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

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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.