Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
Department of Epidemiology, Columbia University, New York, New York, USA.
Curr Opin HIV AIDS. 2018 Jan;13(1):81-87. doi: 10.1097/COH.0000000000000431.
HIV prevention approaches that women can use and control are a priority. Results from topical and oral preexposure prophylaxis (PrEP) HIV prevention trials have produced inconsistent results in women. One of the main behavioural factors impacting effectiveness of PrEP has been suboptimal adherence. In this review, we examine biological factors that modulate topical PrEP efficacy, with particular focus on the vaginal microbiome.
Genital inflammation is an independent risk factor for HIV acquisition in women. Using 16S rRNA sequencing of the vaginal microbiota, anaerobic bacteria linked with bacterial vaginosis have been shown to be associated with both genital inflammation and HIV risk. Using proteomics, it was recently discovered that a dysbiotic vaginal microbiome, comprising less than 50% Lactobacillus spp., directly influenced topical PrEP efficacy. Gardnerella vaginalis, the dominant vaginal species in dysbiotic women, was able to directly degrade tenofovir, but not dapivirine, an antiretroviral also being developed for topical PrEP.
The link between bacterial vaginosis-associated organisms with HIV risk and altered tenofovir gel effectiveness underscores the importance of good vaginal health and good adherence for women to benefit maximally from topical PrEP. Altering the vaginal microbiome is one of the new directions being pursued for HIV prevention.
目的综述：女性可使用和控制的艾滋病预防方法是重中之重。局部和口服暴露前预防（PrEP）艾滋病预防试验的结果在女性中产生了不一致的结果。影响 PrEP 效果的主要行为因素之一是用药依从性差。在这篇综述中，我们研究了调节局部 PrEP 疗效的生物学因素，特别关注阴道微生物组。
最新发现：生殖器炎症是女性获得性艾滋病的一个独立危险因素。使用阴道微生物组的 16S rRNA 测序，与细菌性阴道病相关的厌氧菌已被证明与生殖器炎症和 HIV 风险都有关。最近通过蛋白质组学发现，一种由少于 50%的乳杆菌属组成的失调阴道微生物组，直接影响局部 PrEP 的疗效。在失调的女性中占主导地位的阴道物种加德纳菌能够直接降解替诺福韦，但不能降解也在开发用于局部 PrEP 的抗逆转录病毒药物双夫定。
总结：细菌性阴道病相关病原体与 HIV 风险之间的联系以及改变替诺福韦凝胶有效性，突显了良好的阴道健康和良好的用药依从性对女性从局部 PrEP 中最大程度获益的重要性。改变阴道微生物组是预防艾滋病的新方向之一。
