALL MOLECULE ANTIRETROVIRAL THERAPEUTICS ARE NOT ALLOWED AND I HAVE COVERED THE REST OF THIS ELSEWHERE. WE THANK Dr THE DOCTOR IN ORDER TO REFINE AND IMPROVE IT WITH FEEDBACK. THEY WERE HIGHLY SUPPORTIVE. SAYING I THINK THIS INITIATIVE IS TIMELY AND NEEDED AND I FULLY SUPPORT IT MOVING FORWARD. WE RECEIVED THE FEEDBACK TO STRENGTHEN THE LENGTH BETWEEN HUMAN AND ANIMAL DATA AND WE COMPLETELY DEGREE WITH THAT AND WE THINK IT WILL REALLY HELP IN IMPROVING THE PREDICTIVE VALUE OF VARIOUS MODEL AND GENERATING MEANINGFUL INSIGHTS SO WE'LL MAKE SURE TO EMPHASIZE THAT WHEN WRITING THE RSA. WE WERE ASKED TO CONSIDER OPTIONS FOR GREATER FLEXIBILITY IN THE PO1 AND TO ALLOW INVESTIGATORS TO ADDRESS ANY EXCITING ADVANCES IN THE HIV VACCINES FIELD. FLEXIBILITY IS LIMITED BY NIH GRANT POLICY AS WELL AS THE REQUIREMENT FOR A PEER REVIEW AND SO INVESTIGATORS WILL BE ENCOURAGED TO DISCUSS THEIR OPTIONS WITH THEIR PROGRAM OFFICERS IN ORDER TO DETERMINE WHAT IS IN SCOPE, WHAT MAY REQUIRE A REVISION OR A NEW GRANT APPLICATION. AND THAT BRINGS ME BANG TO THE CONCEPT SLIDE. WITH THAT, I THANK YOU FOR YOUR ATTENTION AND I AM HAPPY TO TAKE QUESTIONS. >> THANK YOU, THAT WAS A GREAT PO1 OPPORTUNITY. QUESTIONS? >> I GUESS I SHOULD HAVE ASKED THIS BEFORE. IT WOULD BE HELPFUL TO HAVE A SMALL CLINICAL STUDY AS YOU POINTED OUT, THE GROUP SHOWED THAT THAT WAS EXTREMELY USEFUL IS THERE A REASON? IS IT JUST THIS GRANT MECHANISM THAT DOESN'T ALLOW THAT? >> IT'S A COMBINATION OF TWO THINGS. ONE IS THAT BUDGETARY. WE WERE CONCERNED A CLINICAL STUDY MIGHT TAKE UP TOO MUCH OF THE BUDGET AND THE OTHER IS THAT WE REALLY INITIATED THIS THINKING, OK, HOW CAN WE TAKE ADVANTAGE OF THE RESOURCES WE ALREADY HAVE, FOR EXAMPLE, ALL OF THE EXISTING SAMPLES THAT THE HBTN OR OTHER NETWORKS MAY HAVE. >> ANY OTHER QUESTIONS? >> I JUST HAVE A QUESTION. THIS IS GREAT, SO EXCITING. VACCINES ARE THE BEST. I DO HAVE A QUESTION -- >> I AGREE. >> THIS IS PURELY TO DEFINE THOSE OUTCOME MEASURES, RIGHT? HOW WE WOULD LATER IDENTIFY OUTCOMES OF RESPONSE? IS THAT ACCURATE? >> NO, I THINK WE WERE INTERESTED IN ALSO MINING SOME 6 THE ROYALS THAT HAVE ALREADY OCCURRED, FOR EXAMPLE, WHERE WE SAW SEVEN OR FIVE AND HOW WE CAN LOOK AT THOSE IN A THOROUGH AND DETAILED MANNER AND SEE IF WE CAN IDENTIFY WHO MAY HAVE BEEN PRE TACTED RATHER AND WHO WASN'T. I THINK THAT IS REALLY WHAT OUR THOUGHT WAS TO FOR THE TRIALS AND HOW WE CAN USE THAT TO IMPROVE THE NEXT GENERATION. SAY WE SAW A CYTOKINE SIGNATURE. >> THANK YOU AND VACCINES ARE GREAT. D.A.,s WE HEARD ARE GOOD SO WITH THE REST, YOU USE THE BEST CAUTIOUSLY. WE'RE NOT COMPARING. WE'RE TRYING TO SYNERGIES THE EFFORTS ACROSS THE BOARD HERE. ANY OTHER QUESTIONS, OF COURSE? WELL, THANK YOU Dr. PALIN. THAT WAS GREAT. GO TO THE ECBs AND VOTE AND SAVE YOUR VOTE, PLEASE. WE SHOULD HAVE PASSWORDS IN THE LIKE E-MAIL TO YOU. I WILL GIVE PEOPLE A MOMENT TO DO THAT. SUPER. WHY DON'T WE MOVE TO OUR NEXT PRESENTATION ON THE MOLECULAR DYNAMICS OF HIV AS THOSE SLIDES COME UP. WE LOOK FORWARD TO HEARING FROM Dr. DAVID MACDONALD. THERE HE IS. GREAT, SO LET ME TURN IT OVER TO YOU, DAVID. >> HI, EVERYBODY. GOOD AFTERNOON. I'M PRESENTING FROM THE BASIC SCIENCES PROGRAM WHERE I'M A PROGRAM OFFICER. AN INITIATIVE CONCEPT MOLECULAR DYNAMICS OF HIV. AND THERE'S MY SLIDES. SO, THE PURPOSE OF THIS INITIATIVE, THIS IS AN RO1 INITIATIVE. A SINGLE RFA IS WHAT WE'RE PROPOSING. TO FUND THREE TO FIVE INNOVATIVE RO1s SUPPORTING THIS STRUCTURAL COMPUTATIONAL AND FUNCTIONAL STUDIES OF KEY DYNAMIC PROCESSES THAT OCCURRED DURING THE HIV LIFE CYCLE. SO, MOLECULAR DYNAMICS IS A COMPUTATIONAL, COMPUTER COMPUTATION ALF THE MOVEMENT OF INDIVIDUAL ATOMS AND MOLECULES OVER TIME AND IT PROVIDES TESTABLE MODEL OF COMPLEX MOLECULAR BEHAVIOR SO IT CAPTURES THE MOVEMENT OF PROTEINS AND OTHER MOLECULES AT FINE TIME SCALES. AND IT CAN SIMULATE A LOT OF BIO MOLECULAR FUNCTIONS LIKE CONFIRMAL AND COMPLEX CELLULAR PROCESSES LIKE MEMBRANE FUSION OR SCISSION AND PROVIDES TESTABLE HYPOTHESIS THAT CAN DRIVE UTTER A TIVE STRUCTURAL ANALYSIS. THESE COME FROM OUR HIV GRANTEES AND THEY'RE HIGH RESOLUTION STRUCTURES AND IN THE ATOMIC LEVEL UNDER RESOLUTION OF COMPLEX MOLECULAR MACHINES. THIS ONE YOU MIGHT RECOGNIZE IS FOUR DIFFERENT STRUCTURES THAT ARE SEEN UNDER THE CRYO ELECTRON MICRO GRAPH OF THE HIV CAPSID. THIS IS ASSEMBLED AMONG CAPSID TO ENCASE THE GENOME TO PROTECT IT AS IT TRAVELS INTO NUCLEUS. WE GET THESE STATIC STRUCTURES AND WE WANT TO KNOW WHAT THEY DID AND HOW IT HAPPENS. AND THEN THAT CAN DRIVE THE NEXT LEVEL OF ANALYSIS. SO, AS A BACKGROUND, MD SIMULATIONS INVOLVING ATOMS HAVE BEEN USED BY PHYSICAL CHEMIST FOR DECADES AND THIS CHEMICAL REACTION IS A NICE EXAMPLE, I THINK, WE CAN COUNT THE ATOMS AND ALMOST COUNT THE NUMBER OF ATOMIC INTERACTIONS AND THIS IS SIMULATING A SIMPLE CHEMICAL AND THE TIME SCALE IS 200 SECOND AND AS A RESULT, THIS TAKES BILLIONS OF CALCULATIONS PER MILLI SECOND OR PICA SECOND OF TIME SCALES AND SO, AS CAN YOU IMAGINE, THIS SECOND MOVIE, WHICH I HOPE WILL ADVANCE, THIS IS A SIMULATION OF A CYTOPLASM AND THESE ARE NOT MOLECULAR STRUCTURES BUT LOW RESOLUTION, LET'S CALL STRUCTURES OF PROTEIN INTERACTING WITH DIFFERENT MOLECULES IN THE CYTOPLASM AND YOU CAN JUST IMAGINE HOW MUCH MORE CALCULATION YOU NEED TO GET TO THIS LEVEL. THAT'S THE ASPIRATION OF THESE STUDIES IS TO REALLY UNDERSTAND HOW PROTEINS WORK AND HOW THEY INTERACT WITH ONE ANOTHER OVER TIME. SO, THE OTHER THING THAT I THINK IS EXCITING ABOUT THIS MOLECULAR DYNAMICS SIMULATIONS IS WE'VE HAD, AS WE KNOW, MASSIVE ADVANCES IN COMPUTATIONAL SCIENCES. WE CARRY OUR IPHONES, SUPER COMPUTERS AND OUR POCKETS EVERYDAY. I USED A COUPLE OF EXAMPLES THAT HAVE GOTTEN A LOT OF PRESS IN THIS SCIENTIFIC COMMUNITY AND THE FIRST BEING ALPHA FOLD A.I. SO THEY'RE A FIRST TIME WE'VE BEEN DOING TO DO THIS FOR 50 YEARS OR MORE. A COMPUTER CAN ACTUALLY CALCULATE PROTEIN STRUCTURE FROM DNA STRUCTURE, FROM AMINO ACID SEQUENCE, I SHOULD SAY. THE PREDICTED INSTRUCTION TURES ARE NEARLY IDENTICAL WE GET UNDER THE CRYO EMs AND AMAZINGLY THIS CURRENT DATABASE CONTAINS STRUCTURE PREDICTIONS FOR THE HUMAN PROTEMOME. WE'RE STILL ACCUMULATING MASSIVE AMOUNTS OF STRUCTURAL DATA AND THE OTHER SYSTEM IS SIMILAR TO THE ALPHAFOLD. THIS IS PUBLISHED IN SCIENCE ANOTHER APPROACH OF NEURO NETWORK ARTIFICIAL INTELLIGENCE CAN PROVIDE ARCHITECTURES THAT ALSO PREDICT THESE STRUCTURES AND AGAIN, WE WANT TO USE THESE THINGS TO ANIMATE STRUCTURES BUT ALSO TO HELP SOLVE VERY DIFFICULT DATASETS. AND THEN I THROUGH THIS ONE OUT THREW THIS ONE BECAUSE IT MADE THE NEWSPAPER AND RATHER INSPIRING AND THAT IS THAT GOOGLE IS CONTINUING TO MOVE TOWARDS THIS IDEA OF QUANTUM COMPUTING. THEY TAKE PROCESSES A THOUSAND FOLD FASTER THAN WHAT WE HAVE NOW SO WE CAN ALMOST SEE THIS ON THE HORIZON. THIS IS ONE PUBLICATION RECENTLY IN SCIENCE SHOWING THE BASICALLY THE ARCHITECTURE OF A COMPUTER PROGRAM FOR QUANTUM COMPUTING AND THEY'VE ALSO VERY RECENTLY REPORTED THE ACTUAL PHYSICAL CONSTRUCTION OR PHYSICAL MAKING OF WHAT IS CALLED A MEMORY CRYSTAL THAT IS JUST TO KIND OF FUTURE, ALMOST FUTURISTIC IDEA OF WHERE COMPUTING WILL BE IN 10 OR 20 YEARS. SO WHAT IS THE IMPORTANCE OF THIS INITIATIVE, NIH IS INVESTED GREATLY IN STRUCTURAL BIOLOGY AND IN PARTICULAR IN HIV STRUCTURE BIOLOGY SO WE HAVE LARGE NUMBERS OF HIGH RESOLUTION STRUCTURES OF NOT JUST MOLECULES BUT COMPLEX MOLECULAR MACHINES. AND AS I SAID, THAT'S STATIC IMAGES PROVIDED A COMPLETE PICTURE OF THEIR FUNCTION AND SO MD CAN LEDGE THESE STRUCTURES TO PROVIDE REAL-TIME SIMULATIONS OF THESE COMPLEX INTERACTION AND GENERATE HYPOTHESIS TO FIGURE HOW THEY'RE WORKING IN LIFE IN REAL LIFE. SO OUR OPPORTUNITY HERE, AGAIN, EXPONENTIALLY INCREASING COMPUTER SPEEDS, ADVANCING IN IT LOOKS LIKE I FORGOT IN MOLECULAR DYNAMICS AND HAVE PUSHED SIMULATIONS INTO THE MILLI SECOND RANGE. WITH THAT CHEMICAL REACTION IN THE PEEK A SECOND RANGE, WE WANT TO PUSH THESE THINGS ALL THE WAY INTO THE SECOND SO THAT WE KNOW WHAT IS HAPPENING IN REAL LIFE. QUANTUM COMPUTING PROMISES TO PUSH THAT FURTHER AND ADVANCES IN MACHINE LEARNING AND ARTIFICIAL INTELLIGENCE MAY ENABLE MORE USER FRIENDLY IN THESE SIMULATIONS. WE WANT TO STIMULATE INNOVATION AND MOLECULAR DYNAMICS TO BRING IT TO GREATER AMOUNTS, GREATER NUMBERS OF HIV RESEARCHERS. THE OBJECTIVES OF PROGRAM ARE SUPPORT COMPUTATIONAL MODELING OF KEY ASPECTS OF HIV LIFE CYCLE INCLUDING INTERACTIONS WITH POST FACTORS AND THERAPEUTICS AND USING NEW STRUCTURAL DATASETS AND INCENTIVIZE COMPUTER SPECIALIST 0 OTHER FIELDS UNDER SCIENCES AND BIOLOGISTS USE A LOT OF MD BUT THESE MOLECULAR COME FROM CHEMISTRY AND PHYSICS SO WE WISH TO REALLY ATTRACT PEOPLE FROM OUTSIDE HIV AND EVEN OUTSIDE OF THE TRADITIONAL BIOLOGICAL SCIENCES TO COLLABORATE WITH OUR HIV STRUCTURAL VIROLOGISTS, CELL BIOLOGISTS AND IMMUNOLOGISTS TO HELP DRIVE INNOVATION IN MOLECULAR DYNAMICS OF HIV INTERVENTIONS AND WE BRING TOGETHER RESEARCH TEAMS INCLUDING COMPUTATIONAL MODELERS AND THOSE ARE THE P.I.s DRIVING THESE RO1s THAT BRING IN STRUCTURAL AND FUNCTIONAL BIOLOGIST TO HELP VALIDATE AND TEST THE MODELS THAT THEY MAKE AND WE'D LIKE TO DEVELOP COLLABORATIONS FOR THIS FIVE-YEAR FUNDING PERIOD THAT EXTEND PAST OF THE FIVE YEARS AND ESTABLISHED MD AS A STANDARD APPROACH TO THE STRUCTURE BIOLOGY OF HIV. EXAMPLE RESEARCH OBJECTIVES, HIV CAPS INTERACTIONS WITH TRANSPORT MACHINERY. WE'RE INTERESTED IN HOW THEY MOVES THROUGH THE CELL. NEXT GENERATION INTEGRATES TRANSFER INHIBITOR BASED ON THE UP STRAIGHTEN DEVELOP OPEN SO THESE ARE CURRENT TOPICS THAT ARE BEING TOSSED AROUND BY STRUCTURAL BIOLOGISTS, HOW TO MAKE NEXT GENERATION DRUGS. HIV ASSEMBLY AND ESCRT-MEDIATED BUDING AND RELEASE AND HIV ENV-MEDIATED RECEPTORS BINDING AND FUSION AND BINDING OF HIV ANTI-AGAINST TO B-CELL SURFACE. IT'S NOT HIV ONLY BUT HIV RELEVANT. THINGS RELEVANT TO PREVENTION THERAPY AND CURE AND FINALLY HIV RECOGNITION AND ESCAPE FROM INNATE IMMUNE FACTORS. SO, WE ARE NOT SUPPORTING THIS INITIATIVE, WE WANT TO APPLICATION THAT'S FOCUS PRIMARILY ON -- NOT SUPPORTED IS APPLICATION THAT'S DON'T FOCUS PRIMARILY ON DYNAMIC MODELING OF HIV HOST STRUCTURAL DATA RELEVANT TO THESE KEY PROPERTIES. APPLICATIONS THAT ONLY INVOLVE THEE RECEIPT CAL MODELING WITHOUT A SET OF KNOWN MOLECULAR SET OF STARTING POINTS. WE WANT A PHYSICAL STATIC IMAGE GENERATED BY EXISTING OR PROPOSED STRUCTURAL BIOLOGISTS. STRUCTURAL SOLVED STRUCTURES. AND WE WILL NOT ALSO APPLICATION THAT'S DO NOT INCLUDE FUNCTIONAL ANALYSIS. WE WANT IT TO NOT JUST BE A MODELING INITIATIVE BUT MODELING IN HYPOTHESIS AND THEN TEST TO THE HYPOTHESIS BY THE VIROLOGIST AND STRUCTURAL BIOLOGISTS. RELATIONSHIP TO OTHER AWARDS OR PROGRAMS, SO THE CENTER FOR HIV STRUCTURE BIOLOGY IS OUR CENTER PIECE IN THE BASIC SIGNS PROGRAM AND IT SUPPORTS CURRENTLY FIVE CENTERS. THEY REALLY ARE FOCUSED ON GENERATING HIGHLY COMPLEX HIV STRUCTURES THAT HAVE SPRINKLES ALL THE WAY UP THROUGH HERE SO AGAIN MULTI-MOLECULAR STRUCTURES THAT ARE INTERACTING WITH HOST FACTORS. THEY'RE ENCOURAGED TO LEVERAGE COMPUTATIONAL TECHNOLOGIES, OF COURSE, AND THE RELATIONSHIP HERE IS THAT ONLY A SMALL SUB AWARD HAVE TRADITIONALLY GONE TO MD SPECIALISTS FOR STRUCTURAL DATA. THEY USE COMPUTATIONAL TECHNOLOGIES TOGETHER TO PUT TOGETHER THE MODEL OF THE STRUCTURE BUT THEY DON'T ALWAYS USE MD TO MOVE THOSE MODELS INTO SPACE AND TIME AND IMPORTANTLY THE REASON THAT WE IDENTIFIED THIS GAP IS THAT DAIDS SUPPORTS FEW COMPUTATIONAL BIOLOGIST WITH INDEPENDENT FUNDING, I'VE ONLY IDENTIFIED ONE SPECIFICALLY RO1 WITH MD SPECIALIST WITH THEIR OWN GRANT. WE WISH TO EXPAND THAT. SO, THE REVIEWERS WERE Dr. HARRIS AND AROL AND THANK YOU FOR THEIR REVIEW. THEY'RE VERY SUPPORTIVE OF THIS INITIATIVE AND HAD THE FOLLOWING SUGGESTIONS AND RECOMMENDATIONS. THEY RECOMMEND THAT MORE EMPHASIS BE ON ATTRACTING MD SPECIALISTS FROM NON HIV BIOMEDICAL SPECIALITIES. I CHANGED MY SLIDES TO REFLECTS THAT. OF COURSE, WE WOULD LIKE TO BRING THESE PEOPLE IN FROM WHERE THEIR SPECIALITIES BRINGS AND A TRACATTRACT THEM TO HIV BIOLOGY AND KEEP THEM HERE. WE ENCOURAGE INNOVATION. WE SHOULD CLARIFY WHETHER MD STUDIES WILL UTILIZE EXISTING DATASETS OR COLLECTION OF NEW DATA STRUCTURE WILL BE ALLOWED AND WE'RE ALLOWING EXISTING DATASETS BECAUSE WE HAVE A LARGE CATALOG AND NEW STRUCTURAL