It has been well-documented that combination antiretroviral therapy can lower HIV viral load and delay HIV disease progression to AIDS. Seronegative sexual partners of seropositive persons are especially at risk for HIV infection; epidemiological studies suggest that treatment with antiretrovirals can decrease sexual transmission in these discordant couples. The timing of antiretroviral administration to those infected with HIV has however been controversial. It is unclear whether immediate therapy, at the time of diagnosis, or delayed therapy, at the time of low CD4 T cell counts, would better prevent acquisition.
HPTN investigators, including VIDD members Dr. Ying Chen and Dr. Thomas Fleming and VIDD senior staff scientist Dr. Lei Wang, designed and implemented a long-term, large-scale, randomized controlled Phase III study to compare prevention of HIV transmission and development of HIV-related illness in serodiscordant couples after administration of antiretrovirals immediately after HIV diagnosis (early) and at the time of low CD4 T cell counts (delayed). This study, which was started to enroll eligible discordant couples as early as in 2005, randomly assigned early or delayed therapy to over 1700 HIV positive partners of serodiscordant couples and was planned to follow up every enrolled couple for at least 60 months. For the first planned interim analysis using data collected as of February 21, 2011, 28 genetically-linked HIV transmission events were observed: 1 event in the early therapy group and 27 in the delayed group, showing that early therapy reduced HIV transmission by 96 percent as compared to delayed therapy. The researchers also found that early treatment reduced HIV-related deaths and severe side effects of the infection, such as extrapulmonary tuberculosis, in the HIV positive partners. This study is the first randomized controlled clinical trial to show that early antiretroviral therapy results in a considerable reduction in the risk of HIV transmission between serodiscordant couples and progression to late-stage disease.
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505