Informing best practices for Substance-use Treatment with Real-world evidence for people with Opioid Use Disorder and HIV (STRONg) - Human immunodeficiency virus (HIV) and opioid use disorder (OUD) tend to be correlated and often co-occur with other substance use and mental health disorders. Treating OUD in PWH is critical to improve HIV outcomes and overall health. Buprenorphine, methadone, and naltrexone are efficacious medications for OUD (MOUD). In practice, adherence to MOUD is challenging. The impact of real-world MOUD use patterns is unknown, including the degree to which co-occurring substance use disorders (SUD) and mental health disorders, and and co-delivery of other SUD and mental health treatments (behavioral therapy and pharmacotherapy) modify the effect of MOUD among PWH. The Johns Hopkins HIV Clinical Cohort (JHHCC) is a cohort of PWH in Baltimore, Maryland. JHHCC participants consent to share their medical records and regularly self-report substance use and mental health symptoms. The clinic has a substance use treatment program that includes office-based buprenorphine and naltrexone. Chesapeake Regional Information System for our Patients (CRISP) is the regional health information exchange. We propose to comprehensively characterize OUD treatment, co-occurring substance use and mental health disorders, and HIV and overdose outcomes among PWH by linking JHHCC’s rich data on HIV outcomes, substance use, and mental health symptoms with CRISP’s area-wide records of controlled substance prescriptions, laboratory results, and hospitalizations and emergency room (ER) visits. In Aim 1, we will describe patterns of MOUD use among PWH with OUD as well as the associations between these patterns and co-occurring SUD or mental health disorders, and co-delivery of other SUD and mental health treatments. In Aim 2, we will estimate the effect of MOUD initiation and persistence on viral suppression, and explore whether this effect is modified by the aforementioned factors. In Aim 3, we will estimate the effect of MOUD use patterns on subsequent opioid overdose and all-cause mortality in PWH and again check for modification by co-occurring SUD or mental health disorders, and co-delivery of other services. These aims will improve our understanding of real-world use and effectiveness of MOUD therapy and the degree to which its effectiveness is modified or can be enhanced by comorbid conditions and medical care for mental health disorders. These insights are critical to integrating HIV and OUD care. The close relationship between OUD treatment and HIV care within the Bartlett Clinic underpins the proposed research and will facilitate the incorporation of our findings into clinical care.