Optimizing Antiretroviral-Based Prevention by Enhancing PrEP Adherence in MSM

描述（由申请人提供）：背景：经过30年的艾滋病流行，在过去的几个月里，一种新的生物医学预防方法正在出现。然而，在这两项具有里程碑意义的研究中，AC的疗效因不依从性而显著减弱。自艾滋病开始流行以来，男同性恋者一直是，并将继续是，在美国和世界各地面临新感染风险的最大人群之一（3,4）。因此，为了使AC作为一种有效的公共卫生干预措施，必须制定适合文化的方案，以优化依从性。设计：本R34将适应并试点测试一种干预措施，以最大限度地提高MSM患者口服AC的依从性，为未来的R01测试生物医学和行为预防联合干预的效果奠定基础。我们建议：1)进行形成性的定性研究，以更好地了解对交流有效性的看法、交流使用的障碍和促进因素，并了解上下文变量，如高风险的MSM如何将交流纳入其伴侣选择的决策中（即在稳定的伙伴关系中使用与匿名伙伴使用）。因此，我们将与参与芬威健康中心iPrEx或CDC PrEP研究的男同性恋者进行焦点小组讨论，我们还将征求社区咨询委员会和其他主要男同性恋者利益相关者的意见；2)利用这些数据开发并公开试点PrEP依从性干预措施，该干预措施可与高危MSM的PrEP临床监测一起提供；3)与主动的、时间匹配的对照相比，开展一项PrEP一揽子计划的试点随机对照试验。主要结果将是依从性，通过药物事件监测系统（MEMS）上限来衡量，次要结果将是与PrEP相关的性风险补偿减少。干预开发过程：拟议的项目遵循干预开发的迭代方法，首先进行形成性研究，其次公开试点干预并改进它，第三，通过进行试点随机对照试验。这将为全面试验奠定基础，以测试执行PrEP的最佳方法并优化依从性。创新：PrEP是第一个生物医学预防干预措施，已被证明对降低男男性行为者的艾滋病毒发病率有效；但最佳实施需要同时进行行为干预，正如iPrEx研究中与HIV发病率相关的大量不依从性所证明的那样。拟议的研究将允许制定最佳的AC预防方案，包括结合生物医学和行为方法来预防艾滋病毒。

DESCRIPTION (provided by applicant): Background: After 30 years of the HIV epidemic, in the past few months, a new approach to biomedical prevention is emerging. Antiretroviral chemoprophylaxis (AC) has been demonstrated to be effective by protecting men who have sex with men (MSM) when co-formulated tenofovir-emtricitabine (TDF/FTC) is used orally every day as pre-exposure prophylaxis (PrEP) (iPrEx study) (1); and for at risk South African women when 1% tenofovir vaginal gel is used pericoitally (2). However, in both these landmark studies, the efficacy of AC was significantly attenuated by non-adherence. Since the beginning of the epidemic, MSM have been, and continue to be, one of the largest groups of people at risk for new infections in the U.S. and around the world (3, 4). Thus, for AC to be effective as a public health intervention, culturally tailored programs designed to optimize adherence must be developed. Design: This R34 will adapt and pilot test an intervention to maximize oral AC adherence in MSM, laying the groundwork for a future R01 to test the efficacy of a combined biomedical and behavioral prevention intervention. We propose to: 1) conduct formative, qualitative research to better understand perceptions of AC efficacy, barriers and facilitators of AC use, and to understand contextual variables such as how high-risk MSM would integrate AC into their decision-making regarding partner selection (i.e. use in stable partnerships vs. use with anonymous partners). Accordingly, focus groups will be conducted with MSM who participated in the iPrEx or CDC PrEP study at Fenway Health, and we also will solicit input from our Community Advisory Board and other key MSM stakeholders; 2) use these data to develop and openly pilot a PrEP adherence intervention that can be delivered along with PrEP clinical monitoring for high-risk MSM; and 3) to conduct a pilot randomized controlled trial of this PrEP package compared to an active, time-matched control. The primary outcome will be adherence, as measured by medication event monitoring systems (MEMS) caps, and the secondary outcome will be decreased sexual risk compensation associated with PrEP. Intervention development process: The proposed project follows an iterative approach for intervention development by first conducting formative research, second openly piloting the intervention and refining it, and third, by conducting a pilot RCT. This will lay the groundwork for a full-scale trial to test the optimal methods to administer PrEP and to optimize adherence. Innovation: PrEP is the first biomedical prevention intervention to have been shown to be effective in decreasing HIV in incidence in MSM; but optimal implementation will require concurrent behavioral intervention, as evidenced by the substantial non-adherence associated with HIV incidence in the iPrEx study. The proposed study will allow for the development of an optimal AC prevention package, including combined biomedical and behavioral approaches to HIV prevention. PUBLIC HEALTH RELEVANCE: MSM are by far disproportionately at risk for HIV in the U.S. and other Western settings, and significantly impacted by HIV in international settings. Antiretroviral chemoprophylaxis (AC) has been shown to decrease incident infections, but adherence has been suboptimal, impeding the full benefit of the medication. By combining an evidence-based behavioral intervention with the provision of AC in clinical settings, a combined biobehavioral intervention is likely to be an effective strategy to reduce new HIV infections among MSM.