1. What can we learn from diverse spectrum of HIV/SIV infections? Françoise BARRÉ-SINOUSSI Regulation of Retroviral Infections Unit Department of Virology Lecture at Academia Sinica 06 th October 2010 - Taiwan

2. Therapy and prevention researchProphylactic and therapeutic vaccine research Number of people living with HIV (million) 35 25 15 5 19808182 83 848586 87 888990 91929394 95969798 99 00010203 04 0506070809 HIV biology and pathogenesis HIV-1 Identification HIV-1 Sequence HIV-1 Diversity Identification VIH-2 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 HIV Restriction factors HIV controllers Microbial Translocation HIV testing AZT Therapy PMTCT HAART Vaccine therapy Circumcision (risk reduction) AIDS 1st phase I trial VaxGen Trial STEP Trial « Thaï » trial SIV HIV Quantification ARV Resistance African epidemic M. Müller-Trutwin & F. Barré-Sinoussi Main milestones in 27 years of research on HIV

3. HIV Vaccine history August 1987 1st phase I trial 2003 Data of the 1st phase III efficacy trial VaxGen Lack of efficacy of rgp120 definitively proven 1987-2007 > 110 trials (10 Phase II/III) with 67 products (27 500 volunteers) Candidate vaccine are usually safe and showed some degree of immunogenicity Sept. 2007 STEP/Phambili phase IIb trial (HIV-1B gag, pol, nef / rAd5) Discontinued for lack of efficacy RV144 “Thaï”: ALVAC (gag/pol/env) + AidsVax (B/ErGp120) Oct. 2009 Ongoing phase II trials (DNA+MVA, DNA+NYVAC, lipopeptides…) Modest Efficacy 31%

4.  Animal model limitations  Genetic Variability of HIV  Viral evasion of the immune system  Early establishment of viral reservoirs  Mechanisms of protection still undefined ???  Cell to cell transmission of the virus  HIV infects and alters key players of the immune system  Very rapid induction of dysfunctions in both innate and adaptative immune responses Défis scientifiques du vaccin (2) Think differently according to the knowledge pathogenesis 27 years after the discovery of AIDS virus, urgent need for a new vaccine strategies…