Sexual trauma and HIV susceptibility among women: the role of stress and genital immunity

项目摘要 大量的流行病学数据证明了性暴力与感染艾滋病毒之间的联系 通过直接和间接的途径。然而，解释这种关联的潜在生物学机制 是不太被理解的。性暴力可能通过破坏宫颈阴道 上皮和放大局部炎症和免疫激活。性暴力也可能改变 下丘脑-垂体-肾上腺（HPA）轴导致先天和适应性免疫系统的变化 女性生殖道（FGT）和宫颈阴道上皮健康的改变。与成人相比 由于生殖器粘膜的差异， 子宫颈异位和高基线炎症使女孩更容易受到压力的不利影响。 我们的初步数据表明，最近和慢性的性暴力病例都会导致关键的 FGT免疫介质有可能影响HIV易感性。建立更好的理解 FGT中的免疫与HPA轴失调之间的相关性，以及 对制定战略，消除少女与成年妇女之间的不良关系至关重要。 粘膜损伤导致的性创伤的影响，以减少艾滋病毒感染的风险。与 最后，我们将：1）评估性创伤对FGT免疫的影响; 2）评估性创伤对FGT免疫的影响。 3）确定HPA轴失调影响中枢和外周HPA轴的程度; 性创伤后的FGT免疫力;以及4）检查是否与性暴力有关的风险因素（即， 性危险行为、物质使用、心理健康）与HPA轴失调和FGT相关 性创伤后少女和成年妇女的免疫力。我们将进一步确定这些 在创伤性事件之后，关联随着时间的推移而改变。我们的跨专业团队将处理一个案件- 在14-19岁少女（n=30; 15例病例和15例对照）和成人中进行随访的对照研究 20岁及以上女性（n=30; 15例病例和15例对照）。所有参与者将完成一项定量调查 以及基线、1个月和3个月随访访视时的临床评估。拟议的研究将推动 2016年度通过“女性生殖道与艾滋病的关系研究”的NIH艾滋病相关研究计划 免疫功能，包括性暴力导致的生殖器损伤，对艾滋病毒风险的影响”，并对RFA高度敏感- AI-15-058，“开展研究，解决我们对生殖健康的理解方面的差距， 成熟影响艾滋病毒易感性。”这项研究的结果将有助于未来的假设驱动 纵向研究和制定安全有效的生物医学预防战略。

Project Summary Extensive epidemiological data has documented an association between sexual violence and HIV acquisition through direct and indirect pathways. However, the underlying biological mechanism to explain this association is less understood. Sexual violence may contribute to HIV acquisition by disrupting the cervicovaginal epithelium and magnifying local inflammation and immune activation. Sexual violence may also alter the hypothalamic-pituitary-adrenal (HPA) axis resulting in changes to the innate and adaptive immune system in the female genital tract (FGT) and alterations to cervicovaginal epithelial health. When compared to adult women, adolescent girls may be at heightened biological risk due to differences in the genital mucosa such as cervical ectopy and high baseline inflammation rendering girls more vulnerable to adverse effects of stress. Our preliminary data indicate both recent and chronic cases of sexual violence cause dysregulation of critical FGT immune mediators that have the potential to affect HIV susceptibility. Establishing a better understanding of the correlation between immunity in the FGT and the dysregulated HPA axis, as well as the differences between adolescent girls and adult women is critical for the development of strategies to counter the adverse effects of sexual trauma resulting from mucosal injury in efforts to reduce the risk of HIV acquisition. To that end, we will: 1) assess the impact of sexual trauma on FGT immunity; 2) assess the impact of sexual trauma on the central and peripheral HPA axis; 3) determine the extent to which the dysregulated HPA axis affects FGT immunity following sexual trauma; and 4) examine whether risk factors linked to sexual violence (i.e., sexual risk behaviors, substance use, mental health) are associated with HPA axis dysregulation and FGT immunity in adolescent girls and adult women post-sexual trauma. We will further determine how these associations change over time following the traumatic event. Our multi-disciplinary team will conduct a case- control study with follow-up among adolescent girls aged 14-19 n=30; 15 cases and 15 controls) and adult women aged 20 and older (n=30; 15 cases and 15 controls). All participants will complete a quantitative survey and clinical assessment at baseline, 1- and 3-month follow-up visits. The proposed research will advance the FY2016 Trans-NIH Plan for HIV-related Research by “examining the relationship of the female genital tract immune function, including genital injury due to sexual violence, to HIV risk” and is highly responsive to RFA- AI-15-058 by “conducting research that addresses the gaps in our understanding of how reproductive maturation impacts HIV susceptibility.” Findings from this research will facilitate future hypothesis-driven longitudinal research and development of safe and efficacious biomedical prevention strategies.