Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial

Family Health International, Durham, North Carolina, United States of America.
PLoS Clinical Trials (Impact Factor: 4.77). 05/2007; 2(5):e27. DOI: 10.1371/journal.pctr.0020027
Source: PubMed


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.
This was a phase 2, randomized, double-blind, placebo-controlled trial.
The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.
We enrolled 936 HIV-negative women at high risk of HIV infection into this study.
Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.
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.
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.
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.

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Available from: Anderson Sama Doh, Jul 16, 2014
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    • "There are several potential explanations for a lack of transgender enrollment in these trials. The relatively small size of transgender communities throughout the world – possibly 1 in 500 persons worldwide according to a 2007 estimate (Olyslager & Conway, 2007 "
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    ABSTRACT: Trans women are at high risk of HIV infection. We conducted a review to determine the extent to which trans women were eligible for inclusion in and enrolled into pre-exposure prophylaxis (PrEP) efficacy trials. Out of seven trials analyzing PrEP efficacy, we found that trans women comprised only 1.2% of one trial and 0.2% of total trial enrollments. Although an additional PrEP trial to determine efficacy among trans women may not be warranted, further research is needed to determine the effectiveness of PrEP in this marginalized population, through observational and feasibility studies. These studies should focus on unique barriers that trans women may experience while obtaining access to PrEP, such as gender discrimination, transphobia, and violence.
    AIDS Care 11/2014; 27(5):1-5. DOI:10.1080/09540121.2014.986051 · 1.60 Impact Factor
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    • "since it only included arms of factorial trials in which STI management was the only difference from the other trial arms (Figure 8) [25] [27] [32] [35] [64]. Figure 4 Male circumcision and the risk of HIV infection: evidence from controlled trials Citations to the included studies: Auvert 2005 [47], Bailey 2007 [48], Gray 2007 [49], Wawer 2009 [50], Weiss 2000 [51] Figure 5 Microbicides and the risk of HIV infection: evidence from controlled trials Citations to the included studies: Karim 2009 [52], Karim 2010 [53], McCormack 2010 [54], Skoler-karpoff 2008 [55], Peterson 2007 [46] Lassi et al. Reproductive Health 2014, 11(Suppl 3):S4 "
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    ABSTRACT: Infections can impact the reproductive health of women and hence may influence pregnancy related outcomes for both the mother and the child. These infections range from sexually transmitted infections (STIs) to TORCHS infections to periodontal disease to systemic infections and may be transmitted to the fetus during pregnancy, labor, delivery or breastfeeding. A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Preconception behavioral interventions significantly declines re-infection or new STI rates by 35% (95% CI: 20-47%). Further, condom use has been shown to be the most effective way to prevent HIV infection (85% protection in prospective studies) through sexual intercourse. Intervention trials showed that preconception vaccination against tetanus averted a significant number of neonatal deaths (including those specifically due to tetanus) when compared to placebo in women receiving more than 1 dose of the vaccine (OR 0.28; 95% CI: 0.15-0.52); (OR 0.02; 95% CI: 0.00-0.28) respectively. Preconception counseling should be offered to women of reproductive age as soon as they test HIV-positive, and conversely women of reproductive age should be screened with their partners before pregnancy. Risk assessment, screening, and treatment for specific infections should be a component of preconception care because there is convincing evidence that treatment of these infections before pregnancy prevents neonatal infections.
    Reproductive Health 09/2014; 11 Suppl 3(Suppl 3):S4. DOI:10.1186/1742-4755-11-S3-S4 · 1.88 Impact Factor
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    • "HIV-1 prevention studies enrolling women from sub-Saharan Africa have reported pregnancy incidence ranging from 3.95/100 person-years in the CAPRISA 004 trial of tenofovir vaginal gel in South Africa36 to 52/100 person-years in a phase 2 trial of oral tenofovir in West Africa.19 High pregnancy incidence in studies providing access to and counseling about contraception highlights the importance of HIV-1 prevention for women who may want to conceive with an infected or high-risk partner.39,40 "
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    ABSTRACT: Introduction: Pre-exposure prophylaxis (PrEP) may be an important safer conception strategy for HIV-1–uninfected women with HIV-1–infected partners. Understanding medication adherence in this population may inform whether PrEP is a feasible safer conception strategy. Methods: We evaluated predictors of pregnancy and adherence to study medication among HIV-1–uninfected women enrolled in a randomized placebo-controlled trial of PrEP among African HIV-1–serodiscordant couples. Participants were counseled on HIV-1 risk reduction, contraception, and adherence and tested for pregnancy at monthly study visits. Pill counts of dispensed drug were performed and, at a subset of visits, plasma was collected to measure active drug concentration. Results: Among 1785 women, pregnancy incidence was 10.2 per 100 person-years. Younger age, not using contraception, having an additional sexual partner, and reporting unprotected sex were associated with increased likelihood of pregnancy. Monthly clinic pill counts estimated that women experiencing pregnancy took 97% of prescribed doses overall, with at least 80% pill adherence for 98% of study months, and no difference in adherence in the periconception period compared with previous periods (P = 0.98). Tenofovir was detected in plasma at 71% of visits where pregnancy was discovered. By multiple measures, adherence was similar for women experiencing and not experiencing pregnancy (P ≥ 0.1). Conclusions: In this clinical trial of PrEP, pregnancy incidence was 10% per year despite excellent access to effective contraception. Women experiencing pregnancy had high medication adherence, suggesting that PrEP may be an acceptable and feasible safer conception strategy for HIV-1–uninfected women with HIV-1–serodiscordant partners.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2014; 67(1):91-97. DOI:10.1097/QAI.0000000000000246 · 4.56 Impact Factor
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