PROJECT SUMMARY / ABSTRACT The US opioid overdose epidemic has been accompanied by an increase in human immunodeficiency (HIV) among persons who inject drugs. The co-occurrence of HIV and opioid use disorder (OUD) suggests that a comprehensive approach to OUD and its infectious complications has the potential to improve outcomes. HIV pre-exposure prophylaxis (PrEP) and medication for opioid use disorder (MOUD) are evidence-based approaches that are recommended for persons who inject drugs. Unfortunately, these measures have not been widely adopted in real-world settings or accessed by persons at-risk. Foundation for the Proposal: The CHORUS intervention (Comprehensive HIV and Opioid use disorder Response to the Unaddressed Syndemic) is informed by preliminary research, including: (a) quantitative and qualitative research with persons with substance use disorder, (b) a randomized controlled trial of a peer-delivered motivational intervention demonstrating effectiveness in reducing heroin and/or cocaine use, and (c) preliminary studies demonstrating the feasibility and acceptability of peer-delivered motivational interventions in non-traditional settings. During the CHORUS pilot phase, we uncovered that PrEP was initiated late in the intervention. Therefore, we are attempting to accelerate PrEP initiation by providing HIV self-testing (CHORUS +) at baseline. The CHORUS+ intervention includes HIV self-testing, rapid initiation of PrEP and MOUD, and a 6-month peer recovery coach to support adherence to these medications. Conceptual Model: CHORUS+ is a theory-based, peer-delivered, mobile phone-supported intervention focused on enhancing uptake and adherence to HIV PrEP (primary outcome), and receipt of MOUD (secondary outcome) among persons who inject opioids. CHORUS+ aims to improve behavioral skills and self-efficacy while addressing structural barriers. Summary: The current proposal seeks to determine the efficacy of a novel intervention to increase the uptake of evidence-based measures to prevent HIV and treat opioid use disorder. We will compare the CHORUS+ intervention to usual care (passive referral) among persons who inject opioids (aim 1). In addition, we will examine study implementation to facilitate potential future dissemination using a mixed-methods process evaluation of CHORUS+ (aim 2). The study will be performed at Boston Medical Center’s Faster Paths clinic, a low-barrier substance use disorder bridge clinic, and through Victory Programs, which utilizes a mobile outreach van. The proposed intervention will recruit from non-traditional settings in order to reach participants who might not be comfortable in office- based clinics. This project specifically addresses NIDA’s mission of developing effective socio-behavioral interventions to increase uptake of HIV prevention strategies, and accelerating the adoption of evidence-based interventions to address substance use and its infectious complications.