title: Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  The objective of this trial was to investigate the safety and preliminary effectiveness of a daily dose of 300 mg of tenofovir disoproxil fumarate (TDF) versus placebo in preventing HIV infection in women.
  
  
  METHODS
  This was a phase 2, randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.
  
  
  METHODS
  We enrolled 936 HIV-negative women at high risk of HIV infection into this study.
  
  
  METHODS
  Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.
  
  
  METHODS
  The primary safety endpoints were grade 2 or higher serum creatinine elevations (>2.0 mg/dl) for renal function, grade 3 or 4 aspartate aminotransferase or alanine aminotransferase elevations (>170 U/l) for hepatic function, and grade 3 or 4 phosphorus abnormalities (<1.5 mg/dl). The effectiveness endpoint was infection with HIV-1 or HIV-2.
  
  
  RESULTS
  Study participants contributed 428 person-years of laboratory testing to the primary safety analysis. No significant differences emerged between treatment groups in clinical or laboratory safety outcomes. Study participants contributed 476 person-years of HIV testing to the primary effectiveness analysis, during which time eight seroconversions occurred. Two were diagnosed in participants randomized to TDF (0.86 per 100 person-years) and six in participants receiving placebo (2.48 per 100 person-years), yielding a rate ratio of 0.35 (95% confidence interval = 0.03-1.93), which did not achieve statistical significance. Owing to premature closures of the Cameroon and Nigeria study sites, the planned person-years of follow-up and study power could not be achieved.
  
  
  CONCLUSIONS
  Daily oral use of TDF in HIV-uninfected women was not associated with increased clinical or laboratory adverse events. Effectiveness could not be conclusively evaluated because of the small number of HIV infections observed during the study.
authors.affiliation: Family Health International, Durham, North Carolina, United States of America. lpeterson@fhi.org
authors.forename: Leigh
authors.initials: L
authors.lastname: Peterson
authors.forename: Doug
authors.initials: D
authors.lastname: Taylor
authors.forename: Ronald
authors.initials: R
authors.lastname: Roddy
authors.forename: Ghiorghis
authors.initials: G
authors.lastname: Belai
authors.forename: Pamela
authors.initials: P
authors.lastname: Phillips
authors.forename: Kavita
authors.initials: K
authors.lastname: Nanda
authors.forename: Robert
authors.initials: R
authors.lastname: Grant
authors.forename: Edith Essie Kekawo
authors.initials: EE
authors.lastname: Clarke
authors.forename: Anderson Sama
authors.initials: AS
authors.lastname: Doh
authors.forename: Renee
authors.initials: R
authors.lastname: Ridzon
authors.forename: Howard S
authors.initials: HS
authors.lastname: Jaffe
authors.forename: Willard
authors.initials: W
authors.lastname: Cates