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N Engl J Med. 2015 Feb 5;372(6):509-18. doi: 10.1056/NEJMoa1402269.

Tenofovir-based preexposure prophylaxis for HIV infection among African women.

Author information

1
From the University of Washington (J.M.M.) and the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center (B.A.R., J.Y.D., B. Mâsse) - both in Seattle; the HIV Prevention Research Unit, Medical Research Council (G.R., S.G.), and the Centre for AIDS Programme of Research in South Africa (CAPRISA), Durban (G.N.), Witwatersrand Reproductive Health and HIV Research Institute (T.P.) and Perinatal HIV Research Unit (B. Mkhize), Johannesburg, and the AURUM Institute, Klerksdorp (M.T.) - all in South Africa; FHI 360, Durham, NC (K.G.); University of Zimbabwe-University of California San Francisco Research Programme, Harare, Zimbabwe (N.M., Z.M.C.); Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda (C.N.); Women's Global Health Imperative, Research Triangle Institute (RTI) International, San Francisco (A.S.); Magee-Womens Research Institute, University of Pittsburgh Medical Center, Pittsburgh (L.N., U.M.P., S.L.H., I.M.M.); Johns Hopkins University School of Medicine, Baltimore (C.W.H., M.A.M.); Division of AIDS, National Institute of Allergy and Infectious Diseases (J.P.), National Institutes of Mental Health (C.G.), and the Eunice Shriver Kennedy National Institute of Child Health and Human Development (H.W.), National Institutes of Health - all in Bethesda, MD; Gilead Sciences, Foster City, CA (J.R.); CONRAD, Arlington, VA (J.L.S.); and Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal (B. Mâsse).

Abstract

BACKGROUND:

Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.

METHODS:

We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly.

RESULTS:

Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events.

CONCLUSIONS:

None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).

PMID:
25651245
PMCID:
PMC4341965
DOI:
10.1056/NEJMoa1402269
[Indexed for MEDLINE]
Free PMC Article

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