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

美国 HIV 血清不一致夫妇实施 PrEP：夫妇 PrEP 演示项目

• 批准号: 9150661
• 负责人: James M McMahon
• 金额: $ 67.8万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9150661
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Acute; Address; Adherence; Adult; Adverse effects; Affect; Anti-Retroviral Agents; Antiretroviral resistance; Behavioral; Biological; Blood; Bone Density; Caring; Centers for Disease Control and Prevention (U.S.); Characteristics; Client; Clinical; Clinical Practice Guideline; Clinical Trials; Communities; Consensus; Couples; Data; Development; Drug Kinetics; Evidence based practice; FDA approved; Frequencies; Fumarates; HIV; HIV Infections; HIV Seropositivity; HIV-1; Health; Health Benefit; Health Personnel; Heterosexuals; High Prevalence; Human immunodeficiency virus test; Impairment; Individual; Injecting drug user; Intervention; Interview; Kidney; Knowledge; Link; Medical Records; Methods; Modeling; Monitor; Neonatal; New York City; Oral; Outcome; Participant; Patient Care; Pattern; Persons; Pharmaceutical Preparations; Phase III Clinical Trials; Policies; Population; Pregnant Women; Prevention; Primary Prevention; Procedures; Process; Prophylactic treatment; Provider; Public Health; Publishing; Recruitment Activity; Regimen; Research; Risk; Risk Behaviors; Safety; Sampling; Science; Sex Behavior; Site; Staging; Surveys; System; Tenofovir; Testing; Toxic effect; Viral Load result; Woman; biobehavior; care delivery; clinical effect; clinical practice; clinical research site; condoms; disorder prevention; emtricitabine; evidence base; high risk; indexing; innovation; knowledge base; longitudinal design; medication compliance; member; men; men who have sex with men; novel strategies; open label; prospective; resistant strain; sex risk; therapy development; transmission process; truvada; uptake

 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.

 描述（由申请人提供）：美国估计有 200,000 对 HIV 血清不一致的异性恋夫妇，每年大多数异性性行为获得的 HIV 感染（>12,000 例）可归因于这些夫妇内部的传播。只有约三分之一的血清不一致夫妇始终使用安全套，不到一半的受感染伴侣保持检测不到的病毒载量。 HIV 暴露前预防 (PrEP) 是一种有效且有前景的新方法，可减少血清不一致的夫妇中性传播 HIV 的传播。 2012 年，FDA 批准每日口服 FTC/TDF (Truvada) 作为第一个用于 HIV 预防适应症的 PrEP 药物。 CDC 已将血清不一致关系中的 HIV 未感染者确定为美国 PrEP 的优先对象。然而，这一群体尚未被纳入之前的 PrEP 临床试验或示范项目中，并且关于 PrEP 可接受性水平和决定因素、药物依从性、健康影响、临床监测、性行为变化和护理保留等许多关键问题仍未得到解答。这种知识上的根本差距是实现 PrEP 公共卫生益处的重大障碍。为了填补这一空白，我们提出了一个混合方法前瞻性开放标签示范项目，在纽约市 (NYC) 高流行社区的 HIV 血清不一致的异性夫妇中每日口服 Truvada/PrEP。纽约市（以及全国）口服 PrEP 的推广还处于早期阶段，卫生服务提供者和其他利益相关者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 与 PrEP 结果相关的多个层面（提供者、夫妇、个人）。 HIV 阴性 PrEP 发起者 (n=270) 及其 HIV 阳性索引伙伴 (n=270) 将通过临床中心网络 (N=18) 招募，并进行为期 18 个月的随访，每 3 个月进行一次评估。 PrEP 实施数据将从临床提供者处收集，行为、生物和医疗记录数据将从 PrEP 用户和索引合作伙伴处收集。数据还将从未启动 PrEP 的样本中收集（n=100）。将与一部分提供者和夫妇进行定性访谈。具体目标是描述时间模式并确定 PrEP 结果的多层次决定因素，包括 (a) 摄取、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) 改变危险性行为。这项研究的创新之处在于，它采用生物行为多站点纵向设计来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、指导干预措施的开发、为 PrEP 建模提供数据以及指导未来 PrEP 传递模型的研究来推动该领域的发展。