PrEP and dPEP: Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis

PrEP 和 dPEP：强力霉素暴露后预防，用于使用 HIV 暴露前预防来预防肯尼亚妇女的性传播感染

• 批准号: 10682572
• 负责人: Elizabeth Anne BUKUSI
• 金额: $ 89.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10682572
• 关键词: AIDS prevention; Accounting; Adherence; Africa; African; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Behavioral; Benefits and Risks; Blinded; Calculi; Chlamydia; Chlamydia trachomatis; Clinical Research; Clinical Trials; Cost Measures; Counseling; Country; Data; Disinhibition; Doxycycline; Epidemic; Equilibrium; Europe; Evaluation; Face; France; Fright; Future; Gonorrhea; HIV; HIV Infections; HIV risk; Hand; Health; Health Benefit; Incidence; Income; Infection Control; Instruction; Intervention Trial; Kenya; Laboratories; Measures; Methods; Molecular; Morbidity - disease rate; Neisseria gonorrhoeae; Outcome; Partner Notification; Patient Self-Report; Pelvic Inflammatory Disease; Population; Population Intervention; Populations at Risk; Pregnancy Complications; Prevention; Prevention strategy; Preventive service; Prophylactic treatment; Reporting; Resistance; Risk; Risk Assessment; Risk Reduction; STI prevention; Safety; Science; Services; Sex Behavior; Sexually Transmitted Diseases; Syphilis; Testing; Tetracycline Resistance; Time; Treponema pallidum; Woman; Work; adverse pregnancy outcome; aged; arm; budget impact; cost; cost effective; cost effectiveness; cost estimate; effectiveness evaluation; experience; falls; high risk; high risk population; incremental cost; infection rate; innovation; interest; men who have sex with men; mortality; multidisciplinary; novel; open label; pathogen; pill; pre-exposure prophylaxis; pregnant; prevention service; programs; randomized trial; scale up; sexual HIV transmission; standard of care; tubal infertility; willingness

ABSTRACT In the past decade, HIV pre-exposure prophylaxis (PrEP) has demonstrated high HIV protection among at-risk groups, with the first indications that PrEP may be reducing population-level new HIV infections. At the same time, rates of curable sexually transmitted infections (STIs) have increased markedly in populations worldwide, and PrEP-taking populations, including in our preliminary data among African women, have been found to have very high STI rates. Post-exposure prophylaxis (PEP) with the antibiotic doxycycline (dPEP) has been proposed as a novel STI control strategy. A recent open-label clinical trial of dPEP among PrEP-taking men who have sex with men (MSM) in France found a 47% relative reduction in new bacterial STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum), with >70% protection for C. trachomatis and T. pallidum but expectedly no protection for N. gonorrhoeae given high rates of tetracycline resistance in Europe; two new studies of dPEP among MSM are planned for 2019. African women face disproportionate risk from overlapping HIV-STI epidemics, with STI rates comparable to MSM in high-income countries and with consequences (pelvic inflammatory disease, tubal infertility, complications of pregnancy) arguably more severe than those faced by MSM. In contrast to other STI prevention strategies that rely on partner participation, on-demand dPEP would be woman-controlled, and doxycycline has evidence of safety for use by women. We propose to conduct the first study evaluating dPEP to prevent STIs in PrEP-taking African women, who are a priority population for STI prevention, given high risk and engagement in longitudinal prevention services. STI PEP carries substantial potential benefits but also important potential risks, and we have framed our work as capturing key data to inform the risk-benefit calculus for this cutting-edge question. We hypothesize that dPEP will substantially reduce the incidence of curable STIs, particularly C. trachomatis, the most common bacterial STI and the one responsible for greatest morbidity. STI dPEP carries potential risk of antimicrobial resistance, which we have considered: C. trachomatis resistance has never been seen worldwide, making new resistance from dPEP unlikely, but N. gonorrhoeae tetracycline resistance is common in Kenya, and for that reason we hypothesize dPEP may provide little protection for that pathogen but will also not generate new resistance. In addition to resistance risk, data are needed to determine whether dPEP is safe, acceptable, adhered to, and affordable. Aim 1 will determine the benefit of dPEP to reduce the incidence of curable STIs through an open-label 1:1 randomized trial of dPEP versus standard of care among 446 women aged 18-30 taking PrEP. Aim 2 will assess associated risks of dPEP by exploring a) safety, b) acceptability, c) adherence, and d) resistance, using novel and rigorous behavioral and laboratory science methods. Aim 3 will measure the cost of dPEP and estimate the cost per case averted, budget impact, and affordability. If successful, our study will provide the first evidence for an innovative, low-cost strategy to avert substantial morbidity due to curable STIs in this vulnerable, high-risk population.

