Antiretroviral therapy to prevent the sexual transmission of HIV-1 and reduce HIV-1 associated morbidity and mortality: baseline data from HPTN 052
N. Kumarasamy1, M. Hosseinipour2, J. Kumwenda3, J. Hakim4, B. Grinsztejn5, J. Pilotto6, S. Godbole7, S. Chariyalertsak8, B. Santos9, I. Sanne10, J. Makhema11, G. de Bruyn12, L. Mills13, E. Filho14, K. Mayer15, M. McCauley16, T. Gamble17, E. Piwowar-Manning18, Y. Chen19, D. Havlir20, M. Cohen21, HPTN 052 Protocol Team
1YRG CARE, Chennai, India, 2UNC Project, Lilongwe, Malawi, 3College of Medicine - Johns Hopkins University Research Project, Blantyre, Malawi, 4University of Zimbabwe - UZ-UCSF CTU-Parirenyatwa CRS, Harare, Zimbabwe, 5Instituto de Pesquisa Clínica Evandro Chagas, Rio de Janeiro, Brazil, 6Hospital Geral De Nova Iguaçu, Rio de Janeiro, Brazil, 7National AIDS Research Institute, Pune, India, 8Research Institute for Health Sciences, Chiang Mai, Thailand, 9Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, 10Witwatersrand Clinical Research Site, Johannesburg, South Africa, 11Gaborone Prevention/Treatment Trials CRS, Gaborone, Botswana, 12Soweto HPTN CRS, Soweto, South Africa, 13KEMRI/CDC, Kisumu, Kenya, 14Hospital dos Servidores do Estado, Rio de Janeiro, Brazil, 15Fenway Community Health Center, Boston, United States, 16Family Health International, Arlington, United States, 17Family Health International, Durham, United States, 18Johns Hopkins University, Baltimore, United States, 19Fred Hutchinson Cancer Research Center, Seattle, United States, 20University of California, San Francisco, United States, 21The University of North Carolina at Chapel Hill, Chapel Hill, United States
Background: Observational data show that antiretroviral therapy (ART) greatly reduces the sexual transmission of HIV-1, suggesting that ART may play an important role in prevention. Recent observational data suggest that ART initiated earlier reduces HIV-1 associated complications, and the WHO recently recommended initiation of ART at higher CD4+ levels. HPTN 052 is a randomized trial to determine whether ART offered at higher CD4+ cell counts (350-550 cells/mm3) prevents sexual transmission of HIV-1 and reduces HIV-1 associated morbidity and mortality.
Methods: This an ongoing, prospective, two-arm, randomized, multicenter study of 1750 HIV-1 infected individuals (index case) and their HIV-negative sexual partners (partner). Each enrolled couple will be followed for at least 5 years. Index cases are randomized for ART initiation at enrollment or when their CD4+ cell count falls below 250 cells/mm3. Study endpoints include HIV seroconversion of the partner and time to WHO stage 4 event, pulmonary tuberculosis, severe bacterial infection or death for the index case.
Results: The study began in June 2005 and has now completed enrollment of 1750 couples worldwide. To date, index cases and their partners have accrued 1596 and 1494 person-years of follow-up, respectively. The current 12-month retention rate is 96% for index cases and 91% for partners. The median baseline CD4+ cell count is 433 cells/mm3 (min-max = 105 - 1311) and the median baseline HIV RNA (log10 scale) is 4.4 (min-max = 2.4 - 6.7). At baseline, the majority of patients (94% index; 96% partner) report having only 1 sexual partner, and most report having had sex in the last week.
Conclusions: HPTN 052 has successfully recruited a very large cohort of HIV‑1 serodiscordant couples in the first randomized trial to determine whether the use of ART can prevent the sexual transmission of HIV-1 and to quantify the clinical effects of starting early initiation of ART.
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