HIV self-testing to improve the efficiency of PrEP delivery

摘要 最大限度地提供服务和最大限度地降低提供服务的成本是优化公共卫生影响的关键挑战 暴露前预防（PrEP）用于预防HIV-1。在非洲，PrEP将被添加到已经负担沉重的 卫生基础设施和公共卫生系统提供PrEP的能力将需要提供PrEP 具有成本效益和时间效率。PrEP交付计划将对人员配置需求具有成本敏感性（例如，频繁 诊所就诊），如果机会成本（例如，前往诊所并在诊所等候） 很高。HIV-1检测是PrEP提供的核心：检测高危人群是PrEP启动的第一步， 持续的HIV-1检测对于PrEP提供至关重要。与PrEP一样，HIV-1自我检测是一项新的创新， 改善艾滋病毒-1预防工作的机会尚未充分实现。我们假设HIV-1自身 测试可用于简化PrEP交付-特别是通过减少PrEP遵循的频率- 通过在家中进行自我测试来取代诊所测试，从而增加诊所访问。新的基于全血的HIV-1自体 检测试剂盒可能比口腔液体检测更经济实惠， 信心通过多学科协作团队，我们建议解决关键访问和交付成本问题 通过使用HIV-1自我检测的新模式来应对PrEP的挑战。我们将进行一项个体随机化 在肯尼亚495名开始PrEP的女性和男性中使用非劣效性设计的试验， 分配至：每季度门诊访视，进行门诊血液HIV-1检测（标准治疗组）或6次- 每月门诊访视，在门诊访视之间的宿舍进行HIV-1自测（自测组）; 被分配到自我检测的患者将被分配到基于口腔液体或基于血液的检测。人口将 包括HIV-1血清不一致异性恋夫妇（n=165例HIV-1未感染男性和n=165例HIV-1感染者 未感染的妇女）和HIV-1未感染的高危妇女（n=165）。6个月和12个月时的结果将是 PrEP依从性（血液样本中的PrEP检测和获得再填充的持续性），完成HIV-1 测试和安全性（包括副作用和社会危害）。我们将整合混合方法的工作， 用户体验、偏好、提供者选择、障碍和与HIV-1自我检测相关的促进因素 PrEP背景下，探索两种自我检测方式（血液和口腔液）的印象，并考虑 性别和夫妻状况对我们研究结果的影响。最后，我们还将使用微成本计算和数学 建模以评估HIV-1自我检测的成本和成本效益，以优化PrEP的交付。结合 自我检测和PrEP结合了两种尖端干预措施，以及简单的HIV-1自我检测策略 在这种应用中，可以提高PrEP的成本效益，覆盖范围和影响，而不会牺牲HIV-1保护 和安全性鉴于这问题的时效性，并根据我们的经验，我们建议 在3.5年内完成这项工作。

ABSTRACT Maximizing access and minimizing costs of delivery are key challenges for optimizing the public health impact of pre-exposure prophylaxis (PrEP) for HIV-1 prevention. In Africa, PrEP will be added to an already-burdened health infrastructure and the ability of public health systems to afford PrEP will necessitate making its delivery cost-effective and time-efficient. PrEP delivery programs will be cost-sensitive to staffing needs (e.g., frequent clinic visits), and patients may not continue PrEP if the opportunity costs (e.g., travel to and waiting in clinics) are high. HIV-1 testing is central to PrEP delivery: testing at-risk persons is the first step for PrEP initiation and ongoing HIV-1 testing is essential for PrEP delivery. Like PrEP, HIV-1 self-testing is a new innovation and its opportunities to improve HIV-1 prevention have not yet been fully realized. We hypothesize that HIV-1 self- testing could be used to streamline PrEP delivery – specifically through decreasing the frequency of PrEP follow- up clinic visits by having self-tests at home replace clinic-based testing. New whole blood-based HIV-1 self- testing kits are potentially more affordable than oral fluid tests and may result in greater patient and provider confidence. With a multidisciplinary collaborative team, we propose to address key access and cost of delivery challenges for PrEP by using the new modality of HIV-1 self-testing. We will conduct an individually-randomized trial using a non-inferiority design among 495 women and men in Kenya initiating PrEP who will be randomly assigned to either: quarterly clinic visits with in-clinic blood-based HIV-1 testing (standard of care arm) or six- monthly clinic visits with HIV-1 self-testing at home for quarters between clinic visits (self-testing arm); those assigned to self-testing will be assigned to either oral fluid-based or blood-based testing. The population will include heterosexual HIV-1 serodiscordant couples (n=165 with HIV-1 uninfected men and n=165 with HIV-1 uninfected women) and HIV-1 uninfected women at risk (n=165). The outcomes at 6 and 12 months will be PrEP adherence (PrEP detection in blood samples and persistence in obtaining refills), completion of HIV-1 testing, and safety (including side effects and social harm). We will integrate mixed-methods work to understand user experiences, preferences, provider options, barriers, and facilitators related to HIV-1 self-testing within the PrEP context, to explore impressions of the two self-testing modalities (blood and oral fluid), and to consider the effect of gender and couple status on our findings. Finally, we will also use microcosting and mathematical modeling to assess the cost and cost-effectiveness of HIV-1 self-testing to optimize PrEP delivery. Combining self-testing and PrEP brings together two cutting-edge interventions, and the simple HIV-1 self-testing strategy in this application could improve PrEP’s cost-effectiveness, reach, and impact without sacrificing HIV-1 protection and safety. Given the time-sensitive nature of this question, and leveraging our experience, we propose to conduct this work in 3.5 years.