Combining sources of information to improve HIV pre-exposure prophylaxis

项目总结 艾滋病毒预防需要提高有效性，减少副作用，消除障碍 坚持进行抗逆转录病毒暴露前预防(PrEP)。对这些改进的评估 由于样本量要求、严格的资格标准以及 评估仅限于积极的比较者。应对这些挑战使新奇的分析 方法越来越有必要。拟议的研究将使用尖端的量化方法。 通过结合不同的信息来源来评估新的PrEP组合。来自HIV的数据 预防试验网络083和Iprex(暴露前预防倡议)试验将用于 在与男性发生性关系的男性中比较长效可注射卡波替格韦PrEP与安慰剂 变性女性。结果将为长效注射剂的疗效提供可靠的估计。 卡替格列韦代替直接随机比较，后者尚未公布。接下来，来自 VOICE(控制疫情的阴道和口腔干预)试验将与受试者整合- 通过统计和机械建模的物质专家知识来评估预期的疗效 顺性妇女每日口服替诺福韦、阿拉芬胺和恩曲他滨的PrEP。由此产生的结果 二次分析有助于规划替诺福韦丙氨酰胺治疗顺性反应的随机试验 妇女(例如，评估计划中的试验是否很可能无法在以前的 观察到的粘连模式)。最后，使用灵活的分析工具来应用 拟议的研究将通过开放源码软件开发并免费提供。 提供这些工具将减少未来应用的障碍。这项提议的科学成果 将加速和加强我们如何从随机试验中学习，并在 预防艾滋病毒。候选人将受益于强有力的指导和艾滋病毒方面的额外培训 流行病学、机械建模、半参数理论和指导发展 独立科学家。通过额外的量化方法培训，候选人将是独一无二的 准备联合使用统计和机械建模，以解决特定领域的优势 两个领域都不能轻易解决的不足之处。完成培训和研究 这个辅导性发展奖的目标将使候选人处于艾滋病毒的前沿 流行病学和方法学研究，并为候选人成为独立的 研究员。

PROJECT SUMMARY HIV prevention requires improvements in effectiveness, reduction of side-effects, and removing barriers to adherence for antiretroviral pre-exposure prophylaxis (PrEP). Evaluation of these improvements through randomized trials remains difficult due to sample size requirements, strict eligibility criteria, and assessments limited to active comparators. Addressing these challenges has made novel analytical approaches increasingly necessary. The proposed research will use cutting-edge quantitative methods to evaluate new PrEP combinations by combining diverse sources of information. Data from the HIV Prevention Trials Network 083 and iPrEx (Preexposure Prophylaxis Initiative) trials will be used to compare long-acting injectable cabotegravir PrEP to placebo among men who have sex with men and transgender women. Results will provide a reliable estimate of the efficacy of long-acting injectable cabotegravir in lieu of direct randomized comparisons, which are not forthcoming. Next, data from the VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial will be integrated with subject- matter expert knowledge through statistical and mechanistic modeling to evaluate the expected efficacy of tenofovir alafenamide and emtricitabine daily oral PrEP among cisgender women. Results from this second analysis can aid in the planning of randomized trials of tenofovir alafenamide in cisgender women (e.g., assess whether a planned trial would likely fail to demonstrate efficacy under previously observed adherence patterns). Finally, flexible analytic tools to apply the quantitative methods used in the proposed research will be developed and made freely available through open-source software. Provision of these tools will decrease barriers to future applications. Scientific results from this proposal will accelerate and strengthen how we can learn from randomized trials and make strides in the prevention of HIV. The candidate will benefit from strong mentorship and additional training in HIV epidemiology, mechanistic modeling, semiparametric theory, and guided development as an independent scientist. Through additional quantitative methods training, the candidate will be uniquely prepared to jointly use statistical and mechanistic modeling to bring field-specific strengths to address deficiencies that neither field can easily address on its own. Completion of the training and research aims of this mentored developmental award will situate the candidate at the forefront of HIV epidemiology and methodological research and prepare the candidate to become to an independent researcher.