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Abstract
Findings from a double-blind, randomized, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) for prevention of HIV infection in women
L. Peterson1, D. Taylor1, E.E.K. Clarke2, A.S. Doh3, P. Phillips1, G. Belai1, K. Nanda1, R. Ridzon4, H.S. Jaffe5, W. Cates1
1Family Health International, Durham, North Carolina, United States, 2Ministry of Health, Accra, Ghana, 3University of Yaoundé, Yaoundé, Cameroon, 4Bill & Melinda Gates Foundation, Seattle, Washington, United States, 5Gilead Sciences, Inc., Foster City, California, United States
Background: Animal studies have suggested that TDF may be effective for prophylaxis against HIV infection. We investigated the safety and preliminary prophylactic effectiveness of a daily dose of 300 mg TDF versus placebo in HIV-uninfected women.
Methods: Between June 2004 and March 2005, we enrolled 936 HIV-negative women into a double-blind, randomized trial (1:1 TDF:placebo) in Ghana, Cameroon, and Nigeria. Participants made up to 12 monthly visits for study drug re-supply, HIV testing and adverse event (AE) reporting. Laboratory testing (serum creatinine, phosphorus, ALT, and AST) was done quarterly, and ALT/AST levels were monitored in a subset of participants after study drug was withdrawn. Analysis of laboratory abnormalities was restricted to data from Ghana and Cameroon.
Results: The most common AEs were malaria, candidiasis, headache, abdominal pain, and dizziness, with no significant differences between treatment groups. Furthermore, no significant differences emerged between groups for Grade 3 or higher laboratory abnormalities. Specifically, none of the 363 participants in the TDF group had ALT or AST elevations greater than 170 U/L prior to product withdrawal, and 2/368 and 3/368 of the participants in the placebo group had elevated (>170 U/L) ALT and AST levels, respectively. Two participants in the TDF group and one in the placebo group had decreases in phosphorus to less than 1.5 mg/dL. One participant in the placebo group had a creatinine elevation greater than 3.0 mg/dL. Two HIV infections were diagnosed in participants randomized to TDF (rate = 0.86 per 100 person-years) and six in participants receiving placebo (rate = 2.48 per 100 person-years), yielding a rate ratio of 0.35 (95% confidence interval = 0.03-1.93).
Conclusions: TDF did not increase the rate of adverse events or Grade 3-4 laboratory abnormalities in participants during or after use. The number of HIV infections was insufficient to conclude that TDF protected against HIV infection.
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