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健康状况， 显着增加女性感染艾滋病毒和性传播感染的风险。 BV的特点是变化 阴道细菌（微生物群）的组成，健康阴道乳酸菌种类减少， 革兰氏阴性厌氧菌增加。患有 BV 的女性女性生殖道受损 粘膜免疫反应导致 HIV 靶细胞增加，以及上皮完整性降低；所有这一切 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 水解用于预防艾滋病毒的药物，造成破坏治疗效果的条件。当前 大多数女性基于抗生素的 BV 治疗会导致治疗失败或复发。 行为（性行为和阴道内卫生习惯，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 复发。在这项研究中，我们将评估 BV 复发的机制 患有 BV 的育龄女性（18-45 岁）的独特群体。患有 BV 的育龄妇女将 提供 BV 治疗并进行纵向随访（BV 治疗后 1 个月和 6 个月）。研究目的是：1） 评估阴道内卫生习惯对 BV 复发的作用； 2）评估阴道的作用 微生物组和病毒组以及阴道细菌的抗生素代谢对 BV 复发的影响； 3) 评估 宿主生物因素对 BV 复发的作用。据我们所知，这是第一个机械地研究 在纵向研究中评估 BV 体内复发的因素，特别是使用 综合的、多学科的方法（行为学、微生物学和免疫学）。我们将使用 测量这些与 BV 复发相关的潜在机制的尖端技术。研究结果将 制定有针对性的干预策略以预防 BV 复发至关重要，从而更好地保护女性 来自艾滋病毒和性传播感染。

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.