Prevention of HIV-1 infection with early antiretroviral therapy

Myron S. Cohen, Ying Q. Chen, Marybeth McCauley, Theresa Gamble, Mina C. Hosseinipour, Nagalingeswaran Kumarasamy, James G. Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose H S Pilotto, Sheela V. Godbole, Sanjay Mehendale, Suwat Chariyalertsak, Breno R. Santos, Kenneth H. Mayer, Irving F. Hoffman, Susan H. Eshleman, Estelle Piwowar-Manning, Lei Wang, Joseph MakhemaLisa A. Mills, Guy De Bruyn, Ian Sanne, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Heather Ribaudo, Vanessa Elharrar, David Burns, Taha E. Taha, Karin Nielsen-Saines, David Celentano, Max Essex, Thomas R. Fleming

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Abstract

BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the earlytherapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.)

Original languageEnglish (US)
Pages (from-to)493-505
Number of pages13
JournalNew England Journal of Medicine
Volume365
Issue number6
DOIs
StatePublished - Aug 11 2011

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ASJC Scopus subject areas

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Cohen, M. S., Chen, Y. Q., McCauley, M., Gamble, T., Hosseinipour, M. C., Kumarasamy, N., Hakim, J. G., Kumwenda, J., Grinsztejn, B., Pilotto, J. H. S., Godbole, S. V., Mehendale, S., Chariyalertsak, S., Santos, B. R., Mayer, K. H., Hoffman, I. F., Eshleman, S. H., Piwowar-Manning, E., Wang, L., ... Fleming, T. R. (2011). Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine, 365(6), 493-505. https://doi.org/10.1056/NEJMoa1105243