DATA AND HYPOTHESIS TESTING STRUCTURE BIOLOGY. REVIEWERS ALSO RECOMMENDED LIMITING THE SCOPE TO STRUCTURES THAT HAVE DIRECTING INTERACT WITH HIV PROTEINS OR DIRECT INVOLVEMENT IN HIV REPLICATION. WE DO GROW WITH THESE RECOMMENDATIONS. WE RECOMMENDED EXPLORING POTENTIAL INTERACTIONS WITH THE NATIONAL LIBRARY OF MEDICINE AND NSF AND THIS WOOS A CONVERSATION THAT OPENED MY EYES TO THE NSF TRANS AGENCY PROGRAM CALLED SMART AND CONNECTED HEALTH. OBVIOUSLY, WE HAVE A LOT OF INTEREST IN COMPUTER POWER, COMPUTER PROCESSING, AND NSF OF COURSE IS REALLY DRIVING A LOT OF OUR COMPUTATIONAL SCIENCES. WE NOTE THAT THE NIH ADVISORY COMMITTEE RECOMMENDED A COMMON FUNDED INITIATIVES TO ADVANCE ARTIFICIAL INTELLIGENCE OVER THE NEXT SEVEN YEARS OF OVER $160 MILLION. LARGE INVESTMENT BY NIH FOR THESE KIND OF COMPUTATIONAL BIOLOGY. AND THEN FINALLY, THE QUESTION WAS, HOW IS THE 3 MILLION-DOLLAR ANNUAL COST FOR THE INITIATIVE ARRIVED AT AND IS IT ENOUGH? SO, WE THINK WHEN WE DEVELOP THIS INITIATIVE, WE HOPED TO BRING IN THREE OR FIVE MD SPECIALIST TO SUPPORT THREE TO FIVE AWARDS. WE WOULD AGREE THAT IF WE CAN IDENTIFY ADDITIONAL MERITORIOUS APPLICATIONS WE'LL WORK WITH OUR BUDGET TEAM TO APPROVE THAT TO INCREASE THAT NUMBER. AND THAT IS MY PRESENTATION. THANK YOU FOR YOUR ATTENTION. I'LL TAKE ANY QUESTIONS. >> GREAT. THANK YOU Dr. MACDONALD. REALLY EXCITING INITIATIVE. VERY EXCITING. QUESTIONS FROM THE COMMITTEE? >> I'M JUST THE POINT THEY ALREADY MADE THAT BOTH RUBEN AND I WERE VERY EXCITED ABOUT THIS INITIATIVE. WE THINK IT'S TERRIFIC. >> THANK YOU I ENJOYED THAT CONVERSATION AND IT WAS VERY USEFUL. THERE'S ALBERTA OF ENTHUSIASM HERE. THANK YOU FOR THE PRESENTATION. BEST MOVIES I'VE SEEN TODAY FOR SURE. >> WE HAVE BETTER ONES. >> THE SEQUEL ARE NEVER AS GOOD AS THE ORIGINAL. IF EVERYONE CAN VOTE ON THAT. THANK YOU AGAIN. MAKE SURE YOU REGISTER YOUR VOTE. SOMETHING I ALWAYS FORGET TO DO. OK, WE'LL NOW HAVE A BREAK, ACTUALLY. WE'RE RUNNING EARLY BY NINE MINUTES SO WE HAVE A 10-MINUTE BREAK AND WE'LL RECONVENE AT WHATEVER THAT WILL BE. 2:21. SO, WE'LL BE BACK IN 10 MINUTES. >> WELCOME BACK, EVERYONE. WE HAVE TWO MORE PRESENTATIONS THIS AFTERNOON AND THE FIRST IS FROM Dr. GERALD SHARP. LIMITED INTERACTION TARGETED EPIDEMIOLOGY, AND VIRAL SUPPRESSION AND LITE-VS. >> THANK YOU, KEN. LIMITED ACTION TARGETED EPIDEMIOLOGY ARE LIGHT IS WHAT WE USED IN A PREVIOUSLY TO LOOK AT PREVENTION OF HIV AND WE USE SOCIAL MEDIA TO TARGET HIGH-RISK PEOPLE WHO WERE NEGATIVE FOR HIV AND IT WAS A WAY TO ENROLL THEM IN LARGE STUDIES AND TO TRY TO FIND WAYS TO PREVENT HIV. THE IDEA NOW IS TO USE THE SAME TECHNOLOGY OF USING SOCIAL MEDIA TO REACH PEOPLE TO FIND PEOPLE WHO HAVE HIV AND LIVING WITH HIV AND FIND WAYS TO HELP THEM TO BE VIRALLY SUPPRESSED. SO THE PURPOSE IS TO DEFINE INDIVIDUAL CONTEXTUAL RISK FACTORS AND PEOPLE LIVING WITH HIV THAT ARE ASSOCIATED WITH INADEQUATE BIO SUPPRESSION ZOOSING METHODS THAT MAXIMIZE OUTREACH TO UNSUPPRESSED PEOPLE LIVING WITH NIH AND TO USE THE FINDINGS TO DESIGN AND CONDUCT PRIVATE STUDIES TO IMPROVE OUR SUPPRESSION AND OTHER STUDY OUTCOMES AND IT'S IMPORTANT BECAUSE SUPPRESSION OF HIV AMONG PEOPLE WITH HIV IN THE UNITED STATES IS ESSENTIAL FOR PATIENT CARE AND INTERVENTION OF HIV TRANSMISSION AND DESPITE ADVANCES IN METHODS, IT REMAINS A CRITICAL PROBLEM IN THIS COUNTRY. THE MECHANISM THAT WAS ALSO USED IN THE OTHER ORIGINAL LIGHT FOR PREVENTION IS THIS EG3, UH3 MILD STAGE DRIVEN RFA IN A CLINICAL TRIAL OPTIONAL. THE WAY IS WORKS IS THERE'S A TWO YEAR INITIAL PHASE AND IF THEY'RE SUCCESSFUL MEETING WHERE NO-GOAL TARGETS, THEY GET THREE YEARS OF FUNDING. IT LET'S PEOPLE DO RISKY THINGS IN ORDER TO ACCUMULATE THEIR TARGETS AND THEIR PARTICIPANTS BUT IT ALSO ALLOWS TO US TO CUT OFF FUNDING. FIRST YEAR COST IS $3 MILLION FROM THE NIAID COMMITMENT AND NIH HAVE AGREED TO CO FUND THIS AND NIMH AN AND HAD THE LIGHT FOR PREVENTION AND WE HOPE THAT NICHD WILL COME IN ON THIS. IT'S NOT JUST THE MONEY BUT HAVING PARTICIPATION FROM THESE OTHER INSTITUTES WITH THEIR EXPERTISE THAT REALLY HAVE HELPED LIT TO BE AS SUCCESSFUL AS IT'S BEEN. THIS IS JUST A LITTLE BACKGROUND ON THE EPIDEMIOLOGY OF THE VIRAL SUPPRESSION IN THE UNITED STATES. THE CDC AND YOU CAN SEE ON THAT MAP ON THE LEFT, COLLECTS BIO SUPPRESSION DATA FROM 41 STATES IN THE DIRECTING OF COLOMBIA IN BLUE AND THE RED IS COLORED STATES DO REPORT AND THE INCOMPLETE STATES FOR YELLOW. IN THIS CASE, I THINK THE MEASUREMENTS HERE ARE GOING TO BE SOMEWHAT OPTIMISTIC IN THAT COVID HAS HAD A DRAMATIC EFFECT ON HIV AND TESTING, AND ON VIRAL SUPPRESSION OF HIV IN THIS COUNTRY AND SO I THINK ABOUT WHAT WE'RE SEEING HERE MAY BE BETTER THAN WHAT WE ACTUALLY HAVE TODAY. THE DENOMINATOR IS PERSONS AGED 13 YEARS AND OLDER WITH HIV DIAGNOSISSED BY THE END OF 2017 WHO ARE A LIVE AT THE END OF 2018. CDC DEFINES VIRAL SUPPRESSION AS A VIRAL LOAD OF LESS THAN 200 COPIES UNDER MOST RECENT VIRAL LOAD TEST AND THIS IS OVER ESTIMATE BECAUSE IT IGNORES UNDIAGNOSED PERSONS LIVING WITH HIV AND ALSO IGNORES PEOPLE WHO ARE NOT IN CARE AS WELL AS PEOPLE WITH HIV WHO MAY NOT BE SUPPRESSED FOR THE FULL YEAR SINCE IT'S BASED ON THE MOST RECENT VIRAL LOAD MEASUREMENT AND ON THE RIGHT SIDE HERE, I'VE SHOWN THE DATA FROM CDC ON VIRAL SUPPRESSION BY GENDER AND IT'S LOWER FOR FEMALES AND MALES 63% WERE 65% OF MEN. HIGHER FOR TRANSGENDER MALES AT 71.5% AND OTHER GENDERS. THIS OTHER CATEGORY HERE ON THE RIGHT. BUT THE NUMBERS ARE LIMITED FOR THOSE TWO GROUPS. SUPPRESSION INCREASES WITH AGE. FROM 60.5% FOR AGES 13-34 TO A HIGHER LEVEL OF 66% FOR THOSE AGE 45 AND OLDER. IN TERMS OF OTHER FACTORS, RACE IS IMPORTANT. YOU CAN SEE HERE ON THE LEFT, THE SUPPRESSION RATES BY STATE. THEIR RATES ARE LOWER IN THE SOUTH AND THE OTHER STATES MARKED IN DARK BROWN AND ALSO THE STATES THAT ARE DARKER COLORS, BY RACE, OVER ALL, ABOUT TWO-THIRDS OF PEOPLE WERE SUPPRESSED. THE WHITE RATE WAS BEEN 70.7% AND LATINO RATE 63% AND THE BLACK RATE DECLINED TO JUST UNDER 60%. BASED ON, AGAIN, ON THE SINGLE MOST RECENT VIRAL LOAD AND SOMEONE HAS A STUDY TO COMPARE THE SINGLE MEASUREMENTS TO PEOPLE WHO WERE SUPPRESSED BY THEIR WHOLE YEARLY LEVELS AND IT LOOKS LIKE THE SUSTAINED VIRAL SUPPRESSION WHICH MEANS SUPPRESSED FOR THE ENTIRE TIME IS 16% LOWER THAN THESE NUMBERS HERE THAT I'M GIVING YOU. WHICH ARE BASED ON THAT INDIVIDUAL MEASUREMENT. 