Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
Lancet HIV. 2017 Oct;4(10):e449-e456. doi: 10.1016/S2352-3018(17)30110-8. Epub 2017 Jul 18.
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.
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.
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=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=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; p=0·86).
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.
Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.
每日口服替诺福韦为基础的暴露前预防（PrEP）对高依从性的女性预防 HIV 非常有效。然而，异常阴道微生物群对 PrEP 疗效的影响令人关注。我们研究了细菌性阴道病是否改变了口服 PrEP 的疗效。
我们使用肯尼亚和乌干达艾滋病毒血清不一致夫妇中每日口服 PrEP（替诺福韦单药或替诺福韦和恩曲他滨联合治疗）的合作伙伴 PrEP 研究中前瞻性收集的数据，该研究为一项安慰剂对照试验，参与者为年龄在 18 岁或以上的女性，该研究表明 PrEP 对女性具有高度疗效。我们使用 Cox 比例风险回归评估根据每年显微镜检查和 Nugent 评分（0-3 表示健康微生物群，4-6 表示中间，7-10 表示细菌性阴道病）确定的细菌性阴道病状态的女性亚组中 PrEP 的疗效。在单独的疗效分析中，我们还研究了评分的个别组成部分（即，阴道加德纳菌或拟杆菌属的检测和乳酸杆菌属的未检测）作为异常微生物群的标志物。
在 1470 名女性（中位年龄 33 岁）中，357 名（24%）在入组时患有细菌性阴道病。45 名女性血清转换为 HIV。PrEP 对 HIV 的预防效果在具有健康微生物群的女性（PrEP 组的发病率为每 100 人年 0.6 例，安慰剂组为每 100 人年 2.5 例；疗效 76.55%[95%CI 43.09-90.37]）、中间微生物群（PrEP 组的发病率为每 100 人年 1.8 例，安慰剂组为每 100 人年 3.5 例；疗效 62.72%[95%CI -66.59-91.66]）或细菌性阴道病（PrEP 组的发病率为每 100 人年 0.9 例，安慰剂组为每 100 人年 3.5 例；疗效 72.50%[95%CI 5.98-91.95]）中没有显著差异；（p=0.871）。在检测到阴道加德纳菌或拟杆菌属形态和未检测到这些形态的女性之间（疗效 68.62% vs 76.72%；p=0.652），或在检测到乳酸杆菌属形态和未检测到这些形态的女性之间（疗效 70.48% vs 74.08%；p=0.86），PrEP 的疗效没有显著差异。
在细菌性阴道病流行率高且对 PrEP 高度依从的非洲女性中，每日口服 PrEP 对 HIV 的预防效果在异常阴道微生物群（根据 Nugent 评分定义）与健康阴道微生物群之间没有显著差异。这些数据令人放心，即可以继续向女性提供口服 PrEP 而无需同时检测细菌性阴道病或阴道菌群失调。
比尔和梅琳达·盖茨基金会、美国国立儿童健康与人类发展研究所和美国国立过敏和传染病研究所。
