Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women

Bibliographic Data

ID23380063
AuthorsJared M Baeten (0000-0001-8242-8438, University of Washington), Deborah Donnell (0000-0002-0587-7480, University of Washington), Patrick Ndase, Nelly Mugo (0000-0002-2347-006X, University of Nairobi), Nelly R Mugo, John D Campbell (0000-0002-2931-9643, Centers for Disease Control and Prevention), James D Campbell (0000-0001-7117-5121), Jonathan Wangisi (The AIDS Support Organization), Jordan W Tappero (0000-0001-5538-2067), Elizabeth A Bukusi (0000-0002-2031-2808, University of Nairobi), Craig R Cohen (0000-0001-8654-6634, University of California, San Francisco), Elly Katabira (0000-0001-9951-755X, Makerere University), Allan Ronald (0000-0002-5746-3490, University of Manitoba), Elioda Tumwesigye, Edwin Were (0000-0002-4783-0795, Moi University), Kenneth H Fife (Indiana University – Purdue University Indianapolis), James Kiarie (0000-0003-4180-7858, University of Nairobi), Carey Farquhar (0000-0001-8575-3439), Grace John-Stewart, Grace John‐Stewart (0000-0002-4301-1573), Aloysious Kakia (0000-0003-2549-8864, The AIDS Support Organization), Josephine Odoyo (0000-0003-1749-8645, Kenya Medical Research Institute), Akasiima Mucunguzi (0000-0003-3601-6744, The AIDS Support Organization), Moses Joloba (0000-0002-0334-9983, Makerere University), Edith Nakku-Joloba (0000-0002-2188-1877), Rogers Twesigye, Kenneth Ngure (0000-0002-8062-0933, University of Nairobi), Cosmas Apaka (Moi University), Harrison Tamooh, Fridah Gabona (Makerere University), Andrew Mujugira (0000-0001-6646-6733), Dana Panteleeff, Katherine K Thomas (0000-0002-7024-468X), Lara Kidoguchi, Meighan Krows (0000-0003-0321-9203), Jennifer Revall, Susan Morrison (0009-0000-8826-8076), Harald Haugen, Harald S Haugen (0000-0002-2034-2150), Mira Emmanuel-Ogier, Lisa Ondrejcek, Robert W Coombs (0000-0003-2709-0512), Lisa M Frenkel (0000-0001-9566-8959, Seattle Children's Hospital), Lisa Frenkel, Craig W Hendrix (0000-0002-5696-8665, Johns Hopkins University), Craig Hendrix, Namandjé N Bumpus (0000-0002-6096-3824, National Clinical Research), David R Bangsberg (0000-0002-6352-8908, Harvard University), David Bangsberg, Jessica E Haberer (0000-0001-5845-3190, Harvard University), Wendy Stevens (0000-0002-1684-908X, National Clinical Research), Wendy S Stevens, Jairam R Lingappa (0000-0001-6191-9828, Pediatrics and Genetics), Connie Celum (0000-0002-8813-3419)
Year2012
Volume367
Issue5
Pages399-410
Publication date2012-08-02
Peer ReviewedYes
Open AccessNo
TypeARTICLE
VenueNew England Journal of Medicine (JOURNAL)
Journal identifiersISSN: 0028-4793 • E-ISSN: 1533-4406
PublisherMassachusetts Medical Society (PUBLISHER • US)
DOI10.1056/nejmoa1108524
PMID22784037
PMCIDPMC3770474
OpenAlexW2117057469
LanguageEN
Citations received516
References cited35

BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).

Antiretroviral therapy · Confidence interval · Emtricitabine · Human immunodeficiency virus (HIV) · Incidence (geometry) · Interquartile range · Men who have sex with men · Placebo · Pre-exposure prophylaxis · Randomized controlled trial · Serodiscordant · Syphilis · Viral load · HIV Research and Treatment · HIV/AIDS drug development and treatment · HIV/AIDS Research and Interventions · Immunology · Internal Medicine · Medicine