Formative research on PrEP provision in U.S. HIV-serodiscordant couples

描述（由申请人提供）：在美国估计有20万对艾滋病毒血清不一致的异性恋夫妇，每年大多数异性性行为获得的艾滋病毒感染（> 12，000）可归因于这些夫妇内的传播。只有大约三分之一的血清不一致的夫妇始终使用避孕套，不到一半的感染伴侣保持检测不到的病毒载量。艾滋病毒暴露前预防（PrEP）是一种有效的和有前途的新方法，以减少血清不一致的夫妇之间的性传播艾滋病毒。2012年，FDA批准每日口服FTC/TDF（Truvada）作为第一种用于艾滋病毒预防适应症的PrEP药物。疾病预防控制中心已确定艾滋病毒未感染者血清不一致的关系作为PrEP在美国的优先事项，然而，这一组尚未被列入之前的PrEP临床试验或示范项目，许多关键问题仍然没有得到回答，关于PrEP可接受性的水平和决定因素，药物依从性，健康影响，临床监测，性行为的变化，并保留护理。这一根本性的知识差距是一个重大的障碍，以实现公共卫生福利的准备。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，每天口服Truvada/准备之间的艾滋病毒血清不一致的异性恋夫妇在高流行社区在纽约市（NYC）。在纽约市（和全国）推出口服PrEP尚处于早期阶段，医疗服务提供者和其他利益相关者刚刚开始面对实施挑战并提出解决方案。这提供了一个历史性的机会来研究跨临床站点的实施过程并确定因素 在与PrEP结果相关的多个层面（提供者，夫妇，个人）。将通过临床研究中心网络（N=18）招募HIV阴性PrEP启动者（n = 270）及其HIV阳性指数伴侣（n=270），并随访18个月，每3个月进行一次评估。PrEP实施数据将从临床提供者收集，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。还将从未启动PrEP的样本中收集数据（n=100）。定性访谈将进行与供应商和夫妇的子集。具体目的是描述时间模式，并确定PrEP结局的多层次决定因素，包括（a）吸收，可接受性和护理保留，（B）药物依从性，（c）安全性和毒性， (d)遵守艾滋病毒检测和临床监测，以及（e）改变性风险行为。这项研究是创新的，因为它采用了生物行为多站点纵向设计，以确定影响PrEP实施结果的关键因素在多个层面上的供应商（例如， 策略、过程），二元（例如，伙伴和关系属性），以及个人（例如，PrEP用户特征）-在未充分研究的组中。这项研究的意义和潜在影响在于它能够通过告知政策，推进循证临床实践，指导干预措施的开发，为PrEP建模提供数据，并指导未来对PrEP交付模型的研究来推进该领域。

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 (e.g., 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.