Optimizing Antiretroviral-Based Prevention by Enhancing PrEP Adherence in MSM

描述(申请人提供)：背景：在艾滋病毒流行30年后，在过去的几个月里，一种新的生物医学预防方法正在出现。抗逆转录病毒化学预防(AC)已被证明是有效的，当联合配方的替诺福韦-恩曲他滨(TDF/FTC)每天口服作为暴露前预防(PrEP)(Iprex研究)时，可保护男男性行为者(MSM)(Iprex研究)；对于南非高危妇女，当围术期使用1%替诺福韦阴道凝胶时(2)。然而，在这两项里程碑式的研究中，AC的疗效因不依从性而显著减弱。自疫情开始以来，MSM一直是，并将继续是美国和世界各地面临新感染风险的最大群体之一(3，4)。因此，为了使AC作为一种有效的公共卫生干预措施，必须开发出旨在优化依从性的文化定制计划。设计：这款R34将适应并试点测试一种干预措施，以最大限度地提高MSM患者的口服AC依从性，为未来的R01奠定基础，以测试生物医学和行为预防联合干预的效果。我们建议：1)进行形成性、定性的研究，以更好地了解人们对AC有效性的认知、AC使用的障碍和促进者，并了解背景变量，例如高风险MSM如何将AC融入他们关于伙伴选择的决策(即，在稳定的伙伴关系中使用还是与匿名伙伴使用)。因此，将对参与芬威健康中心Iprex或CDC PrEP研究的MSM进行重点小组研究，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)利用这些数据开发和公开试点PrEP依从性干预措施，该干预措施可与PrEP临床监测一起对高危MSM进行；以及3)对该PrEP包进行试点随机对照试验，与积极的、时间匹配的对照试验进行比较。根据用药事件监测系统(MEMS)的上限来衡量，主要结果将是依从性，次要结果将是与PrEP相关的性风险补偿减少。干预发展过程：拟议的项目遵循一种迭代的干预发展方法，首先进行形成性研究，然后公开试点干预并对其进行提炼，第三，进行试点随机对照试验。这将为全面试验测试管理PrEP的最佳方法和优化依从性奠定基础。创新：PREP是第一个被证明在降低MSM中艾滋病毒发病率方面有效的生物医学预防干预措施；但最佳实施将需要同时进行行为干预，Iprex研究中与艾滋病毒发病率相关的大量不遵守就证明了这一点。拟议的研究将允许开发最佳的AC预防方案，包括艾滋病毒预防的生物医学和行为方法相结合的方法。

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.