Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women.
Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women.
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DOI：
10.1016/s0140-6736(11)60878-7
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发表时间：
2011-07-16
期刊：
影响因子：
168.9
通讯作者：
Karim, Quarraisha Abdool
中科院分区：
文献类型：
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作者：
Karim, Salim S. Abdool;Kashuba, Angela D. M.;Werner, Lise;Karim, Quarraisha Abdool
评估口服抗逆转录病毒药物暴露前预防轴（PrEP）在女性中的有效性的临床试验FEM-PrEP，1的早期关闭是艾滋病毒预防的重大挫折。鉴于暴露前预防倡议（iPrEX）试验2和艾滋病研究计划中心的良好结果，对这项试验的期望很高南非（CAPRISA 004）试验3在异性恋女性中测试了替诺福韦凝胶（一种外用PrEP制剂）。因此，2011年4月18日宣布的FEM-PrEP试验结果显示，对艾滋病毒感染没有保护作用，令人失望。利用公开信息1和来自其他PrEP研究的数据，我们为FEM-PrEP试验的结果提供了一个潜在的解释。在艾滋病毒高流行率环境中，如撒哈拉以南非洲，年轻女性的艾滋病毒发病率不成比例地高，比同龄男性高出8倍。4现有的艾滋病毒预防战略为感染风险高但无法说服其伴侣忠诚或使用避孕套的年轻妇女提供的选择很少，这突出表明迫切需要由妇女发起的艾滋病毒预防技术。为此，在过去17年中进行了几次杀微生物剂试验。直到2010年，没有一个国家显示出对艾滋病毒感染的保护。5.需要采取新的办法。抗逆转录病毒药物已经证明在治疗艾滋病毒感染和预防母婴传播方面是有效的，它预示着预防性传播的一种新选择。FEM-PrEP是一项III期、双盲、随机、安慰剂对照试验，评估每日口服富马酸替诺福韦酯和恩曲他滨预防南非、肯尼亚和坦桑尼亚18-35岁女性感染艾滋病毒的有效性。在预定的中期分析中，1951名入组妇女的HIV发病率为5/100人-年，56个HIV终点在研究组之间平均分布。1继续研究至计划的72个HIV终点以显示有效性被认为是徒劳的，因此决定有序关闭试验。为什么FEM-PrEP试验没有显示出对HIV感染的保护作用？得出口服替诺福韦酯和恩曲他滨不能预防女性HIV感染的结论过于简单和过早;试验中报告的主要HIV结局存在几种可能的解释。这样的结果
The early closure of a clinical trial assessing the effective ness of oral antiretroviral pre-exposure pro phyl axis (PrEP) in women, FEM-PrEP, 1 is a substantial setback for HIV prevention. Expectations of this trial were high in view of favourable results from the pre-exposure prophylaxis initiative (iPrEX) trial, 2 which studied the same drug and dosing strategy in men who have sex with men, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA 004) trial, 3 which tested tenofovir gel (a topical PrEP formulation) in heterosexual women. As a result, the interim FEM-PrEP trial results, announced on April 18, 2011, which showed no protection against HIV infection, 1 were disappointing. Using publicly available information1 and data from other PrEP studies, we offer a potential explanation for the results of the FEM-PrEP trial.In high HIV prevalence settings, such as sub-Saharan Africa, young women have disproportionately high HIV incidence rates, up to 8-times higher than for men of the same age. 4 Available HIV prevention strategies provide few options for young women who are at high risk of infection but who are unable to convince their partner to be faithful or use condoms, underscoring the urgent need for a women-initiated HIV prevention technology. To this end, several microbicide trials have been undertaken during the past 17 years. Until 2010, none had shown protection against HIV acquisition. 5 A new approach was needed. Antiretroviral drugs, already shown to be effective in treating HIV infection and prevention of mother-to-child transmission, heralded a new option to prevent sexual transmission. FEM-PrEP was a phase 3, double-blind, randomised, placebo-controlled trial assessing the effectiveness of daily oral tenofovir disoproxil fumarate and emtricitabine for prevention of HIV acquisition in women aged 18–35 years in South Africa, Kenya, and Tanzania. At a scheduled interim analysis, the HIV incidence rate was 5 per 100 person-years in the 1951 women enrolled, and the 56 HIV endpoints were equally distributed between the study groups. 1 Continuation of the study to the planned 72 HIV endpoints in an attempt to show effectiveness was deemed futile, so the decision was made to undertake an orderly closure of the trial. Why did the FEM-PrEP trial not show protection against HIV infection? To conclude that oral tenofovir disoproxil fumarate and emtricitabine does not prevent HIV infection in women would be overly simplistic and premature; several possible explanations exist for the reported primary HIV outcome in the trial. Such results