70% OF THE 1.2 MILLION PEOPLE LIVING WITH HIV IN THE UNITED STATES, ARE RACIAL ETHNIC MINORITIES SO IT'S ESSENTIAL TO IMPROVE VIRAL SUPPRESSION IN THESE GROUPS. CDC ALSO DID THIS REALLY INTERESTING STUDY THAT LOOKED AT 13 TO 29-YEAR-OLDS IN THEIR CATCHMENT AREA. THE 41 STATES IN THE DISTRICT OF COLOMBIA AND THEY HAD A HUGE NUMBER SHY OF 91,000 PEOPLE IN THIS STUDY AND THEY POINT OUT THAT THIS AGE GROUP IS COMPRISING OF 23% OF THE U.S. POPULATION BUT IT ACCOUNTS FOR 42% OF THE ANNUAL HIV INFECTION ZOOS IT'S SSO IT'S AN IMPORTANT POPULATION TO DEAL WITH. OF THE 90 HOW PEOPLE LIVING WITH DIAGNOSED HIV, 41% WERE UNDETECTABLE FOR ALL THE REST DURING ONE YEAR AND AGAIN AS I SAID BEFORE, IT'S ABOUT 16% LOWER THAN THOSE MEASUREMENTS BASED ON A SINGLE VIRAL LOAD. AGAIN, THERE WERE DISPARITIES BY RACE, ABOUT A THIRD OF BLACKS IN A STUDY WERE UNDETECTABLE FOR ALL THEIR TESTS, LATINO, LATINA, A LITTLE HIGHER AT 46.7% AND WHITES IT WAS JUST SHY OF 51%. AGAIN, DISPARITIES BY INDIVIDUAL CHARACTERISTICS, MSM SHOWED A VIRAL LOAD OF -- VIRUS SUPPRESSION LEVELS OF 44.7% AND AS THIS NORMAL, PEOPLE WHO INJECT DRUGS HAVE LOWER LEVELS. 30-POINT 9% PER MALE AND 32.0% FOR FEMALES AND SO THEN WHAT THESE INVESTIGATORS DID IS THEY LOOKED AT THESE PEOPLE WHO WERE NOT SUPPRESSED FOR THE ENTIRE YEAR AND JUST LOOKED AT WHAT THEIR VIRAL LOADS WERE FOR THOSE TIMES WHEN THEY WERE NOT SUPPRESSED. AND OF THE 28,000 WHO FELL INTO THOSE CATEGORIES, OF NOT BEING CONSISTENTLY UNDETECTABLE, THEY MEASURED THE DAYS OF YEAR WHICH THEIR VIRAL LOADS WERE IN EXCESS OF 1500 PER MILL LITER AND IT'S AN IMPORTANT LEVEL BECAUSE IT'S THE POINT WHERE WE BELIEVE THAT HIV BECOMES TRANSMISSIBLE. SO, THE AVERAGE WAS 206 OF THOSE DAYS AMONG THIS GROUP WHERE THEY HAD VIRAL LOADS THAT WERE NOT ONLY BAD FOR THEM BUT ALSO MAKES THEM POSSIBLE ABLE TO INFECT OTHERS. AND AGAIN, AS WE'VE SEEN BEFORE, A LOT OF DISPARITIES BY RACE, WHITES WERE A LOT THESE HIGH LEVELS FOR ABOUT HALF OF THE YEAR. LATINO, LATINA FOR 198 DAYS OR 54% OF THE YEAR AND BLACK FOR 213 DAYS OR 58% OF THE YEAR. SO IT'S EDG ESSENTIAL TO PROVIDE AMONG PEOPLE WHERE THE VIRAL LOADS ARE HIGH ENOUGH THEY CAN ACTUALLY TRANSMIT THE VIRUS. SO, IN TERMS OF WHAT WE'VE DONE IN LIGHT WITH THE PREVENTION STUDIES, WE USED THESE DIGITAL APPROACHES TO STUDY IN THE U.S. EPIDEMIC AND WE FEEL THE SAME TECHNIQUES THAT WE DEVELOPED TO LOOK AT PREVENTION CAN BE USED NOW TO LOOK AT VIRUS SUPPRESSION SO WE USED SOCIAL MEDIA, WE USED THE DATAING APPS, Facebook, SNAP CHAT AND WHATEVER AND BY DOING THIS, THE MAP HERE ON THE RIGHT IS CHRISTIAN GROVES PARTICIPANTS STUDY AND HE ENROLLED PARTICIPANTS THROUGHOUT THE UNITED STATES AND ALSO IN PUERTO RICO AND GUAM. AND WHAT THIS DOES IS BY HAVING THIS ABILITY TO USE SOCIAL MEDIA TO REACH PEOPLE, THERE'S NO LIMITS ON ENROLLMENT. YOU CAN HAVE ANY LOCATION, ANY PARTICIPANT CHARACTERISTICS, RURAL OR AR BAN AND ALL GENDERS AND AGES AND THE OTHER THING THAT'S AN ADVANTAGE, I MEAN, I'VE SHOWN YOU DATA FROM CDC THAT IS THREE-YEARS-OLD, THIS ALMOST WORKS IN REAL-TIME BECAUSE THEY CAN CONTACT THE PARTICIPANTS USING THE INTERNET OR USING TEXTING AND GET A IMMEDIATE RESEARCH DONE ON WHAT IS CHANGING IN TERMS BEFORE IT WAS PREVENTION AND NOW IT WILL BE CHANGES IN VIRAL SUPPRESSION AND AS I SAID, THEY ENROLL PARTICIPANTS IN ALL 50 STATES, OVE50 STATES.OVER ALL THE STUDIES FUNDED UNDER LIGHT SCREENED 140,000MSN AND TRANS GENDER PERSONS THROUGHOUT THE UNITED STATES AND THE TERRITORIES. AND THE HIGHEST RISK PARTICIPANTS WERE MALE HIV TEST KITS AND ENROLLED AND AS OF THOUSAND ABOUT 20,000 ARE STILL UNDER FOLLOW-UP. THERE'S OPTIONS FOR MEASURING ARV USE AND VIRAL LOAD MONITORING THAT WORKED IN THE HOME. MAYBE USING LABS OR LOCAL PHARMACIES. ALSO, WE ARE ABLE TO USE SELF-TESTING FOR ARB EXPOS YOU'RE AND VIRAL AND THESE TESTS ARE COMING TO MARKET AND THERE'S A URINE TEST AVAILABLE AND INEXPENSIVE AND ALSO HOME BASED DRY BLOOD SPOT TESTING IS A VARIABLE AND VIRAL LOAD TESTING IS IN DEVELOPMENT AS WELL AS USING DIFFERENT PHARMACY TESTS OR WHATEVER AND LIGHT TO MEASURE PEOPLE WHO BECAME HIV INFECTED THEY ARE ABLE TO USE THEIR LOCAL CLINICS AND THEN SEND IN JUST A PAPER THAT SHOWS WHAT THE RESULTS WERE AND ANY RATE, THESE SAME TYPE OF REMOTE METHODS THAT WERE USED IN LIGHT FOR THE PREVENTION WORK, CAN ALSO BE USED TO ENROLL AND FOLLOW PEOPLE LIVING WITH HIV IN THE UNITED STATES. SO THE PROGRAM GOALS FOR LITE VIRAL SUPPRESSION TO ENROLL LARGE, GREATER THAN 1,000 MEMBERS OF PARTICIPANTS. LESS INTENSIVELY FOLLOWED COHORTS OF HIV-POSITIVE MEN AND WOMEN IN THE UNITED STATES, TO DEMONSTRATE THE COHORT SIZE THEY CHOSE IS ADEQUATE STATISTICALLY AND THEY CAN RETAIN THEIR PARTICIPANTS. THIS IS AN EMPHASIS ON BLACK AND LATINA AND LATINO GROUPS WHERE THE VIRAL SUPPRESSION RATES ARE LOWER AND THERE'S A HIGH PREFERENCE OF HIV. THE RFA REQUIRES AT LEAST 50% OF THE PARTICIPANTS IN STUDIES FUNDED BY THIS RFA HAD MINORITY STATUS AND THIS WAS ALSO DONE IN THE PREVENTION STUDIES WHERE IT TURNED OUT TO BE AN IMPORTANT FACTOR BECAUSE IT FORCED INVESTIGATORS TO ENROLL THESE MUCH MORE DIFFICULT TO ENROLL PARTICIPANTS. ALSO THERE'S AN EMPHASIS ON MEN AND WOMEN, PERSONS AGE 13-44 YEARS AND PEOPLE LIVING IN THE SOUTH AND STATES WITH THE LOWEST VIRAL SUPPRESSION LEVELS. THE IDEA IS TO DEVELOP INNOVATIVE, PRIMARILY ELECTRONIC METHODS OF ENROLLMENT AND FOLLOW-UP TO DEVELOP REMOTE MEASURES OF ARB ADHERENCE AND VIRAL SUPPRESSION AND AT HOME TEST VEIL AND REFERRAL TO LOCAL LABS, CLINICS, BLOOD SPOT TESTING AND COMPARE PARTICIPANTS WHO MAINTAIN VIRAL SUPPRESSION TO THOSE WHO DON'T TO DEFINE INDIVIDUAL AND CONTEXTUAL RISK OF NON ADHERENCE OR LACK OF VIRAL SUPPRESSION AND DEVELOP NON-BASED OF U.S. PEOPLE LIVING WITH HIV WHO ARE LESS LIKELY TO BE SUPPRESSED. AGAIN. THE EMPHASIS IS ON PEOPLE LIVING WITH HIV WHOSE VIRAL LOADS EXCEED 1500 COPIES PER MILLILITRE. IT'S AN OPTION TO CONDUCT CLINICAL TRIALS BUT IF THEY WISH TO, THEY CAN