Optimizing evidence-based HIV prevention targeting people who inject drugs on PrEP

拟议的4年补充项目将把功能性磁共振成像（fMRI）纳入 最近资助的暴露前预防（PrEP）多阶段优化策略（MOST）试验- 对新登记接受阿片类药物治疗的注射毒品者（PWID）进行重点干预 使用障碍（MOUD）治疗（R 01 DA 055534; Copenhaver，PI）。科学的前提是 补充直接建立在父母补助金中总结的证据上-认知功能障碍是 在PWID中很常见，如果不适当，则会破坏以PrEP为重点的艾滋病毒预防结果 很好神经成像成套测验将包括与认知功能障碍具体相关的任务 以及PrEP和MOUD结果以及在暴露于PrEP教育期间专门获取的数据 视频和休息状态下。基于我们之前在与母公司相同的MOUD诊所进行的工作 我们预计，约80%的入组母试验的个体将对以下项目感兴趣并有资格 功能磁共振扫描因此，我们预计在4年内扫描约200人， 目的：（1）进入PrEP的个体中认知功能障碍的脑机制- 集中干预。在fMRI扫描期间，参与者将完成特定的认知功能任务， 与母试验中测试的补偿性干预成分的相关性（即，验证任务 认知/执行功能、注意力、记忆和信息处理）。将使用以下方法分析数据： 先进的、基于网络的方法（例如，独立成分分析（Independent Component Analysis） PWID患者认知功能障碍的神经过程的综合表征 MOUD和PrEP，以及（2）识别回归风险行为的预测性神经标志物（即，准备和 MOUD成果）。我们将使用一种可解释的、基于连接性的方法， 模型（CPM），以确定PrEP和MOUD结果的预测性神经标志物。拟议 补充工作将提供对临床个体差异因素的机械洞察， 具有多种高风险行为的个体（例如，无安全套性行为，共用针头）的情况， MOUD，并且是开发优化的、基于生物学的预防和 采取干预措施，打击目前的阿片类药物流行病。

The proposed 4-year Supplement project will incorporate functional magnetic resonance imaging (fMRI) into a recently funded multiphase optimization strategy (MOST) trial of a Pre-Exposure Prophylaxis (PrEP)- focused intervention for people who inject drugs (PWID) who are newly enrolled in medication for opioid use disorder (MOUD) treatment (R01DA055534; Copenhaver, PI). The scientific premise for this supplement builds directly on evidence summarized in the parent grant - that cognitive dysfunction is common among PWID and disrupts PrEP-focused HIV prevention outcomes, if not properly accommodated. The neuroimaging battery will include tasks of specific relevance to cognitive dysfunction and to PrEP and MOUD outcomes as well as data specifically acquired during exposure to PrEP educational videos and during resting state. Based on our prior work conducted in the same MOUD clinics as the parent trial, we anticipate that ~80% of individuals enrolled in the parent trial will be interested in and eligible for fMRI scanning. Thus, we anticipate scanning approximately 200 individuals over 4-years, with the following aims: (1) Specifying brain-based mechanisms of cognitive dysfunction among individuals entering PrEP- focused intervention. During fMRI scanning, participants will complete cognitive function tasks with specific relevance to compensatory intervention components being tested in the parent trial (i.e., validated tasks of cognitive/executive function,, attention, memory, and information processing). Data will be analyzed using advanced, network-based approaches (e.g., independent component analysis) to provide the first ever comprehensive characterization of neural processes subserving cognitive dysfunction among PWID entering MOUD and PrEP, and (2) Identifying predictive neuromarkers of return to risk behaviors (i.e., PrEP and MOUD outcomes). We will use an interpretable, connectivity-based approach, connectome-based predictive modeling (CPM), to identify predictive neuromarkers of PrEP and MOUD outcomes. The proposed supplemental work will provide mechanistic insight into clinical individual difference factors among individuals with multiple high-risk behaviors (e.g., condomless sex, needle sharing) among individuals in MOUD, and is an essential precursor to the development of optimized, biologically based, prevention and intervention efforts to combat the current opioid epidemic.