Framed by the multiphase optimization strategy (MOST), and building on our recent preliminary studies, we are requesting 5 years of support to conduct an optimization trial among people who inject drugs (PWID) and newly enrolled on medication for opioid use disorder (MOUD). The goal is to assess the performance of four intervention components (Attention, Executive Functioning, Memory, and Information Processing) aimed at enhancing the ability of PWID on MOUD to process and utilize evidence-based HIV prevention content, leading to improvements in Pre-Exposure Prophylaxis (PrEP) adherence and HIV risk reduction. Existing evidence-based interventions require participants to have at least moderate levels of cognitive functioning but do not acknowledge or accommodate participants with cognitive dysfunction. This is a crucial weakness as cognitive dysfunction is a common feature among PWID, and one that can directly impede their ability to process and utilize intervention content. In fact, our recent studies comparing objective and self-report cognitive assessments (e.g., NIH toolbox) show that ~67% of PWID experience substantial levels of cognitive dysfunction across tasks involving attention, executive function, memory, and information processing that, in turn, disrupt the expected intervention outcomes (e.g., medication adherence, HIV risk reduction). Our recent work also suggests that PWID newly enrolled on MOUD would benefit from an intervention approach that incorporates ‘compensatory strategies’ to accommodate their cognitive dysfunction. A number of well-established compensatory strategies have been successfully applied to other patient populations (e.g., traumatic brain injury, ADHD, Alzheimer’s/dementia) and have been identified by our team as promising intervention components that could enhance evidence-based PrEP-focused primary HIV prevention approaches targeting PWID on MOUD. To date, however, no studies have examined the potential impact and cost of incorporating such intervention components, either individually or in various combinations, in terms of enhancing PWID’s ability to process and utilize HIV prevention content. This innovative trial will be the first to use the MOST framework to optimize an evidence-based HIV prevention approach by compensating for cognitive features that are characteristic of PWID on MOUD, and maximizing PrEP adherence outcomes within real world budget constraints.

A multiphase optimization strategy (MOST) will be used to conduct an optimization trial among people who inject drugs (PWID) and are newly enrolled on medication for opioid use disorder (MOUD). We will assess the impact and cost of four promising intervention components (Attention, Executive Functioning, Memory, and Information Processing). The components are designed to accommodate cognitive dysfunction such that participants can better process and utilize intervention content, thus leading to enhanced PrEP adherence and HIV risk reduction.