CONDUCT PILOT STUDY OF DIGITAL TILES TO IMPROVE SUPPRESSION IN OTHER STUDY OUTCOMES. THE MAJOR GOAL IS TO PROVIDE INFORMATION AND PILOT DATA NEEDED TO DEVELOP LOW COST, SCALABLE PROGRAMS, TO IMPROVE VIRAL SUPPRESSION UNTIL THE UNITED STATES. IT'S A MILESTONE DRIVEN PROCESS. INITIAL THE RIGHT OF GRANT APPLICATION WITH OR WITHOUT THE CLINICAL TRIAL OPTION AND THE INVESTIGATORS WILL SET PEOPLE LIVING WITH HIV ENROLLMENT TARGETS INCLUDING GOALS BY AGE AND MINORITY STATUS AND ASSESSING ADEQUATE NUMBERS OF NON SUPPRESSED PARTICIPANTS AND THEY HAVE TO OUTLINE THEIR PLANS FOR RESEARCH COMPARING THE SUPPRESSED AND NOT SUPPRESSED PARTICIPANTS AND PHASE 1 THE INVESTIGATORS WILL DEMONSTRATE SUCCESS AND MEETING THE ENROLLMENT AND OTHER MILESTONE GOALS AND IF THEY FAIL, THE GRANTS WILL BE CLOSED OUT AT YEAR THREE. IF THEY SUCCEED IN MEETING THEIR TARGETS, UNDERSTAND PHASE YEARS THREE TO FIVE THEY'LL CONDUCT RESEARCH FOR EXAMPLE, THEY'LL COMPARE SUPPRESSED AND NON SUPPRESSED PARTICIPANTS, CONDUCT PILOT TRIALS TO IMPROVE BIO SUPPRESSION USING DIGITAL INTERSECTION THAT'S CONSIDERED GEOGRAPHIC AND PARTICIPANT CHARACTERISTICS AND ARE RELATIVELY LOW COST IN SCALABLE. THEY MAY USE E-HEALTH METHODS FOR PATIENT REMINDERS, FOR EXAMPLE, FACE TIME, TENSIONING, E-MAIL, PHONE CAPS, THEY MIGHT USE PHARMACY AIDS OR REFILL SUPPORT PROGRAMS AND THE GRANTS WILL NOT PAY FOR ARVs BUT THE INVESTIGATORS CAN ASSIST PARTICIPANTS IN OBTAINING ARVs. THE SECOND PHASE MAY INCLUDE INTERVENTIONS AND I'M NOT GOING TO GO THROUGH ALL THESE POSSIBLE INTERVENTIONS HERE BUT IT'S MESSAGING BOARDS AND TRAIN COUNSELING AND THIS BEHAVIORAL CHANGE WHERE MONITORING RECENT SEXUAL BEHAVIOR WITH MESSAGING AND LINKAGE TO CARE AND HIV CARE WHERE MAYBE IT WOULD BE A SMARTPHONE APP TO IDENTIFY LOCAL RESOURCES AND CULTURALLY APPROPRIATE HIV CARE FOR AFRICAN AMERICAN MSM AND ALSO CARE SUPPORT MAYBE A WESTBOUND BASED SELF-CARE PROGRAM TO ADDRESS PSYCHO SOCIAL IMPACT OF HIV OR SELF-CARE APP FOR ADHERENCE, MENTAL HEALTH IS SCHEDULED APPOINTMENTS. FOR THIS, THE GOAL BEEN BE QUALITY OF LIFE FOR PEOPLE WITH HIV. IT'S GOING TO BE HOW CAN WE HELP PEOPLE TO BE SUPPRESSED FROM THE VIRUS? WE HAVE MY REVIEWERS, THEY BOBBLBOTHSUPPORTED THIS NEW. IS SELF-COLLECTION FEASIBLE FOR FEASIBLE FOR PARTICIPANTS IN NEED STUDIES. I REACHED OUT TO DENNIS NASH USING A SELF-COLLECTED DBS SPECIMEN COLLECTION KIT WITHIN AN INSTRUCTIONAL VIDEO AND ACTUALLY FOR DRYING THE BLOOD. THE PARTICIPANTS ARE REQUESTED TO MAIL DRY BLOOD SPOT CARTS TO THE STUDY LAB FOR ZERO LOGIC TESTING AND 4500 OUT OF 6753 OR 67% WERE TESTED ONCE AND OF THOSE 80% WERE TESTED TWICE AND THAT SELF-COLLECTION OF DRIED BLOOD SPOTS IS FEASIBLE AND LIKELY TO BE FEASIBLE TO MEASURE THE VIRAL SUPPRESSION AND Dr. GANDHI SAID THIS IS VERY HIGH-IMPACT AND THESE ARE THE PATIENTS WE NEED TO REACH AND EVERYONE IS ON SOME SORT OF SOCIAL MEDIA OR APP. EVEN IF THEY DON'T COME TO CLINIC AND WE AGREE THAT USING SOCIAL MEDIA IS A FEASIBLE AND EFFICIENT WAY TO REACH PEOPLE LIVING WITH HIV OUTSIDE THE CONTEXT OF CLINICS. Dr. FREEDBERG, GIVEN HIGH RATES OF STUDY WITH PEOPLE AS IN 1,000 BE VALUABLE AND ALLOW MORE PROPOSALS TO BE FIND AND OUR PHONES WAS THE LITE STUDIES REQUIRED 5,000 OR MORE FOR PANTS BECAUSE HIV-SEROCONVERSION IS RARE 1.1% TO 3% AND I'VE SHOWN YOU THE NUMBER FOR VIRAL LOAD SUPPRESSION WHICH AS YOU CAN SEE ARE MUCH. WE AGREE THAT WE MAY BE ABLE TO USE SMALLER SAMPLE SIZES WHILE STILL ENSURING SUFFICIENT STATISTICAL POWER AND ORIGINALLY, WE HAD REQUIRED SIZE WAS 2,000 AND WE ACTUALLY DROPPED IT TO 1,000 BASED ON Dr. FREEDBERG'S COMMENT. LET'S TAKE YOU BACK TO MY ORIGINAL SLIDE THAT SUMMARIZES THE RFA. >> GREAT, THANK YOU Dr. SHARP. QUESTIONS OR COMMENTS FROM THE COMMITTEE? YES. >> THIS IS GREAT. I CONCUR WITH THE REVIEWERS FOR SURE. IF YOU -- BECAUSE YOU HAVE THE WORD CONTEXT THERE YOU ARE THINKING ABOUT THE STRUCTURAL BARRIERS AND I'M THINKING OF HOMELESSNESS AND I SAW MENTAL HEALTH AND SUBSTANCE USE BUT I'M WONDERING, I THINK THIS IS A GREAT WAY TO REACH PEOPLE WHO AREN'T COMMITTED CLINIC BUT STILL THINK ABOUT THE MOST MARGINALIZED AND SOME OF THESE PLACES AND SOME OF THE STRUCTURAL BARRIERS THAT FOLKS ARE FACING AND HOW YOU ANTICIPATE ADDRESSING THINGS LIKE POVERTY AND PEOPLE WHO ARE ON THE OUTSKIRTS OF A LITTLE BIT MORE WITH THIS. >> IT'S UP TO THE INVESTIGATORS. SURELY STRUCTURAL FACTORS ARE IMPORTANT. THEY MIGHT WANT TO PAY FOR PEOPLE'S TO GET TO THE CLINIC. I HADN'T THOUGHT ABOUT THIS BEFORE, IT WASN'T LISTED ON MY TARGET GROUP, THE BUT THE HOMELESS. WE WANT TO INCLUDE THEM AS A TARGET. MONICA, EARLIER WHEN WE WERE TALKING ABOUT ONLY 20% OF THE HOMELESS POPULATION ARE SUPPRESSED? THAT'S A HUGE PROBLEM. I THINK I WANT TO ADD THAT. >> USING DATA FROM SAN FRANCISCO, YEAH. WHICH IS REALLY DISTURBING BECAUSE THIS WAS IN THE CONTEXT OF COVID AND IT DROPPED QUITE A BIT. >> I THINK MAYBE, I DON'T KNOW EXACTLY HOW PEOPLE WOULD USE SOCIAL MEDIA TO REACH THEM BUT MAYBE IT'S WORTH A TRY. IT'S A REALLY IMPORTANT GROUP. THE STRUCTURAL FACTORS CAN BE VERY, VERY IMPORTANT AND IT'S UP TO THE INVESTIGATORS TO FIGURE OUT HOW TO DEAL WITH THAT. I THINK IT'S POSSIBLE. >> GERALD ALSO COMMENT FROM Dr. KIM SMITH, SUPPORTIVE OF THIS IMPORTANT INITIATIVE AND STATISTICS ARE TERRIBLE IN PERIODS OF COLOR AND FIVE TO SIX AWARDS ARE NOT ENOUGH. DO YOU COMMENT ON THAT? >> I AGREE. [LAUGHTER] >> I TOTALLY AGREE WITH THAT. >> I MEAN, YOU KNOW, I'M PREPARING THIS, WE'VE HAD THE DRUGS TO TREAT HIV FOR 25 YEARS. WE HAVE 35,000 CASES A YEAR. LET'S FIX IT. LET'S DO SOMETHING. SOCIAL MEDIA IS AN IMPORTANT THING. LET'S USE IT TO REACH THESE PEOPLE. WE'VE TRIED CLINICS. LET'S TRY THIS OTHER APPROACH. SO, YEAH, I TOTALLY GROW AND IT'S REALLY IMPORTANT. >> JUST TO ADD, YOU KNOW, OBVIOUSLY I HAVE A BUY A I HAVE A BIAS HER E. WE HAVE A NEW TOOL IN LONG-ACTING THERAPY WE'VE NEVER HAD BEFORE. IT CAN BE USED, AT LEAST STUDIED STUDIED, AND IN AN AGGRESSIVE FASHION THAT CARES FOR HOMELESS, THERE'S SO MANY -- THIS IS A TOOL THAT CAN BE USED IN A CREATIVE WAY TO GET TO POPULATIONS AND YOU I ABSOLUTELY BELIEVE, WE ALL BELIEVE IN COMMUNITIES THAT ARE POOR AND THAT THE NOTION