Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study
Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study
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DOI：
10.1016/s2352-3018(17)30110-8
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发表时间：
2017-10-01
期刊：
影响因子：
16.1
通讯作者：
Baeten, Jared M.
中科院分区：
文献类型：
--
作者：
Heffron, Renee;McClelland, R. Scott;Baeten, Jared M.
背景以替诺福韦为基础的每日口服暴露前预防(PrEP)在高依从性的妇女中预防HIV是高效的。然而，异常的阴道微生物区系对PrEP疗效的影响值得关注。我们调查了细菌性阴道病是否改变了口服PrEP的疗效。方法我们使用了从合作伙伴PrEP研究中从女性那里收集的前瞻性数据，这是一项安慰剂对照试验，每天服用PrEP(替诺福韦单一治疗或替诺福韦和恩曲他滨联合治疗)在肯尼亚和乌干达18岁或18岁以上的HIV血清不一致夫妇中显示出对女性的高疗效。我们使用COX比例风险回归来评估根据细菌性阴道病状况定义的妇女亚组的PrEP疗效，这些亚组基于年度显微镜和Nugent评分(0-3代表健康微生物区系，4-6中度，7-10细菌性阴道病)。在单独的疗效分析中，我们还调查了评分的个别组成部分(即检测到阴道加德纳菌或类杆菌，没有检测到乳杆菌)作为异常微生物的标志。在1470名妇女(中位年龄33岁)中，357人(24%)在登记时患有细菌性阴道病。45名妇女血清转换为HIV。在具有健康微生物区系的妇女中，PrEP的艾滋病毒预防效果没有显著差异(PrEP组和安慰剂组分别为0.6/100人年和2.5/100人年；有效性为76.55%[95%可信区间43.09至90.37])，中等微生物群(PrEP组和安慰剂组分别为1.8/100人年和3.5/100人年；有效率为62.72%[95%可信区间为66.59~91.66]，或细菌性阴道病(艾滋病毒发病率：PREP组为0.9/百人年，安慰剂组为3.5/百人年；有效率为72.50%[95%可信区间为5.98~91.95]；P交互作用=0.871)。在检测到阴道革兰氏菌或类杆菌的妇女和那些没有这些形态的妇女之间，PREP的疗效没有显著差异(有效性68.62%比76.72%；P交互=0.652)；有乳杆菌属的妇女和没有这些形态的妇女之间(70.48%比74.08%；P交互=0.86.)。在细菌性阴道病的高患病率和对PrEP的高依从性的非洲妇女中，根据Nugent评分，每天口服PrEP预防艾滋病毒的有效性没有显著差异。这些数据令人放心，女性可以继续口服PrEP，而不需要同时检测细菌性阴道病或阴道失调。基金会由比尔和梅琳达·盖茨基金会、尤妮斯·肯尼迪·施莱弗国家儿童健康和人类发育研究所以及国家过敏和传染病研究所提供。
Background Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP.Methods We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0-3 indicated healthy microbiota, 4-6 intermediate, and 7-10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota.Findings Of 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0.6 per 100 person years in PrEP group and 2.5 per 100 person-years in the placebo group; efficacy 76.55% [95% CI 43.09 to 90.37]), intermediate microbiota (HIV incidence 1.8 per 100 person-years in the PrEP group and 3.5 per 100 person-years in the placebo group; efficacy 62.72% [95% CI-66.59 to 91.66]), or bacterial vaginosis (HIV incidence 0.9 per 100 person-years in the PrEP group and 3.5 per 100 person-years in the placebo group; efficacy 72.50% [95% CI 5.98 to 91.95]; P-interaction=0.871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68.62% vs 76.72%; P-interaction=0.652); or between those with Lactobacillus spp morphotypes and those without (70.48% vs 74.08%; P-interaction=0.86).Interpretation Among African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis.Funding Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.