Integrated PrEP and ART delivered in Ugandan public health clinics to improve HIV and ART outcomes for HIV serodiscordant couples

摘要 在过去30年里，在控制艾滋病毒流行病和艾滋病方面取得了巨大进展。 现在已经有了消灭艾滋病的工具。其中最有意义的工具是抗逆转录病毒药物， 艾滋病毒阳性者接受抗逆转录病毒治疗（ART），艾滋病毒阴性者接受暴露前预防（PrEP） 个体每一种都有巨大的好处，艾滋病毒预防证明在控制研究 环境.对于艾滋病毒血清不一致的夫妇，稳定的夫妇，其中一个是艾滋病毒阳性，一个是 艾滋病毒阴性，这两种干预措施可以以综合方式提供，其中PrEP的使用是 鼓励直到艾滋病毒阳性伴侣持续使用抗逆转录病毒疗法，不再 传染性 这一战略几乎消除了艾滋病毒在 在我们最近的示范项目中，有1000对夫妇，但尚不清楚这种干预是否会 由工作人员在公共卫生环境中有效地提供，而无需深入处方 体验.这项研究的初步数据也表明了综合PrEP和ART的效果 在建议开始后12个月内，抗逆转录病毒治疗启动率接近90%的战略 坚持抗逆转录病毒疗法，90%以上的艾滋病毒阳性伴侣在6个月内被病毒抑制。 这些比率远远超过乌干达公共卫生诊所的比率。使用PrEP的真正效果 通过模仿行为或其他机制，ART的启动和坚持将是一个令人信服的 推动PrEP作为乌干达艾滋病毒预防政策的一部分并为更多人提供便利的论点 发起并坚持艺术。 通过与乌干达卫生部的密切合作，我们建议实施可扩展的 在公共卫生诊所为艾滋病毒血清不一致的夫妇提供综合的PrEP和ART， 乌干达，坎帕拉。将在各诊所之间以交错的方式开展干预服务 通过一项阶梯楔形群随机试验，提供了一个严格的研究机会， 衡量干预措施对PrEP和ART启动和依从性的影响。测量这些 使用临床记录和生物标志物的结果，我们将招募1248名HIV血清不一致的队列， 夫妻。此外，我们还将收集定性和定量数据，以确定 PrEP服用是一种模型化的行为，有助于ART的使用，并表征PrEP和 ART的使用在夫妇之间相互作用，并估计综合PrEP和ART的计划成本 战略这项研究的结果将提供令人信服的数据，为广泛提供 将艾滋病毒血清不一致夫妇的PrEP和ART作为乌干达国家艾滋病毒方案的组成部分 预防政策。拟议的项目将通过以下方式在乌干达启动PrEP的可持续交付 公共卫生诊所，它有可能展示一个可扩展的和具有成本效益的 为艾滋病毒血清不一致的夫妇提供强有力的艾滋病毒预防工具。

ABSTRACT There has been great progress in the past 30 years towards controlling the HIV epidemic and the tools to end AIDS are now available. One of the most profound tools is antiretrovirals used as HIV treatment (ART) by HIV-positive individuals and pre-exposure prophylaxis (PrEP) by HIV-negative individuals. Each have tremendous benefits for HIV prevention proven in controlled research environments. For HIV serodiscordant couples, stable couples where one is HIV-positive and one is HIV-negative, these two interventions can be delivered in an integrated fashion where PrEP use is encouraged until the point when the HIV-positive partner has sustained use of ART and is no longer infectious. This strategy nearly eliminated HIV transmission within >1000 couples in our recent demonstration project but it is not clear that this intervention would be delivered as effectively in a public health setting by staff without in depth prescribing experience. Preliminary data from this study also suggest an effect of the integrated PrEP and ART strategy on ART initiation with rates close to 90% within 12 months of a recommendation to start and ART adherence with >90% of HIV-positive partners being virally suppressed within 6 months. These rates far exceed those seen in Ugandan public health clinics. A true effect of PrEP use on ART initiation and adherence, through modeled behavior or other mechanisms, would be a compelling argument to drive forward PrEP as part of Ugandan HIV prevention policy and facilitate more people to initiate and adhere to ART. Through close collaboration with the Ugandan Ministry of Health, we propose to implement scalable delivery of integrated PrEP and ART for HIV serodiscordant couples in public health clinics in Kampala, Uganda. Intervention delivery will be launched in a staggered fashion among clinics through a stepped wedge cluster randomized trial providing a rigorous research opportunity to measure the effect of the intervention on PrEP and ART initiation and adherence. To measure these outcomes using clinic records and biomarkers, we will enroll a cohort of 1248 HIV serodiscordant couples. Additionally, we will collect qualitative and quantitative data to determine if PrEP-taking is a modeled behavior that facilitates ART use and characterize the way that PrEP and ART use interact within couples and estimate the programmatic costs of the integrated PrEP and ART strategy. Results from this study will provide compelling data to inform widespread delivery of integrated PrEP and ART for HIV serodiscordant couples as a component of Ugandan national HIV prevention policy. The proposed project will launch sustainable delivery of PrEP in Uganda through public health clinics and it has the potential to demonstrate a scalable and cost-effective approach for providing powerful HIV prevention tools to HIV serodiscordant couples.