OF VIRTUAL VISITS IF YOU DON'T HAVE INTERNET, IS NOT REALISTIC. SO I JUST DO FEEL LIKE THIS IS AN IMPORTANT INITIATIVE AND IT NEEDS TO BE AMPED UP AND PARTNERSHIPS ARE CRITICAL. >> I AGREE. I MEAN, I THINK IT'S AN INTERESTING TIME WITH THE ADVENT OF THE INJECTABLES THAT THIS IS COMING ON BOARD. IT WOULD BE INTERESTING TO SEE HOW THE GRANTEES WILL INCORPORATE THAT. IT'S A GREAT IDEA. I AGREE. >> COUPLE MORE QUESTIONS FROM THE CHAT AND THEN I SEE YOUR HAND, IAN AS WELL. THERE ALSO ANOTHER CRITICAL STRUCTURAL FACTOR FOR A STUDY LIKE THIS AS JUST MENTIONED. THE DIGITAL DIVIDE STILL PERSISTS AND SHARPLY SO AMONG MARGINALIZED POPULATIONS. SHALL YOU SPEAK TO THAT. >> I MEAN, I THINK PEOPLE HAVE PHONES. I KNOW YOU MAYBE HOMELESS BUT I THINK YOU STILL HAVE A PHONE BECAUSE IT'S JUST BECOME SUCH A HIGH PRIORITY THAT TO PLUG INTO SOCIETY AT ALL. I MEAN, OK, IF THEY DON'T, THEN THEY'RE NOT GOING TO BE INVOLVED IN THESE STUDIES BUT I THINK WE'RE GOING TO REACH A LOT OF PEOPLE THROUGH PHONES. >> IT MAY BE THAT FOR THE LIMITED NUMBER OF PEOPLE WITHOUT PHONES, IT MAY BE THAT IT COULD BE PUT IN THE BUDGET IN SOME FASHION. IT'S IMPORTANT. STEPHAN, DO YOU WANT TO SAY YOUR COMMENT RATHER THAN ME READ THEM AND I SEE IAN, RICH AND ANITA. >> I JUST WANTED TO COMMENT THAT I AGREE WITH MY COLLEAGUES, Dr. SMITH, THAT FIVE TO SIX AWARDS SEEMS VERY LIMITED AND THERE'S A HUGE NEED TO ADDRESS THE CARE CONTINUUM IN THIS COUNTRY, PARTICULARLY AMONG PEOPLE WHO ARE ECONOMICALLY DISADVANTAGED AS WELL AS THE RURAL SOUTH. I CONTINUE TO SEE TRANSGENDER COMMUNITIES OVERLOOKED IN TERMS OF THE DATA IN THAT THERE'S NOT ENOUGH BEING DONE TO ENSURE THAT WE'RE COLLECTING DATA IN THESE POPULATIONS. PARTICULARLY TRANSGENDER COMMUNITIES OF COLOR. >> I WAS SURPRISED WITH THE LITE STUDIES, THE PREVENTION STUDIES, THEY WERE ABLE TO REACH VERY MANY TRANSGENDER WOMEN AND SUBSTANTIAL NUMBER OF TRANSGENDER MEN. MOSTLY USING THE SEX APPS SO YEAH, THEY'RE REACHABLE THROUGH THIS INITIATIVE AND ALSO THOSE WHO HAVE BEEN INFECTED WITH HIV. ALSO MINORITIES, YEAH, I AGREE. >> QUESTION Dr. FRANK. >> THANK YOU, KEN. SO, YOU KNOW, I THINK THAT THE PEOPLE WITH HIV ARE GOING TO BE DIFFERENT THAN THE PEOPLE WHO WERE ATTRACTED TO THE LITE INITIATIVE WHO NEED HIV PREVENTION SERVICES AND ALTHOUGH I'M NOT ARGUING AGAINST THIS INITIATIVE, I THINK THAT IN SOME WAYS WE NEED THE OPPOSITE OF THIS FOR MANY PEOPLE WHO AREN'T SUPPRESSED, WHICH IS SOMETHING MORE INTENSIVE THAT OUR CLINICAL SERVICES CANNOT PROVIDE. IN PHILADELPHIA, WE HAVE HAD A LOT OF DIALOGUE AROUND ENDING THE EPIDEMIC INITIATIVES WITH THE CITY OF PHILADELPHIA AND WE THINK WE NEED A LOT MORE MENTAL HEALTH SERVICES, WE NEED A LOT MORE SERVICES THAT DEAL WITH SUBSTANCE ABUSE. SO, THIS IS FINE BUT THERE'S AN EVEN HARDER TO REACH POPULATION THAT I SEE WHEN I'M ON THE MEDICAL SERVICE WHO GET HOSPITALIZED WITH UNCONTROLLED HIV. I DON'T THINK THOSE FOLKS WILL BE REACHED BY THIS INITIATIVE. >> I THINK IT WILL REACH THEM. WHETHER THEY CAN DO A TRIAL THAT WOULD CHANGE THEIR BEHAVIOR REMOTELY, MAYBE IT'S NOT POSSIBLE. BUT THEY CAN REACH THEM AND THEY CAN ENROLL THEM IN SOME OTHER TREATMENTS THAT WOULD BE EFFECTIVE. AS A WAY TO FIND PEOPLE, IT'S BEEN VERY SUCCESSFUL. I THINK THAT WILL HAPPEN. I'M NOT SURE THAT HOW THE CLINICAL TRIAL PART OF THIS WILL WORK. I MEAN, THAT'S RISKIER BUT AT LEAST THEY CAN FIND THEM AND GET THAT INTO A PROGRAM THAT WOULD HELP THEM. >> THERE ARE A BUNCH OF HANDS UP. I WANT TO LET CARL COMMENT AS DIRECTOR AND RICH I KNOW YOU HAD YOUR HAND UP. CARL, DO YOU WANT TO MAKE A COMMENT? >> YEAH, THIS IS A VERY IMPORTANT CONVERSATION AND IAN'S POINT NEEDS TO BE TAKEN VERY SERIOUSLY. AND THE POINT OF THIS INITIATIVE IS RESEARCH. THIS IS NOT FOR DELIVERY OF CARE LONG-TERM. SO WE NEED TO FIGURE OUT SOMETHING THAT WORKS. SO, WHAT WE NEED IS A STRATEGY. WE TEST SOMETHING LIKE LIGHT V.S. AND OTHER STRATEGIES TO LINK TO IT OR OTHER MEANS. AND I THINK WE NEED TO SEE THIS AS A STARTING POINT NOT SNAG IS JUST TO GO SUCCESSFUL OUT OF THE GATE. IF WE GET REALLY GREAT APPLICATION THAT'S WE CAN ALWAYS FUND MORE AND IF IT NEEDS TO BE TWEAKED, WE CAN COME OUT WITH THE R.F.A. AGAIN IN FUTURE YEARS. I THINK THAT THE CONVERSATION SHOULD BE ABOUT DOES THIS RESEARCH NEED TO BE DONE AND DOES IT NEED TO BE DONE QUICKLY? THE ANSWER SEEMS TO BE A RESOUNDING YES SO I WOULD SAY WE NEED TO COME BACK TO THIS TIME AFTER TIME AND LET'S JUST FOR THE SAKE OF NOT BLOWING OUR AGENDA, OUT OF THE WATER, WE'RE ALREADY EATEN UP THE 10 MINUTES WE SAVED, I WOULD SAY TAKE A FEW MORE COMMENTS, HAVE PEOPLE VOTE BUT KEEP IN MIND THIS HAS TO BE SEEN AS A POINT IN TIME THAT WE CAN GROW FROM AND YES, WE NEED MORE BUT WE NEED MORE IDEAS, NOT JUST A LOT MORE IN THIS -- MAYBE THIS IS THE RIGHT IDEA, MAYBE IT'S NOT. I THOUGHT IAN'S POINT WAS INCREDIBLY IMPORTANT. >> THANK YOU. I KNOW WE DID USE UP THE TIME WE SAVED. RICH HAS HAD HIS HAND UP SO THE LAST COMMENT BY RICH AND THEN ELAINE, IF YOU CAN PUT YOURS IN THE CHAT THAT WOULD BE GREAT. >> I JUST WANTED TO THROW OUT A SUPPLEMENTAL IDEA IN RESPONSE TO MAYBE THE RFA CAN ENCOURAGE COMMUNITIES WITH LIBERIA LIBRARIES WHERE PEOPLE CAN DROP IN AND USE A COMPUTER AT A KIOSK INSTEAD OF HAVING A CELL PHONE. >> THAT'S A GOOD IDEA. >> WE CAN INCLUDE THAT. >> OTHER PEOPLE HAVE COMMENTS, PLEASE, PUT THEM IN THE CHAT. I THINK THE FRUSTRATION WITH EFFECTIVE MEDS AND LACK OF SUPPRESSION THAT WE ALL SEE AND EXPERIENCE IN OUR PATIENTS AND FRIENDS IS SPEAKS TO THE INTEREST IN THIS SO, THANK YOU. SO IF PEOPLE CAN PUT THEIR HANDS DOWN I THINK, CARL, IAN, I DON'T THINK WE HAVE MORE QUESTIONS, THAT WOULD BE GREAT. WE ARE GOING TO MOVE TO THE LAST CONCEPT PRESENTED BY Dr. DIANNE LAWRENCE. AND SO IF THOSE, HER SLIDES CAN COME UP ENTITLED ENHANCING HIV RESERVOIR SUSCEPTIBILITY TO ELIMINATION. Dr. LAWRENCE, THANK YOU. >> THANK YOU SO MUCH, GOOD AFTERNOON, EVERYBODY. I'M DIANNE LAWRENCE A PROGRAM OFFICER IN THE BASIC SCIENCE PROGRAM. RYAN, CAN YOU GIVE ME CONTROL? I'M TRYING TO MOVE THE SLIDES. SO, THE PURPOSE OF THIS INITIATIVE ENHANCING HIV RESERVOIR SUSCEPTIBLE TO ELIMINATION IS TO UNDERSTAND WHY PERSISTENT HIV RESERVOIR CELLS ARE