1 / 22

Myron S. Cohen, MD Protocol Chair 6 th IAS Conference, Rome, Italy July 18, 2011

Myron S. Cohen, MD Protocol Chair 6 th IAS Conference, Rome, Italy July 18, 2011. HPTN 052. Antiviral Treatment as Prevention. Extensive biological plausibility The concentration of HIV-1 in blood and genital tract correlates with sexual transmission

zwi
Download Presentation

Myron S. Cohen, MD Protocol Chair 6 th IAS Conference, Rome, Italy July 18, 2011

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Myron S. Cohen, MDProtocol Chair6th IAS Conference, Rome, ItalyJuly 18, 2011 HPTN 052

  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 viral load Most observational reports indicate ART reduces transmission of HIV-1 in couples

  3. To determine if ART reduces HIV-1 transmission magnitude? durability of benefit? To determine if ART is used “earlier” to reduce HIV-1 transmission personal health benefit(s)? ARandomized Controlled Trial

  4. HIV Prevention: RCT (Cohen) Linkage Analysis (Eshleman) HIV-1 Virology and Immunology (Hosseinipour) When to Start ART (Grinsztejn) Summary (Cohen) Questions and Answers HPTN 052 Presentations

  5. Prevention of Transmission of HIV with ART M Cohen, Y Chen, M McCauley, T Gamble, R Bollinger, Y Bryson, D Burns, D Celentano, S Chariyalertsak,F Conradie, L Cottle, G De Bruyn, V Elharrar, S Eshleman, M Essex, E Filho, S Godbole, B Grinsztejn, J Hakim,I Hoffman, M Hosseinipour, N Kumarasamy, J Kumwenda, J Makhema, A Martinez, K Mayer, S Mehendale, L Mills, K Nielsen, J Pilotto, E Piwowar-Manning, I Sanne, B Santos, T Taha, L Wang, S Safren, T Fleming,and the HPTN 052 Protocol Team

  6. HPTN 052 Study Design Stable, healthy, serodiscordant couples, sexually active CD4 count: 350 to 550 cells/mm3 Randomization Immediate ART CD4 350-550 Delayed ART CD4 <250 Primary Transmission Endpoint Virologically-linked transmission events Primary Clinical Endpoint WHO stage 4 clinical events, pulmonary tuberculosis, severe bacterial infection and/or death

  7. HPTN 052 Enrollment 10,838 Individuals Screened Major reasons for exclusion: 3058 HIV+ but CD4 count out of range 2565 HIV- but HIV+ partner ineligible 308 Seroconcordant couples 155 Ineligible due to sexual history 1763 Couples (3526 Individuals) Randomized Immediate Arm 886 Couples Delayed Arm 877 Couples

  8. HPTN 052 Enrollment (Total Enrollment: 1763 couples) U.S. Thailand India Americas 278 Kenya Malawi Asia 531 Brazil Zimbabwe Botswana South Africa Africa 954

  9. HPTN 052 Enrollment

  10. HPTN 052: Baseline Characteristics

  11. HPTN 052: Baseline Characteristics

  12. “The Board recommends that the results of the trial be announced as soon as possible” HPTN 052 continues to follow couples, but all HIV-infected participants are being offered ART DSMB Recommendation April 28, 2011

  13. HPTN 052: HIV-1 Transmission Total HIV-1 Transmission Events: 39 Immediate Arm 4 Delayed Arm 35 p < 0.0001

  14. HPTN 052: HIV-1 Transmission Total HIV-1 Transmission Events: 39 Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 • 18/28 (64%) transmissions from infected participants with CD4 >350 cells/mm3 • 23/28 (82%) transmissions in sub-Saharan Africa • 18/28 (64%) transmissions from female to male partners Immediate Arm: 1 Delayed Arm: 27 p < 0.001

  15. Median follow-up: 1.7 years HPTN 052: HIV-1 Transmission *Person-years specific for transmission events

  16. HPTN052: HIV-1 Transmissions

  17. Sexual Behaviors: Baseline and Follow-up • *STDs include hepatitis B, syphilis, gonorrhea, and C. trachomatis • **Self-reported data

  18. HPTN 052: Effect of ART Proportion of participants with VL<400 at each visit 100 Immediate Arm Delayed Arm (not on ART) Delayed Arm (on ART) 80 60 40 20 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Months

  19. HIV Transmission: CD4 Count and HIV-1 RNA 28 Linked Transmissions HIV RNA (log10 copies/mm3) CD4+ (cells/mm3) Immediate (1) Delayed (27) Immediate (1) Delayed (27) • Median proximal CD4 (range): 400 (229-858) • Immediate arm: 584 (584-584) • Delayed arm: 391 (229-858) • Median proximal log10 VL (range): 4.9 (2.6-5.8) • Immediate arm: 2.6 (2.6-2.6) • Delayed arm: 4.9 (2.6-5.8)

  20. One Transmission Event on ART Index begins ART AZT/3TC/EFV Index VL<400 Partner HIV+ (WB) Enrollment Screening -14 0 1 Days 28 85 Partner VL < 400 Index CD4 = 482 Index VL = 87,202 • Single Genome Analysis: 1-2 viruses transmitted • Analysis of Transmission: >50 days earlier (84 – 190 days)

  21. Multivariate Analysis – Linked Transmission

  22. HPTN 052 Prevention Conclusion Early ART that suppresses viral replication led to 96% reduction of sexual transmission of HIV-1 in serodiscordant couples THANK YOU!

More Related