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，副作用的降低和消除障碍 遵守抗逆转录病毒预防前预防（PREP）。评估这些改进 由于样本量要求，严格的资格标准和 评估仅限于主动比较器。应对这些挑战已使新颖的分析 方法越来越必要。拟议的研究将使用尖端的定量方法 通过结合各种信息来源来评估新的准备组合。来自艾滋病毒的数据 预防试验网络083和IPREX（预防预防倡议）试验将用于 将长效注射可注射的cabotegravir准备与与男人发生性关系的男人的安慰剂进行比较 变性妇女。结果将对长效注射的功效提供可靠的估计 Cabotegravir代替直接进行的直接随机比较。接下来，来自 语音（控制流行病的阴道和口服干预措施）将与受试者整合 通过统计和机械建模来评估预期功效的物质专家知识 替诺福韦的阿拉芬酰胺和恩曲他滨每日口服妇女的口服准备。结果 第二个分析可以有助于计划在Cisgender中的替诺福韦alafenamide的随机试验 妇女（例如，评估计划的试验是否可能无法在以前证明疗效 观察到的依从性模式）。最后，灵活的分析工具应用了使用的定量方法 拟议的研究将通过开源软件开发并免费提供。 这些工具的提供将减少未来应用的障碍。该提议的科学结果 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。候选人将受益于强大的指导和艾滋病毒的额外培训 流行病学，机理建模，半参数理论和指导发展作为一种 独立科学家。通过其他定量方法培训，候选人将是独特的 准备共同使用统计和机械建模来带来特定场的优势来解决 这两个领域都无法自行解决的缺陷。培训和研究完成 这个指导的发展奖的目标将使候选人处于艾滋病毒的最前沿 流行病学和方法论研究，并准备候选人成为独立的 研究员。