RESISTANT TO CELL DEATH AND IMMUNE CLEAR EVENS AND IDENTIFY TARGETS THAT COULD BE USED TO SEN SA TIES HIV-INFECTED CELLS TO ERADICATION. THIS IS A NEW INITIATIVE USING THE RO1 GRANT MECHANISM AND IT'S A ONE-TIME RFA WITH $2.5 MILLION SET ASIDE SO WE ANTICIPATED FUNDING THREE TO FIVE APPLICATIONS. THERE'S SEVERAL BARRIERS THAT MUST BE OVERCOME. FOR EXAMPLE, WE STILL DON'T COMPLETELY UNDERSTAND THE DYNAMICS THE HIV RESERVOIR INCLUDING WHAT DRIVES RESERVOIR FORMATION, MAINTENANCE AND DECAY, HOW THE RESERVOIR CHANGES OVER TIME, AND MECHANISMS ARE SPONTANEOUS REACTIVATION IN INFECTED CELLS. THE FREQUENCY OF PERSISTENTLY INFECTED CELLS IS VERY LOW. IT IT'S EXTREMELY STABLE WITH HALF LIFE OF 44 MONTHS AND THERE'S EVIDENCE THAT PROLIFERATION PLAYS A MAJOR ROLE IN COUNTERACTING HIV RESERVOIR DECAY BUT IT'S UNCLEAR WHICH DRIVERS OF PROLIFERATION MAY BE MOST INVOLVED. RECEIPT VOICE AND TISSUE COMPARTMENTS ARE DIFFICULT TO ACCESS AND THOUGHT TO BE PROTECTED FROM IMMUNE CLEARANCE. RESIDUAL OR DEFECTIVE VIRUS PRODUCTION MAY BE RECOGNIZED BY THE IMMUNE SYSTEM SO IT MAY SERVE AS A DECOY AND CONTRIBUTE TO CHRONIC IMMUNE ACTIVATION AND THIS TOGETHER WITH VIRAL ESCAPE MUTATIONS AND EXHAUSTION OF CELLS CAN RESULT IN A FAILURE OF IMMUNE CLEARANCE. FOR OVER A DECADE, THERE'S BEEN TREMENDOUS EFFORT TO OVERCOME THESE BARRIERS AND ELIMINATE THE RESERVOIR. ONE MAJOR APPROACH, IS KICK AND KILL OR SHOCK AND KILL, WHICH INVOLVES SEARCH FOR WAYS TO OVERCOME SILENCING MECHANISMS TO STIMULATE HIV-RNA AND ANTIGEN PRODUCTION AS WELL AS ANTIBODY-BASED OR CELLULAR STRATEGIES TO IMPROVE IMMUNE TARGETING FUNCTION. AND THE OVER ALL THE GOAL OF SUCH STRATEGIES WOULD BE TO INDUCE -- SORRY, I'M HAVING TROUBLE ADVANCING THE SLIDES. SO THE GOAL OF THESE STRATEGIES WOULD BE TO INDUCE CELLS BY VIRUS INDUCED SIGHT OWE TOXICITY OR IMMUNE CLEARANCE SO ALTHOUGH THERE'S BEEN AND EFFECT TER FUNCTIONS AND THESE STRATEGIES HAVE HAD LIMITED SUCCESS IN' RAID INDICATING THE HIV RESERVOIR. SO WE KNOW THAT SOME HIV INFECTED CELLS HAVE THE ABILITY TO SURVIVE AND PERSIST FOR YEARS, EVEN DECADES IN THE PRESENCE OF ART. AND SEVERAL STUDIES, MODELING STUDIES HAVE DEMONSTRATED A WIDE RANGE OF SURVIVAL TIMES IN INFECTED CELLS AND THE REASON FOR THIS ARE NOT CLEAR. IT MAY BE THAT CHANGES IN THE HOST ENVIRONMENT ALLOW FORMATION OR STABLATION OF A LONGER LEAF RESERVOIR BUT THEY ARE COMPLETELY UNKNOWN. AND THEY DAMPEN EFFECT TER FUNCTION AND ENRICHED IN RESERVOIR CELLS AND IT'S BEEN PROMISING AS A STRATEGY FOR CANCER AND THERE'S BEEN HOPE THAT A SIMILAR STRATEGY WOULD IMPROVE HIV RESERVOIR ERADICATION BUT EVEN CLINICAL STUDIES OF COMBINATION IMMUNE CHECK POINT BLOCKERS THAT EFFECTIVELY REACTIVATE HIV AND ENHANCE CTL FUNCTION HAVE SHOWN NO CONSISTENT EFFECT ON REDUCING THE SIZE OF THE LATEN RESERVOIR. AND OTHER STRATEGIES HAVE BEEN DEMONSTRATED TO INDUCE LATEN SEE REACTIVATION AND BOOST FUNCTIONAL HIV SPECIFIC IMMUNITY IN HUMANIZED MOUSE AND NON HUMAN PRIMATE MODEL HAVE ELIMINATED THE INFACT REPLICATION RESERVOIR. AND IN HUMAN PRIMARY THE REACTIVATION COMBINED WITH FUNCTIONAL CD8T-CELLS PAILS TO DEPLETE THE VIRUS AND I -- THESERESULTS HI GHLIGHTED NEED TO BETTER UNDERSTAND THE MECHANISM OF RESERVOIR SURVIVAL AND RESISTANCE TO ELIMINATION AND ANOTHER APPROACH MAY BE NEEDED TO MAKE PERSIST APTLY INFECTED CELLS MORE SUSCEPTIBLE TO DEATH AND CLEARANCE BY EITHER KICK AND KILL OR OTHER STRATEGIES TO ERADICATE HIV RESERVOIRS. SEVERAL HIV PROTEINS CAN EITHER UP OR DOWN REGULATE MULTIPLE PRO AND ANTI PATHWAYS AND THESE VERY COMPLEX INTERACTIONS CAN EXPLAIN MECHANISMS PROMOTING SURVIVAL AND PROLIFERATION OF THESE RESERVOIRS DESPITE VIRUS EXPRESSION THAT IS EXPECTED TO KILL THE CELLS. FOR EXAMPLE, HIV PRO TEE ACE TO GENERATE AP41 WHICH ACTIVATES BACK AND DUCES INFECTED CELLS AND IN CELLS WHERE EXPRESSION OF THE PRO SURVIVAL OR MOLECULE BCL2 IS HIGH, AP41 BINDS BCL2 AND CELL DEATH DOES NOT OCCUR. SO WE HAVE NO IDEA HOW THE BALANCE OF THESE PATHWAYS MAY DIFFER IN PRIMARY INFECTION VERSUS PERSISTENTLY INFECTED CELLS, IN DIFFERENT RESERVOIR CELL SUB TYPES OR FOLLOWING SPONTANEOUS ROW ACTIVATION VERSUS REACTIVATION AGENTS. THE PRO SURVIVAL FACTORS BCL2 AND BERC5 ARE ENRICHED IN PRIMARY T-CELL AND BLOCKING THESE FACTORS INCREASE CELL DEATH FOLLOWING STIMULATION OF VIRUS PRODUCTION. THESE ANTAGONIST ALSO REDUCE PROLIFERATION OF INFECTED CELLS POINTING TO A ROLE FOR THESE PATHWAYS IN EXPANSION OF THE RESERVOIR. HIV RESERVOIRS ALSO HAVE MECHANISMS TO RESIST IMMUNE CURRENTS AND IT'S KNOWN THAT THE HIV ACCESSORY PROTEINS CONTRIBUTE TO REDUCTIONS IN SURFACE EXPRESSION AND RECOGNITION BY CELLS AND A RECENT STUDY SHOWS THAT NEF INHIBITION RESTORED HIV-SPECIFIC CTL CLEARANCE INVITO. ALSO PRESENT AT A RECENT STRATEGY FOR HIV CARE MEETING AT HIV, SUGGESTED THAT ANTIGEN PROCESSING COULD BE A LOTTERED IN PERSISTENTLY EFFECTED CELLS. A STUDY OF ELITE CONTROLLER FOUND GREATER SENSITIVITY OF CTL COMPARED TO RESERVOIRS FROM SUPPRESSED INDIVIDUALS NAIVE AND TERMINALLY DIFFERENTIATED SUBSETS AND THE ENHANCED SENSITIVITY CORRESPONDENT TO A REDUCED RESERVOIR SIZE. IN A STUDY OF CTL RESISTANT HUMAN HIV RESERVOIR CELLS X VIVO TREATMENT WITH A DETAIL TO ANTAGONIST MADE THEM SENSITIVE TO ELIMINATION BY ANTAGOLOGITT CELLS AND FINALLY, NEWER TECHNOLOGIES SUCH AS SINGLE-CONTROL OMICS TECHNOLOGIES HAVE IDENTIFIED PRO SURVIVAL GENE EXPRESSION SIGNATURES IN REACTIVATED RESERVOIR CELLS EXPRESSING FULL LENGTH INTACT HIV AND THESE PATTERNS SHOWN HERE, THEY WERE DISTINCT FROM BOTH PRODUCTIVELY INFECTED AND UNINFECTED CONTROL CELLS. SO, OVER ALL THESE FINDINGS ARE CONSISTENT WITH THE IDEA THAT REACTIVATED RESERVOIRS MAY PRODUCE FACTORS THAT ALLOW SURVIVAL AND EXPANSION WHILE BEING REFACTORY TO CELL DEATH SIGNALS TRIGGERED BY HIV REPLICATION AND IMMUNE TARGETING. SO, SOME KEY SCIENTIFIC QUESTIONS THAT COME FROM THIS RESEARCH INCLUDE WHAT CELLULAR MECHANISMS IMPACT SUSCEPTIBLE OF THESE RESERVOIRS TO VIRUS OR IMMUNE CELL DEATH UPON EITHER SPONTANEOUS REACTIVATION OR DELIBERATE THERAPEUTIC INTERCEPTIONS TO REACTIVATE THE RESERVOIR. IT'S INVOLVED IN HIV RESERVOIR SURVIVAL AND EXPANSION AND HOW DOES ANTIGEN EXPRESSION DIFFER IN