Sponsored by NIH/NIAID/DAIDS Completed Observation of the Randomized Placebo-Controlled Phase of iPrEx with co-funding by the Bill & Melinda Gates Foundation and drug donated by Gilead Sciences Grant et al, IAS Rome 2011

MSM and Trans women Randomized 1:1 daily oral PrEP FTC/TDF vs placebo Prevention services provided to all Followed monthly on drug for:  HIV seroconversion  Adverse events (especially renal & liver)  Metabolic effects (bone, fat, lipids)  HBV flares among HBsAg+  Risk behavior & STIs  Adherence  If infected ‣ Drug resistance ‣ Viral load ‣ Immune responses & CD4 count The iPrEx Study New England Journal of Medicine, online Nov 23, 2010

Intention to Treat – Primary Analysis (May 1, 2010) Intention to Treat – Final Analysis (Aug 2010) Post Stop - Analysis (Nov 21, 2010) Final DEXA/HBV Visit (February 28, 2011) iPrEx Timeline 30 Jun Sept Dec Mar Jun Sept Dec Mar Jun Sept Dec Mar Jun Sept Dec Feb 11 Enrollment Grant et al, IAS Rome 2011

Fully enrolled as of December 2009 Lima Iquitos Guayaquil Sao Paulo Rio de Janeiro Boston San Francisco Cape Town Chiang Mai Sites11 Participants2499 New England Journal of Medicine, online Nov 23, 2010

Efficacy (MITT) 42% (18-60%) Through End of Study Infection Numbers: 83 – 48 = 35 averted P = Grant et al, CROI Boston 2011

EfficacyP Value Age <25 years 28% ≥25 years 56% p=0.18 Ethnicity Hispanic 40% Non-Hispanic 52% p=0.63 Region Andes 41% Non-Andes 49% p=0.75 Schooling <Secondary 14% ≥Secondary 52% p=0.16 Alcohol (on days drank) <5 drinks 48% ≥5 drinks 43% p=0.81 Circumcision No 36% Yes 83% p=0.10 Trans Identity or Feminizing Hormones No 49% Yes -3% p=0.14 Unprotected Receptive Anal Intercourse No URAI -25% URAI 52% p=0.03 Efficacy of Oral FTC/TDF PrEP Subgroups Grant et al, IAS Rome 2011

Oral FTC/TDF Prophylactic Activity Cases HIV+ Controls* HIV- N48144 TNF-DP (cells)9%36% TFV (plasma)8%40% FTC-TP (cells)11%41% FTC (plasma)8%40% Any Drug10%44% * Matched on site and time on study. -92% reduction in HIV risk associated with drug detection at the timepoint nearest first evidence of infection. -Analysis adjusted for age, URAI baseline and follow-up, schooling, BMI. Anderson et al, IAS, Rome 2011

Drug Detection in Hair N=128N=94 Correlates to dose (DOT) Liu CROI 2011 Opt-in substudy o Not case matched o 100 hairs cut o FTC and TNF Higher detection in… o Older persons o US/SA Lower detection in… o Trans-identified Liu et al, IAS, Rome 2011

Unprotected Receptive Anal Intercourse p=0.30

Perceived Drug Assignment Believe they are on... Randomized to FTC/TDFPlacebo 115 (9%)108 (9%) Don’t Know 791 (63%)784 (63%) Truvada 275 (22%)278 (22%) No CASI 67 (5%)81 (7%) Based on Week 12 CASI p=0.89 New England Journal of Medicine, online Nov 23, 2010

Those who believed they were taking FTC/TDF p=0.44 Unprotected Receptive Anal Intercourse

Acute HIV Infection p=0.004 for Placebo p=0.002 for FTC/TDF Visits Antibody- HIV RNA+ Percent of Visits Fold Change (95% CI) Enrollment2, %Ref Follow-up: Placebo 11, % -3.8 (-1.5 to -9.5) Follow-up: FTC/TDF 11, % -6.5 (-2.2 to -20.2)

Provide post-trial access in accordance with the Declaration of Helsinki and Good Participatory Practices. Learn from PrEP users about implementation issues. Learn if PrEP use increases when people know the tablet is safe and effective and not a placebo. Learn what happens with sexual practices. Learn if every 12 week monitoring Is sufficient. The Aims:

Status on July 20, 2011 SiteStatus San FranciscoEnrolling BostonEnrolling Cape TownEnrolling ChicagoExpected Aug ’11 Brazil x 3Expected Aug ’11 Chiang MaiExpected Aug ’11 EcuadorExpected Aug ’11 PeruUnder IRB Review

Conclusions Oral FTC/TDF PrEP provides additional protection against the acquisition of HIV infection among MSM receiving a comprehensive package of prevention services. Detectable drug is associated with a 92% reduction in HIV risk after adjusting for other benefits. There is no evidence for risk compensation even among those who thought they were taking FTC/TDF. Oral FTC/TDF use was nearly 90 to 100% at some sites; Lower at other sites; Hair is promising for monitoring.

iPrEx ABSTRACTS AT IAS, Rome 2011 #ABSTRACT # PRIMARY AUTHOR ABSTRACT TITLEFORMAT PRESENTATION DATE 1MOLBPE035RM. Grant Acute Pre-seroconversion HIV Infection at Baseline Prior to Starting Oral or Topical Pre-Exposure Prophylaxis: iPrEx and CAPRISA 004 PosterJuly 17th 2MOLBPE043M. Merhotra Local Risk Indicators Key for Targeting PrEP PosterJuly 17th 3MOLBPE037A. Liu Hair as a biological marker of daily oral pre-exposure prophylaxis (PrEP) adherence and tenofovir/emtricitabine (TFV/FTC) exposure in the Global iPrEx Study PosterJuly 18th 4MOLBPE039P. Goicochea Social Adverse Events Experienced by Trans Women and Other Men who Have Sex with Men (MSM) Participating in a HIV Pre-Exposure Prophylaxis (PrEP) Trial PosterJuly 18th 5MOPE393P. Goicochea Strategizing Communications for Successful Dissemination of Study Results in HIV Prevention Trials: The case of the iPrEx Study July 18th 6MOLBPE034P. Anderson Expanded case-control analysis of drug detection in the global iPrEx trial PosterJuly 18th 7TULBPE024A. Liu Depression among men who have sex with men (MSM) at risk for HIV infection in the Global iPrEx Study PosterJuly 19th 8TUPE363H. Gilmore Adherence/Drug Detection Rates and Study Participant Experiences of Counseling Support among MSM in the iPrEx pre-exposure prophylaxis (PrEP) trial in San Francisco, United States PosterJuly 19th 9WELBC04RM. Grant Completed observation of the randomized placebo-controlled phase of iPrEx: daily oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who have sex with men OralJuly 20th 10CDC214J. McConnell Forgotten Risk, Remembered Sex: Standard HIV Risk Questions Underestimate Sex in Networks E-poster 11CDB467P. Gonzales Low Bone Mineral Density in Peruvian Young Men at High Risk for HIV Infection: Risk Factors E-poster

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