Mechanisms underlying recurrent bacterial vaginosis and HIV risk A Multidisciplinary approach

摘要 细菌性阴道病(BV)是影响女性生殖道的最常见的健康状况， 极大地增加了妇女感染艾滋病毒和性传播感染的风险。BV的特点是 阴道细菌的组成(微生物区系)，减少健康的阴道乳杆菌种类和 革兰氏阴性厌氧菌增多。患有BV的女性女性生殖道受损 粘膜免疫反应与HIV靶细胞的增加以及上皮完整性的降低；所有这些 导致艾滋病毒风险增加。此外，最近的一项研究表明，BV相关细菌可以直接 使用于预防艾滋病毒的药物水解化，造成破坏治疗效果的条件。当前 在大多数女性中，以抗生素为基础的BV治疗会导致治疗失败或复发。 行为(性行为和阴道内卫生做法，如阴道内冲洗)，细菌 因素(微生物组和病毒组)和宿主生物因素(粘膜免疫反应和炎症)， 所有这些都可能强调BV的复发。在这项研究中，我们将评估BV复发的机制。 患有BV的育龄妇女(18-45岁)的独特队列。患有BV的育龄妇女将是 提供BV治疗，并进行纵向随访(BV治疗后1个月和6个月)。研究目标为：1) 评价阴道内卫生措施在预防BV复发中的作用；2)评价阴道的作用 微生物群和病毒体，以及阴道细菌对抗生素的代谢，对BV复发的影响；3)评估 宿主生物学因素在BV复发中的作用据我们所知，这是第一次机械地研究 在纵向研究中评估体内BV复发的基础因素，具体地说，使用 综合、多学科方法(行为学、微生物学和免疫学)。我们将使用 尖端技术来测量这些与BV复发相关的潜在机制。研究结果将 至关重要的是制定有针对性的干预战略，以防止BV复发，从而更好地保护妇女 免受艾滋病毒和性传播感染的侵害。

Abstract Bacterial vaginosis (BV), the most common health condition affecting the female reproductive tract, significantly increases the risk of HIV and STI acquisition in women. BV is characterized by changes in the composition of the vaginal bacteria (microbiota), with a reduction in healthy vaginal Lactobacillus species and an increase in gram negative anaerobic bacteria. Women with BV have impaired female reproductive tract mucosal immune responses with increased HIV target cells, as well as decreased epithelial integrity; all which lead to increased HIV risk. Furthermore, a recent study demonstrated that BV-associated bacteria can directly hydrolyze drugs used for HIV prevention, setting up conditions that undermine treatment efficacy. Current antibiotic-based treatments for BV result in failure of treatment or recurrence in the majority of women. Behavioral (sexual behaviors and intravaginal hygiene practices such as intravaginal douching), bacterial factors (microbiome and virome), and host biological factors (mucosal immune responses and inflammation), all may underscore BV recurrence. In this study, we will assess the mechanisms underlying BV recurrence in a unique cohort of reproductive age women (18-45 years) with BV. Reproductive age women with BV will be provided BV treatment and followed longitudinally (one and six months post-BV treatment). Study aims are: 1) To evaluate the role of intravaginal hygiene practices on BV recurrence; 2) To evaluate the role of the vaginal microbiome and virome, and antibiotic metabolism by vaginal bacteria, on BV recurrence; and 3) To evaluate the role of host biological factors on BV recurrence. To our knowledge, this is the first study to mechanistically assess factors that underlie BV recurrence in vivo in a longitudinal study, and specifically, using a comprehensive, multidisciplinary approach (behavioral, microbiological, and immunological). We will use cutting edge technologies to measure these potential mechanisms relative to BV recurrence. Study results will be critical to develop targeted intervention strategies to prevent BV recurrence and thus, better protect women from HIV and STIs.