Protection against hiv sterilizing immunity

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protection against HIV sterilizing immunity! protection against disease A reduced HV peak and “set point” initial infection “controlled” chronic infection with low set point Transmission Vaccine Success Cell-Mediated Immunity
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This CHAVI web site is at
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Antiretroviral Therapy Effect on HIV Transmission ?
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Trends in reduction of MTCT The Effect of Antiretroviral Therapy McIntyre J, et al. 12th CROI, Boston 2005, #8 USA & Europe Thailand Africa % Transmission 0 5 10 15 20 25 30 35 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
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ART to Prevent Sexual Transmission of HIV Post-exposure prophylaxis (nPEP) USPH Guidelines 2005 Pre-Exposure Prophylaxis (PREP) Treatment of the infected person
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US ALGORITHM FOR nPEP USAGE Significant exposure risk Negligible exposure risk < 72 hours >72 hours since exposure Source patient Known to be HIV+ Source patient of unknown HIV status nPEP recommended Case-by-case determination nPEP Not recommended
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Pre Exposure Prophylaxis!!
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0 2 4 6 8 10 12 14 0 25 50 75 100 Number of rectal exposures % Uninfected animals Controls (n = 18) Injectable FTC (n = 6) Injectable Truvada (n = 6) Oral Truvada (n = 6) Oral TDF (n = 4) PrEP in Macaques Garcia-Lerma et al PLoS Medicine in press Garcia-Lerma et al PLoS Medicine in press Cohen and Kashuba PLoS Medicine inn press (editorial) Cohen and Kashuba PLoS Medicine inn press (editorial)
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Current and Proposed PrEP Trials Current and Proposed PrEP Trials Coitally-dependent TNF Gel Daily TNF Daily Truvada Daily TNF Gel
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Topical HIV-1 Prevention Klasse et al  Annu Rev Med 2008 Klasse et al  Annu Rev Med 2008 , July 2008 Tenofovir Gel Reservoir and Matrix Vaginal Rings Candidate Status - Phase PRO 2000 Ongoing – Phase 3 Tenofovir gel Ongoing – Phase 2B PRO 2000/BufferGel® Ongoing – Phase 2/2B Dapivirine Ongoing – Phase I Ethanol in Emollient Gel Ongoing – Phase I UC-781 Ongoing – Phase I VivaGel® Paused – Phase I ACIDFORM ™ Planned – Phase 3 Invisible Condom™ Planned – Phase 2/3 CAP vaginal soft tablet Planned – Phase I Duet® Planned – Phase I PC-815 Planned – Phase I Current Microbicide Candidates (listed in latest stage of development)
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Where Are We Going III Treatment Must Marry Prevention
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HIV-RNA HIV-RNA HIV-DNA HIV-DNA 0 20 20 40 40 60 60 80 80 100 100 Patients (%) with Patients (%) with detectable HIV in semen detectable HIV in semen n=55 n=55 n=114 n=114 Controls (drug naive) Controls (drug naive) Potent ART Potent ART p<0.0001 p<0.0001 p=0.025 p=0.025 Semen HIV with HIV Treatment Semen HIV with HIV Treatment Vernazza, Cohen Vernazza, Cohen et al., et al., AIDS, 2000 AIDS, 2000
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0 10 20 30 40 50 0 3 6 9 12 18 24 30 36 Months on ART Estimated HIV transmission risk after 3 years of ART (per 1000 PYRs) 1 spouse sero-converted in year 1; none in years 2 and 3
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The Hierarchy of Transmission Risk.. From ~39 Million People with HIV Established infection on ART  Established infection untreated  Established infection,  untreated + STD  Acute HIV Infection  INCREASING RISK 2.5 million people 2.5 million people 30,000,000 people 30,000,000 people ( ( Fraser et al, PNAS, 2007) Fraser et al, PNAS, 2007) ?
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