抽象的 在过去的十年中，艾滋病毒暴露前预防 (PrEP) 已证明对高危人群具有较高的艾滋病毒保护作用 初步迹象表明，PrEP 可能会减少人口层面的新发艾滋病毒感染。同时 随着时间的推移，全世界人口中可治愈的性传播感染（STI）的比率显着增加， 研究发现，接受 PrEP 的人群，包括我们在非洲妇女中的初步数据， 性传播感染率非常高。已提议使用抗生素多西环素（dPEP）进行暴露后预防（PEP） 作为一种新颖的 STI 控制策略。最近一项在接受 PrEP 的有性行为的男性中进行的 dPEP 开放标签临床试验 法国男性 (MSM) 发现新细菌性传播感染（沙眼衣原体、 淋病奈瑟菌或梅毒螺旋体），对沙眼衣原体和梅毒螺旋体具有 >70% 的保护作用，但 鉴于欧洲四环素耐药率很高，预计淋病奈瑟菌不会受到保护；两个新的 计划于 2019 年对 MSM 进行 dPEP 研究。非洲女性面临着不成比例的重叠风险 HIV-STI 流行病，在高收入国家，STI 发病率与 MSM 相当，并产生后果（盆腔 炎症性疾病、输卵管不孕症、妊娠并发症）可能比以下情况更严重 男同性恋者。与依赖合作伙伴参与的其他性传播感染预防策略相比，按需 dPEP 将 由女性控制，多西环素有证据表明女性使用安全。我们建议进行 第一项评估 dPEP 预防接受 PrEP 的非洲女性性传播感染的研究，她们是性传播感染的重点人群 鉴于高风险和参与纵向预防服务。 STI PEP 具有重大意义 潜在的好处，但也有重要的潜在风险，我们将我们的工作框架定为捕获关键数据以提供信息 这个前沿问题的风险收益计算。我们假设 dPEP 将大大减少 可治愈性传播感染的发病率，特别是沙眼衣原体，它是最常见的细菌性传播感染，也是致病原因之一 以获得最大的发病率。 STI dPEP 具有潜在的抗菌药物耐药性风险，我们已经考虑过：C. 沙眼衣原体耐药性在世界范围内从未出现过，因此 dPEP 不太可能产生新的耐药性，但 N. 淋球菌四环素耐药性在肯尼亚很常见，因此我们假设 dPEP 可能会提供 对这种病原体几乎没有保护作用，但也不会产生新的抵抗力。除了阻力风险之外，数据 需要确定 dPEP 是否安全、可接受、坚持且负担得起。目标 1 将确定 通过开放标签 1:1 dPEP 随机试验，了解 dPEP 在降低可治愈性传播感染发病率方面的益处 与 446 名 18-30 岁服用 PrEP 的女性的护理标准相比。目标 2 将评估 dPEP 的相关风险 通过探索 a) 安全性、b) 可接受性、c) 坚持性和 d) 抵抗性，使用新颖且严格的行为和 实验室科学方法。目标 3 将衡量 dPEP 的成本并估计避免每个病例的成本、预算 影响力和承受能力。如果成功，我们的研究将为创新、低成本策略提供第一个证据 避免这一脆弱的高危人群因可治愈的性传播感染而大量发病。