Combining sources of information to improve HIV pre-exposure prophylaxis

结合信息来源改善艾滋病毒暴露前预防

• 批准号: 10700193
• 负责人: Paul Nicholas Zivich
• 金额: $ 13.63万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-28 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700193
• 关键词: AIDS prevention; Acceleration; Address; Adherence; Adoption; Anti-Retroviral Agents; Award; Clinical Trials; Communicable Diseases; Computer software; Data; Development; Effectiveness; Eligibility Determination; Epidemiologic Methods; Epidemiology; Evaluation; Formulation; Fumarates; Future; Goals; HIV; HIV Infections; HIV prevention trials network; Injectable; Intervention; Knowledge; Learning; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Modeling; Oral; Participant; Pattern; Physicians; Placebos; Public Health; Randomized; Research; Research Methodology; Research Personnel; Sample Size; Scientist; Software Tools; Source; Tenofovir; Training; Vagina; active comparator; analytical tool; arm; career; cis-female; data fusion; data integration; efficacy evaluation; emtricitabine; epidemic response; flexibility; improved; inclusion criteria; interest; men who have sex with men; multiple data sources; novel; novel drug combination; open source; placebo controlled trial; pre-exposure prophylaxis; randomized trial; recruit; semiparametric; side effect; theories; tool; transgender women; treatment comparison; trial planning

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.

项目摘要 艾滋病毒预防需要提高有效性、减少副作用和消除障碍 抗逆转录病毒暴露前预防（PrEP）。对这些改进的评价 由于样本量要求、严格的合格标准和 评估仅限于活性对照药物。应对这些挑战使新的分析 方法越来越有必要。拟议中的研究将使用尖端的定量方法 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 在男男性行为者中比较长效注射用cabotegravir PrEP与安慰剂， 变性女性结果将提供一个可靠的估计的疗效长效注射剂 cabotegravir代替直接随机比较，这是不快。接下来，来自 VOICE（阴道和口腔干预控制流行病）试验将与受试者整合- 通过统计和机械建模来评估预期疗效的专家知识 替诺福韦艾拉酚胺和恩曲他滨每日口服PrEP在顺性别女性中的应用。结果从这个 第二次分析可以帮助规划替诺福韦艾拉酚胺在顺性别患者中的随机试验 女性（例如，评估计划中的试验是否可能无法证明先前试验的有效性 观察到的粘附模式）。最后，灵活的分析工具，以应用定量方法， 拟议的研究将通过开放源码软件进行开发和免费提供。 提供这些工具将减少未来应用的障碍。该提案的科学成果 将加速和加强我们如何从随机试验中学习， 预防艾滋病毒。候选人将受益于强有力的辅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，并指导发展作为一个 独立科学家通过额外的定量方法培训，候选人将是独一无二的 准备联合使用统计和机械建模，以发挥特定领域的优势， 这两个领域都无法单独解决的缺陷。完成培训和研究 这一指导性发展奖的目的将使候选人站在艾滋病毒的最前沿， 流行病学和方法学研究，并准备候选人成为一个独立的 研究员