REACTIVATED RESERVOIR VERSUS PRIMARY INFECTION AND HOW DO FACTORS AND TRANSCRIPTIONAL REGULATIONS IMPACT THE RESPONSE TO DEATH SIGNALS IN VARIOUS BLOOD AND TISSUE RESERVOIR CELLS AND CELL SUB TYPES. CURING HIV IS A MAJOR PRIORITY FOR NIH AND FINDINGS WAYS TO BUY PASS SURVIVAL MECHANISM TO PRIME RESERVOIRS WOULD MAKE THEM MORE SENSITIVE TO MULTIPLE STRATEGIES FOR ERADICATION. SO THE OBJECTIVES OF THIS INITIATIVE ARE TO' LOOSE DATE COMPLEX MECHANISMS ARE SURVIVAL AND -- TO ENHANCE ERADICATION APPROACHES. RESEARCH AREAS OF INTEREST WOULD INCLUDE EXPANSION OF BLOOD AND TISSUE RESERVOIRS. APPROACHES TO COUNTERACT DOWNREGULATION OF MHC OR IMPAIRED ANTIGEN PRESENTATION. IDENTIFICATION OF FACTORS IN THE CELLULAR MICRO ENVIRONMENT THAT MIGHT INHIBIT RESERVOIR ELIMINATION. THERAPEUTIC STRATEGIES COULD BE INCLUDED TO TEST SPECIFIC MECHANISTIC HYPOTHESIS. THEY WOULD BE ALLOWED IN THESE STUDIES. AND WHAT WOULD NOT BE SUPPORTED WOULD BE STUDIES THAT ARE FOCUSED PRIMARILY ON IMPROVING LATEN SEE ACTIVATION OR ENHANCING SUB KILLING SO THIS IS NOT ABOUT IMPROVING SHOCK AND KILL, THIS IS ABOUT TARGETING THE RESERVOIRS THEMSELVES AND REEREALLY UNDERSTANDING WHY THEY ARE SURVIVING AND NOT BEING SUSCEPTIBLE TO THESE SIGNALS. THEY DO NOT EXTEND TO PRIMARY CELLS FROM HIV OR SIV INFECTED HOSTS SO IF IT'S LIMITED TO CELL LINES THAT WON BE APPROPRIATE AND APPROACHES THAT BY PASS CELLULAR MECHANISMS WOULD NOT BE APPROPRIATE FOR THIS INITIATIVE AND CLINICAL TRIALS WOULD NOT BE ALLOWED. THIS CONCEPT IS COMPLIMENTARY TO OUR EXISTING HIV PORTFOLIO INCLUDING THE MARTIN DELANEY AND THE NEWLY AWARDED INCLUDE A FOCUS ON DEVELOPMENT OF EFFECTIVE STRATEGIES FOR HIV ERADICATION AND THEY DON'T HAVE A SPECIFIC FOCUS ON SUN ACCEPTABILITY OF THESE RESERVOIRS TO CEL CELL DEATH. WE ALSO HAVE THE UNDERSTANDING HIV RESERVOIR DYNAMICS RFA WHICH IS CURRENTLY UNDER REVIEW. THESE PO1s WOULD SUPPORT RESEARCH TO BETTER UNDERSTAND RESERVOIR ESTABLISHMENT, MAINTENANCE AND REBOUND BUT THEY DON'T SPECIFICALLY ADDRESS MECHANISMS OF CELL DEATH. SO, WE GREATLY APPRECIATE THE FEEDBACK FROM THE DOCTORS AND WHO RECOMMENDED APPROVAL OF THIS CONCEPT AND THEY FELT A FOCUS ON SPECIFIC REASONS FOR SURVIVAL OF VES VOYEURS AND PUSHING THOSE CELLS TOWARDS DEATH IS GREATLY NEEDED AND JUSTIFIED BY RECENT STUDIES. THEY RECOMMENDED THE SCOPE SHOULD FOCUS ON CELL-MEDIATED MECHANISMS OF DEATH AND SHOULD NOT INCLUDE APPROACHES SUCH AS TOXINS THAT ARE TARGETING THE VIRUS-EXPRESSING CELLS BY PASSING CELLULAR MECHANISMS AND WE AGREE AND HAVE INCORPORATED THIS INTO WHAT WILL NOT BE SUPPORTED. THEY ALSO SUGGESTED THAT IN ADDITION TO THE IMMUNE CLEARANCE MECHANISMS, EXPLORING WHY THE CONTEXT OF ART DO NOT INDUCE CELL DEATH WOULD BE IMPORTANT SO WE AGREE AND HAVE TRIED TO EMPHASIZE THE DISTINCT RATIONALE FOR STUDYING BOTH THE VIRUS AND IMMUNE BASED CELL DEATH MECHANISMS. THE REVIEWERS RECOMMENDED THAT IT WOULD BE IMPORTANT TO EMPHASIZE HOW THE GOAL FOR THIS PROGRAM WOULD BE DISTINCT FROM OTHER ERADICATION STRATEGIES THAT HAVE NOT BEEN SUFFICIENT. I'VE TRIED TO CLARIFY THIS IN THE OBJECTIVES AND THE DIAGRAM THAT THIS GOAL IS DEVELOPING THIS EXTRA STEP TO MAKE THESE OTHER STRATEGIES MORE EFFECTIVE. THEY FELT THAT TREATMENT STRATEGIES SHOULD BE ALLOWED AS TOOLS TO TEST HYPOTHESIS BUT NOT REQUIRED AND NOT INCORPORATED INTO THE PURPOSE SO WE'VE REFINED THE PURPOSE AND SCOPE TO CLARIFY THAT POINT AND FINALLY, THEY FELT IT WOULD BE OF INTEREST TO STUDY IF SUCH CELLULAR MECHANISMS CONTRIBUTE TO THE LONGEVITY OR THE EXPANSION OF INFECTED CELLS AND WE'VE INCLUDED THAT IN THE SCOPE OF THIS INITIATIVE. AND THIS BRINGS ME TO THE FINAL SLIDE AND I'M HAPPY TO TAKE ANY QUESTIONS. THANK YOU. >> GREAT. THANK YOU, Dr. LAWRENCE, VERY NICE PRESENTATION. REALLY IMPORTANT SUBJECT. THANK YOU. QUESTIONS, COMMENTS OR THOUGHTS THAT PEOPLE HAVE? I WILL REITERATE HOW TIMELY THIS IS AND HAD HELP US REACH THE COAL CURE. >> THANK YOU. ANY COMMENTS? >> LET ME THEN -- I DON'T SEE ANY OTHER COMMENTS. THANK YOU, AGAIN, Dr. LAWRENCE, APPRECIATE YOUR PRESENTATION. LET ME ASK PEOPLE TO VOTE. I NEGLECTED TO ON THE LAST PRESENTATION, I ALWAYS NEGLECT ANEGLECTAT LEAST ONE IT WAS Dr. SHARP'S PRESENTATION TODAY. SO IF PEOPLE CAN MAKE SURE THAT THEY VOTE ON ALL FOUR OF THE PRESENTATIONS, AND MAKE SURE YOU GET THAT GREEN LIGHT THAT YOUR VOTE IS SAVED, THAT WOULD BE GREAT. WE'VE CUT BACK UP ON OUR TIME. BEFORE I TURN IT BACK TO YOU, LET ME JUST MAKE ONE COMMENT THAT I FEEL LIKE I MAKE EVERY MEETING. IF I DO I'M GOING TO MAKE IT AGAIN TODAY, WHICH IS IT'S REMARKABLE TO LISTEN TO THESE FOUR PRESENTATIONS RANGING FROM THE ATOMIC AND MOLECULAR LEVEL TO THE APPS THAT WE CAN USE AND WHETHER PUBLIC LIBRARIES COULD HELP WITH VIRAL SUPPRESSION. THE BREADTH OF SCIENTIFIC EXPERTISE, WITHIN THE WALLS OF NIAID DIVISION OF AIDS IS REMARKABLE. THOSE OF US WHO ARE ON THE COMMITTEE, ARE REGULARLY IMPRESSED AT THESE MEETINGS AS YOU ALL THINK ABOUT HOW TO SUPPORT AND INSTIGATE THE BEST RESEARCH TO ANSWER THESE CRITICAL QUESTIONS AND IT MAY BE 40 YEARS LATER, THE QUESTIONS ARE ONLY MORE INTERESTING AND COMPELLING, THEY'RE NOT LESS. SO I JUST REALLY, I THINK TODAY, WE REALLY SAW THIS IN A REMARKABLE WAY. I WANTED TO THANK EVERYONE FOR NIAID AND THE DIVISION OF AIDS ON BEHALF OF THE COMMITTEE AND I SEE PEOPLE APPLAUDING AND AGREEING WITH ME. CARL, LET ME HAND IT BACK TO YOU WITH A MINUTE LEFT. >> THANK YOU FOR YOUR NICE WORDS, KEN. AGAIN, WE ALL FEEL THE DAILY CHARGE OF NOCHALLENGE OF NOT HAVING A SAFE VACCINE AND NOT USING THE PREP TOOLS WE HAVE OR THE THERAPEUTIC TOOLS WE HAVE AND TAKE IT VERY SERIOUSLY AND ONLY THROUGH RESEARCHERS LIKE YOURSELF AND PEOPLE ON THE COMMITTEE, WHO ACTUALLY DO THE WORK, WE NEED TO MAKE SURE YOU ARE ARMED WITH THE TOOLS TO GO OUT THERE AND SOLVE THE PROBLEMS. SO, IT'S A PARTNERSHIP. >> IT IS A PARTNERSHIP HERE. WE ARE ALL IN AGREEMENT THERE. SO, I THINK WE ARE SET. AGAIN, EVERYONE, PLEASE VOTE ON THESE FOUR INITIATIVES. WE WILL SEE EACH ON ZOOM IN JANUARY. HOPEFULLY WE WILL START TO SEE EACH OTHER IN-PERSON MORE FREQUENTLY IN INCREASING WAYS. I WANT TO THANK AGAIN AGAIN FOR ALL OF THEIR EFFORTS. AND TAKE CARE. BE WELL.