Leigh Peterson, Doug Taylor, Ronald Roddy, Ghiorghis Belai, Pamela Phillips, Kavita Nanda, Robert Grant, Edith Essie Kekawo Clarke, Anderson Sama Doh, Renee Ridzon, Howard S Jaffe, Willard Cates
{"title":"Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial.","authors":"Leigh Peterson, Doug Taylor, Ronald Roddy, Ghiorghis Belai, Pamela Phillips, Kavita Nanda, Robert Grant, Edith Essie Kekawo Clarke, Anderson Sama Doh, Renee Ridzon, Howard S Jaffe, Willard Cates","doi":"10.1371/journal.pctr.0020027","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>This was a phase 2, randomized, double-blind, placebo-controlled trial.</p><p><strong>Setting: </strong>The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.</p><p><strong>Participants: </strong>We enrolled 936 HIV-negative women at high risk of HIV infection into this study.</p><p><strong>Intervention: </strong>Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.</p><p><strong>Outcome measures: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2007-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0020027","citationCount":"281","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS clinical trials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1371/journal.pctr.0020027","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 281
Abstract
Objectives: 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.
Design: This was a phase 2, randomized, double-blind, placebo-controlled trial.
Setting: The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.
Participants: We enrolled 936 HIV-negative women at high risk of HIV infection into this study.
Intervention: Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.
Outcome measures: 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.
Conclusion: 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.