Optimizing Antiretroviral-Based Prevention by Enhancing PrEP Adherence in MSM

描述（由申请人提供）：背景：经过30年的艾滋病毒流行，在过去的几个月里，一种新的生物医学预防方法正在出现。已证明抗逆转录病毒化学预防（AC）通过保护男性同性性行为（MSM），每天口服替诺福韦-恩曲他滨（TDF/FTC）作为暴露前预防（PrEP）（iPrEx研究）（1）;以及当1%替诺福韦阴道凝胶用于宫颈周围时（2），对处于风险中的南非女性有效。然而，在这两项具有里程碑意义的研究中，AC的疗效因不依从而显著减弱。自疫情开始以来，男男性接触者一直是，并继续是，在美国和世界各地的新感染的风险最大的人群之一（3，4）。因此，AC是有效的公共卫生干预，文化定制的方案，旨在优化遵守必须开发。设计图：该R34将调整并试点测试一种干预措施，以最大限度地提高MSM的口服AC依从性，为未来的R 01测试生物医学和行为预防综合干预措施的功效奠定基础。我们建议：1）进行形成性、定性研究，以更好地了解对AC有效性的看法，AC使用的障碍和促进因素，并了解背景变量，例如高风险MSM如何将AC纳入他们关于伴侣选择的决策（即在稳定的伴侣关系中使用与匿名伴侣一起使用）。因此，焦点小组将与在芬威健康参加iPrEx或CDC PrEP研究的MSM进行，我们还将征求我们的社区咨询委员会和其他主要MSM利益相关者的意见; 2）使用这些数据来开发和公开试点PrEP依从性干预措施，该干预措施可以与PrEP临床监测一起沿着高风险MSM;和3）进行一个试点随机对照试验，这种PrEP包相比，积极的，时间匹配的控制。主要结果将是依从性，作为衡量的药物事件监测系统（MEMS）的上限，和次要结果将减少性风险补偿与PrEP. Intervention开发过程：拟议的项目遵循一个迭代的方法进行干预开发，首先进行形成性研究，第二次公开试点干预和完善，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，以测试管理PrEP和优化依从性的最佳方法。创新：PrEP是第一个已被证明可有效降低MSM中HIV发病率的生物医学预防干预措施;但最佳实施需要同时进行行为干预，iPrEx研究中与HIV发病率相关的大量非依从性证明了这一点。拟议的研究将允许开发一个最佳的AC预防包，包括艾滋病毒预防的生物医学和行为相结合的方法。 公共卫生相关性：到目前为止，在美国和其他西方环境中，男男性行为者感染艾滋病毒的风险远远超过男性，在国际环境中，他们受到艾滋病毒的严重影响。抗逆转录病毒药物预防（AC）已被证明可以减少感染事件，但依从性一直不佳，阻碍了药物的充分益处。通过将循证行为干预与临床环境中的AC提供相结合，联合生物行为干预可能是减少MSM新发HIV感染的有效策略。

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.