HPTN 052. Myron S. Cohen, MD Principal Investigator. Presented at the 6 th Int. Workshop on HIV Transmission, July 2011, Rome, Italy

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1 HPTN 052 Myron S. Cohen, MD Principal Investigator Presented at the 6 th Int. Workshop on HIV Transmission, July 2011, Rome, Italy

2 Antiviral Treatment as Prevention Extensive biological plausibility The concentration of HIV-1 in blood and genital tract correlates with sexual transmission Antiretroviral agents that concentrate in the genital tract reduce HIV-1 VL Most observational reports indicate ART reduces transmission of HIV-1 in couples

3 HPTN 052: Study Objectives/Goals To evaluate the effectiveness of ART to prevent the sexual transmission of HIV in serodiscordant couples To evaluate the optimal time to initiate ART in order to reduce morbidity and mortality

4 HPTN 052 Study Design HIV+ subjects with CD4 350 to 550 cells/µl 1763 serodiscordant couples Immediate ART CD Randomization HAART Delayed ART CD4 <250 Endpoints: i) Transmission Events ii) OIs, other Clinical Events-WHO 2,3,4 & Death iii) ART Toxicity

5 HPTN 052 Timeline: The Fast Track? ART for prevention of HIV HPTN 052 Protocol Development ACTG 5175 Requirement HPTN 052 Drug Procurement HPTN 052 Pilot HPTN 052 Enrollment HPTN 052 DSMB (#10) April 28, 2011

6 HPTN 052 Enrollment Region Site Couples Americas (278) Asia (531) Africa (954) Porto Alegre, Brazil 90 Rio de Janeiro, Brazil 186 Boston, United States 2 Chennai, India 250 Pune, India 175 Chiang Mai, Thailand 106 Gaborone, Botswana 77 Kisumu, Kenya 60 Blantyre, Malawi 230 Lilongwe, Malawi 251 Johannesburg, South Africa 46 Soweto, South Africa 50 Harare, Zimbabwe 240 Total 1763

7 DSMB April 28 Recommendation VERBATIM: The Board recommends that the results of the trial be announced as soon as possible. HPTN 052 HAS NOT BEEN STOPPED!! Modifications are underway The Sponsor and investigators have decided to offer all infected subjects ART

8 HPTN 052 Prevention Results 39 total infections 28 linked infections 27 delayed arm 1 immediate arm o 17 of 27 infections in delayed arm occurred when the index partners CD4 was >350 7 unlinked infections 4 delayed arm 3 immediate arm p< infections still being analyzed (all in delayed arm)

9 CD4+ (cells/mm 3 ) HIV RNA (log 10 copies/mm 3 ) HIV Transmission, CD4 Count and HIV-1 RNA 28 Linked Transmissions Immediate (1) Delayed (27) Immediate (1) Delayed (27) Median proximal CD4 (range): 400 ( ) Immediate arm: 584 ( ) Delayed arm: 391 ( ) Median proximal log 10 VL (range): 4.9 ( ) Immediate arm: 2.6 ( ) Delayed arm: 4.9 ( )

10 HPTN 052 Clinical Results 105 morbidity and mortality events (trend, but did not meet pre-set criterion of >20% - p=0.07 however, when analyzed without pre set then p= 0.01) 65 in delayed arm 40 in immediate arm 20 cases of extrapulmonary TB (p= ) 17 in delayed arm 3 in immediate arm 23 deaths (NS) 13 in delayed arm 10 in immediate arm

11 Future Plans for HPTN 052 Offer ART to all study subjects in delay arm Continue study for at least 1 year: Continued durability of prevention benefit? Any differences in prevention benefit in those in delayed arm Clinical events and toxicity in both arms Adherence to ART

12 The Economist June 4, 2011

13 HPTN 052 IDEAS Couples Counseling is Important Unlinked Transmissions Matter Is there altruistic adherence? Why did we observe transmission in the ART arm? WHO Guidelines? Test and Treat?

14 WHAT DOES HPTN 052 MEAN? Why did we observe a transmission event in the ART arm? Did we observe greater adherence to ART than expected? Is there altruistic adherence? Test and Treat??

15 HPTN 052 Recognition U.S. Sponsors: National Institutes of Health (NIH) Division of AIDS (DAIDS), U.S. National Institute of Allergy and Infectious Diseases (NIAID) National Institute on Drug Abuse (NIDA) National Institute of Mental Health (NIMH) HIV Prevention Trials Network (HPTN): Network Laboratory, Johns Hopkins University Statistical Center for HIV/AIDS Research & Prevention (SCHARP) and University of Washington Coordinating and Operations Center, Family Health International (FHI) HPTN Leadership Pharmaceutical Companies: Abbott Laboratories Boehringer Ingelheim Pharmaceuticals, Inc. Bristol-Myers Squibb Gilead Sciences, Inc. GlaxoSmithKline Merck & Co., Inc. Sites (Investigators of Record): Porto Alegre, Brazil (Breno Santos) Rio de Janeiro, Brazil (Beatriz Grinsztejn) Boston, United States (Kenneth Mayer) Chennai, India (N. Kumarasamy) Pune, India (Sheela Godbole) Chiang Mai, Thailand (Suwat Chariyalertsak) Gaborone, Botswana (Joseph Makhema) Kisumu, Kenya (Lisa Mills) Blantyre, Malawi (Johnstone Kumwenda) Lilongwe, Malawi (Mina Hosseinipour) Johannesburg, South Africa (Ian Sanne) Soweto, South Africa (Guy De Bruyn) Harare, Zimbabwe (James Hakim) AIDS Clinical Trials Group (ACTG): ACTG Leadership and Investigators Study Participants