IAS Members Meeting July 19th 2011 Achievements and learning over the past 30 years: what do we need next? Françoise BARRÉ-SINOUSSI Regulation of Retroviral Infections Unit Department of Virology

30 years of HIV/AIDS Science: Main milestones Understanding the biology and pathogenesis of HIV infection: First step toward prevention and treatment strategies…. Number of people living with HIV (million) AIDS HIV-1 Identification HIV-1 Sequence HIV-1 Diversity HIV-2 Identification HIV-1 subtypes HIV-1 O Recombinants VIH-1 Origin of HIV HIV-1 N HIV-1 P CD4 Receptor Co-receptors HIV Reservoirs CD4 Depletion in gut Immune activation Innate response HIV Restriction factors HIV controllers Microbial Translocation SIV 10 11

30 years of HIV/AIDS translational science… 6,6 million Prophylactic and therapeutic vaccine researchTherapy and prevention research Number of people under HAART in LMIC AZT therapy HIV Testing Circumcision (60%) 1st phase I trial ARV Resistance HIV Quantification PMTCT Vaccine therapy VaxGen Trial STEP Trial RV144 trial ARV as prevention (Caprisa, Iprex) HPTN 052 First RDT Protease inhibitor HAART Integrase & CCR5 inhibitor Fusion inhibitor 6 5 UNGASS Number of people annually infected with HIV Global Fund 2,5 million Number of AIDS related death in LMIC 1,7 million IAS AIDS HIV

Dates Clinical efficacy studies StrategyViral targets Immune response Efficacy AidsVax Protein subunit (AIDSVAX) monomeric rgp120 Type specific binding Ab NO Step Phambili Viral vector (Ad5) gag/pol/nef CD8+T (+++)NO RV144 (Thai trial) Prime: ALVAC- vCP152 + Boost: AIDSVAX gag/pol/env + Monomeric rgp120 B/E CD4+ T cell (+/-) + Type specific binding Ab 31% reduction Lessons from Vaccine trials

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EDUCATION CONDOMS TREATMENT AS PREVENTION DRUG ALCOHOL TREATMENT TESTING COUNSELING STI TREATMENT MICROBICIDES CIRCUMCISION PrEP HARM REDUCTION HIV CURE VACCINE Evidence based Prevention Implementation of combined tools Highly active HIV prevention tools

Early Events in HIV infection are critical Early pathogenic events: Inflammation/activation & reservoirs Critical for vaccine and cure research…

How HIV persist during therapy Better knowledge of viral and host factors implicated in establishment of HIV reservoirs and in HIV persistence - Ongoing viral replication occurs insubject on suppressive HAART (TW Chun JCI; N Tobin, J Virol 2005) - HIV integrate in long lived resting memory T cells and persist despite suppressive HAART (TW Chun, Nat Med 1995; D Finzi, Science; TW Chun PNAS 1997) - Reservoir cells, like other memory T cells, divide very slowly to maintain the memory of the immune system (A. Bosque and V. Planelles) T cell survival Proliferation Viral replication Courtesy of Nicolas Chomont

A decrease in viral load is clearly associated with clinical benefit Proof of concept from the Berlin patient (bone marrow transplant of CCR5  32 stem cells) A small percentage (<0.3%) of HIV-1-infected subjects show no disease progression and/or spontaneous control of viral replication (e.g. long- term nonprogressors and “HIV Controllers”) African NHP infected by SIV are naturally protected against disease progression Why it should be possible to obtain at least functional cure for HIV/AIDS? It is time to engage in research towards an HIV Cure Definition: Permanent suppression of viral replication without eradicating the virus from the body => Long-term remission + Prevention

From C. Katlama

“Towards an HIV Cure” Global Scientific Strategy Sign-on the Rome Statement for an HIV Cure: