Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial.
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.
Peterson
Leigh
L
Family Health International, Durham, North Carolina, United States of America. lpeterson@fhi.org
Taylor
Doug
D
Roddy
Ronald
R
Belai
Ghiorghis
G
Phillips
Pamela
P
Nanda
Kavita
K
Grant
Robert
R
Clarke
Edith Essie Kekawo
EE
Doh
Anderson Sama
AS
Ridzon
Renee
R
Jaffe
Howard S
HS
Cates
Willard
W