PrEP implementation with US HIV-serodiscordant couples: Couples PrEP Demo Project

 描述(由申请人提供)：据估计，美国有200,000对艾滋病毒血清不一致的异性恋夫妇，每年通过异性行为获得的艾滋病毒感染(&gt；12,000例)可归因于在这些夫妇中的传播。只有大约三分之一的血清不一致夫妇始终如一地使用避孕套，只有不到一半的感染者保持着无法检测到的病毒载量。艾滋病毒暴露前预防(PrEP)是一种有效和有前景的新方法，可以减少性获得性艾滋病毒在血清不一致夫妇中的传播。2012年，FDA批准每日口服FTC/TDF(Truvada)作为第一个用于艾滋病毒预防适应症的PrEP药物。CDC已将血清不一致关系中的HIV非感染者确定为美国PrEP的优先事项。然而，这一群体尚未被纳入先前的PrEP临床试验或示范项目，许多关键问题仍未得到回答，这些问题涉及PrEP的接受度和决定因素、用药依从性、健康影响、临床监测、性行为变化和护理保留。知识上的这一根本差距是实现PrEP公共卫生益处的一个重大障碍。为了填补这一空白，我们提出了一个混合方法的前瞻性开放标签示范项目，在纽约市(NYC)高发社区的HIV血清不一致的异性夫妇中进行每日口服Truvada/PrEP的示范项目。口服预防接种计划在纽约市(和全国)的推广还处于早期阶段，卫生服务提供者和其他利益攸关方才刚刚开始面对实施挑战并提出解决方案。这为研究跨临床站点的实施过程并确定因素提供了历史性的机会 在多个层面(提供者、夫妇、个人)与PrEP结果相关联。艾滋病毒阴性的PrEP启动者(n=270)及其艾滋病毒阳性指数伙伴(n=270)将通过临床站点网络(N=18)招募，并跟踪18个月，每隔3个月进行一次评估。PREP实施数据将从临床提供商收集，行为、生物和医疗记录数据将从PrEP用户和索引合作伙伴收集。数据也将从那些没有启动PrEP的人(n=100)中收集。定性访谈将与提供者和夫妇的子集进行。具体目的是描述时间模式并确定PrEP结果的多水平决定因素，包括(A)在护理中的摄取率、可接受性和保留率，(B)用药依从性，(C)安全性和毒性， (D)遵守艾滋病毒检测和临床监测，以及(E)改变为性危险行为。这项研究的创新之处在于，它采用生物行为多点纵向设计，在一个未被研究的群体中，确定在多个层面上影响PrEP实施结果的关键因素--提供者(例如，政策、程序)、二元(例如，合作伙伴和关系属性)和个人(例如，PrEP用户特征)。这项研究的意义和潜在影响在于，它能够通过为政策提供信息、推进循证临床实践、指导干预措施的发展、为PrEP建模提供数据以及指导未来PrEP交付模式的研究来推动该领域的发展。

 DESCRIPTION (provided by applicant): There are an estimated 200,000 HIV-serodiscordant heterosexual couples in the U.S. and the majority of heterosexually acquired HIV infections each year (>12,000) can be attributed to transmission within these couples. Only about one-third of serodiscordant couples use condoms consistently and less than half of infected partners maintain undetectable viral loads. HIV pre-exposure prophylaxis (PrEP) represents an efficacious and promising new approach to reduce the spread of sexually acquired HIV among serodiscordant couples. In 2012, the FDA approved daily oral FTC/TDF (Truvada) as the first PrEP agent for HIV prevention indication. The CDC has identified HIV-uninfected persons in serodiscordant relationships as a priority for PrEP in the U.S. Yet, this group has not been included in prior PrEP clinical trials or demonstration projects and many critical questions remain unanswered regarding the levels and determinants of PrEP acceptability, medication adherence, health effects, clinical monitoring, changes in sexual behavior, and retention in care. This fundamental gap in knowledge represents a significant barrier to realizing the public health benefits of PrEP. To fill this gap, we propose a mixed-methods prospective open-label demonstration project of daily oral Truvada/PrEP among HIV-serodiscordant heterosexual couples in high-prevalence communities in New York City (NYC). Roll-out of oral PrEP in NYC (and nationally) is at an early stage and health providers and other stakeholders are just beginning to confront and propose solutions to implementation challenges. This provides an historic opportunity to study the implementation process across clinical sites and identify factors at multiple levels (provider, couple, individual) associated with PrEP outcomes. HIV-negative PrEP initiators (n=270) and their HIV- positive index partners (n=270) will be recruited through a network of clinical sites (N=18) and followed for 18 months with assessments at 3-month intervals. PrEP implementation data will be collected from clinical providers and behavioral, biological, and medical record data will be collected from PrEP users and index partners. Data will also be collected from a sample of those who do not initiate PrEP (n=100). Qualitative interviews will be conducted with a subset of providers and couples. The specific aims are to describe the temporal patterns and identify multilevel determinants of PrEP outcomes, including (a) uptake, acceptability and retention in care, (b) medication adherence, (c) safety and toxicity, (d) compliance with HIV testing and clinical monitoring, and (e) changes is sexual risk behavior. This research is innovative in that it employs a biobehavioral multi-site longitudinal design to identify critical factors affecting PrEP implementation outcomes at multiple levels-provider (e.g., policies, procedures), dyadic (e.g., partner and relationship attributes), and individual (eg., PrEP user characteristics)-in an understudied group. The significance and potential impact of this study is in its capacity to advance the field by informing policy, advancing evidence-based clinical practice, guiding the development of interventions, providing data for PrEP modeling, and directing future research on models of PrEP delivery.