title: Tenofovir-based preexposure prophylaxis for HIV infection among African women.
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.).
authors: 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).
authors: Jeanne M
authors: JM
authors: Marrazzo
authors: Gita
authors: G
authors: Ramjee
authors: Barbra A
authors: BA
authors: Richardson
authors: Kailazarid
authors: K
authors: Gomez
authors: Nyaradzo
authors: N
authors: Mgodi
authors: Gonasagrie
authors: G
authors: Nair
authors: Thesla
authors: T
authors: Palanee
authors: Clemensia
authors: C
authors: Nakabiito
authors: Ariane
authors: A
authors: van der Straten
authors: Lisa
authors: L
authors: Noguchi
authors: Craig W
authors: CW
authors: Hendrix
authors: James Y
authors: JY
authors: Dai
authors: Shayhana
authors: S
authors: Ganesh
authors: Baningi
authors: B
authors: Mkhize
authors: Marthinette
authors: M
authors: Taljaard
authors: Urvi M
authors: UM
authors: Parikh
authors: Jeanna
authors: J
authors: Piper
authors: Benoît
authors: B
authors: Mâsse
authors: Cynthia
authors: C
authors: Grossman
authors: James
authors: J
authors: Rooney
authors: Jill L
authors: JL
authors: Schwartz
authors: Heather
authors: H
authors: Watts
authors: Mark A
authors: MA
authors: Marzinke
authors: Sharon L
authors: SL
authors: Hillier
authors: Ian M
authors: IM
authors: McGowan
authors: Z Mike
authors: ZM
authors: Chirenje
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D000282:Administration, Intravaginal; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000517:prevention & control*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D055118:Medication Adherence; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D065129:Pre-Exposure Prophylaxis; D011795:Surveys and Questionnaires; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
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