Understanding STI and HIV prevention adherence among Kenyan women

摘要 这项K23指导的以患者为导向的研究职业发展奖提案支持为期5年的研究 并为Jenell Stewart博士提供培训计划，以确立自己作为独立调查员的地位，并具有以下方面的专业知识 性传播感染(STI)和艾滋病毒预防。斯图尔特博士是传染病内科医生兼科学家 在低资源环境下致力于性传播感染和艾滋病毒研究的良好记录 具有国际合作经验。对于这项提议，斯图尔特博士将受益于额外的培训， 包括在性传播感染和艾滋病毒预防试验的设计和分析方面的正规课程工作和指导， 性接触和事件驱动的依从性的评估，以及性别力量的混合方法分析 遵守行为中的动态。在过去的十年中，细菌性传播感染的比率在 世界各地的人口。除了艾滋病毒感染风险增加外，肯尼亚年轻妇女的性传播感染也非常高 严重后果的发生率(如盆腔炎、输卵管性不孕、妊娠并发症)。 用抗生素多西环素(DPEP)预防暴露后感染(PEP)是一种新的STI 控制策略和在男男性行为者中进行的dPEP试验正在进行中，一项已完成和 有多个计划。这项K23提案将利用dPEP在妇女中的第一次试验，于#年在肯尼亚启动 2020年1月。与依赖合作伙伴参与的其他STI预防策略不同，按需dPEP 将由妇女控制；然而，对肯尼亚人坚持性传播感染预防行为知之甚少 女人。了解非洲妇女坚持艾滋病毒暴露前预防(PrEP)是关键 准确定义这一人群的有效性以及类似的dPEP遵从性将是重要的衡量标准 并进行评估。我们假设，提供高依从性的dPEP将大大降低发病率 细菌性传播感染，特别是沙眼衣原体、梅毒螺旋体和支原体 生殖器。在dPEP Will父母随机试验中对女性生殖支原体的纵向评估 提供有关这一新兴STI的唯一数据。目标1将测量dPEP黏附对细菌STI的影响 在肯尼亚人中利用dPEP与标准降低风险咨询的随机试验进行保护 女性(N=446)使用头发药物浓度跟踪观察12个月以确定依从性 全面的病例队列分析。AIM 2将从以下点评估最近诊断为性传播感染的影响- 对后续纵向预防行为(遵守dPEP和PrEP以及频率)进行的卫生保健STI测试 指没有公寓的性行为)使用自我报告的行为来验证生物指标。目标3将决定如何 性别权力动态与坚持行为有关，使用定量和定量的混合方法分析 初级性关系中性别力量差异的定性测量。这项提案将提供 在妇女中避免细菌性传播感染和艾滋病毒感染引起的发病率和死亡率的重要证据。

ABSTRACT This K23 Mentored Patient-Oriented Research Career Development Award proposal supports a 5-year research and training program for Dr. Jenell Stewart to establish herself as an independent investigator with expertise in sexually transmitted infection (STI) and HIV prevention. Dr. Stewart is an Infectious Diseases physician-scientist with a strong track record of dedication to STI and HIV research in low-resource settings and extensive experience in international collaborations. For this proposal, Dr. Stewart will benefit from additional training, including formal course work and mentorship, in design and analysis of STI and HIV prevention trials, assessment of sexual exposures and event-driven adherence, and mixed-methods analysis of gendered power dynamics in adherence behavior. In the past decade, rates of bacterial STIs have increased markedly in populations worldwide. In addition to increased risk of HIV infections, young Kenyan women have very high STI rates with severe consequences (e.g., pelvic inflammatory disease, tubal infertility, complications of pregnancy). Post-exposure prophylaxis (PEP) with the antibiotic doxycycline (dPEP) has been proposed as a novel STI control strategy, and dPEP trials among men who have sex with men are ongoing with one completed and multiple planned. This K23 proposal will leverage the first trial of dPEP among women, launching in Kenya in January 2020. In contrast to other STI prevention strategies that rely on partner participation, on-demand dPEP would be woman-controlled; however, little is known about adherence behavior to STI prevention among Kenyan women. Understanding adherence to HIV pre-exposure prophylaxis (PrEP) in African women was key to accurately defining effectiveness in this population, and similarly dPEP adherence will be important to measure and evaluate. We hypothesize that provision of dPEP with high adherence will substantially reduce the incidence of bacterial STIs, particularly Chlamydia trachomatis as well as Treponema pallidum and Mycoplasma genitalium. The longitudinal evaluation of M. genitalium in women in the parent randomized trial of dPEP will provide unique data on this emerging STI. Aim 1 will measure the effect of dPEP adherence on bacterial STI protection by leveraging a randomized trial of dPEP versus standard risk-reduction counseling among Kenyan women (N=446) followed for 12 months using hair drug concentrations to determine adherence in a comprehensive case-cohort analysis. Aim 2 will assess the impact of a recent diagnosis with an STI from point- of-care STI testing on subsequent longitudinal prevention behavior (adherence to dPEP and PrEP and frequency of condomless sex) using self-reported behavior validated against biological measures. Aim 3 will determine how gendered power dynamics relate to adherence behavior using a mixed methods analysis of quantitative and qualitative measures of gendered power differentials in primary sexual relationships. This proposal will provide important evidence to avert morbidity and mortality from bacterial STI and HIV acquisition among women.