PROJECT SUMMARY/ABSTRACT Effective antiretroviral therapy has increased the lifespan of people living with HIV (PLWH). Alcohol use, common among PLWH, plays an increasingly important role in the risk for and management of HIV-associated comorbidities. Unhealthy drinking can exacerbate two highly prevalent HIV-related comorbidities/co-occurring conditions, chronic pain and physical inactivity, which in turn, can intensify alcohol use and affect physical and mental function in PLWH. We propose the Boston Alcohol Research Collaboration on HIV/AIDS – Comorbidity Center (Boston ARCH CC) as an extension of our Boston Alcohol Research Collaboration on HIV/AIDS (ARCH) cohort launched in 2011 and renewed in 2016 with funding from NIAAA. In Boston ARCH CC we target in randomized trials these two modifiable conditions, pain and physical inactivity, that have a critical impact on a variety of other HIV-related comorbidities. Boston ARCH CC contains 4 integrated components that make unique contributions to our interdisciplinary approach: two randomized trials (Research Project Components), an Administrative Core (AC) that coordinates the P01, and a Biostatistics and Data Management (BDM) Core that supports the trials methodologically and provides data management and biostatistical expertise to them, and continues secondary analyses using extant Boston ARCH data. In Objective 1 we will conduct state-of-the-art e-health clinical trials research on scalable approaches to address the HIV-associated conditions chronic pain and physical inactivity in PLWH with unhealthy alcohol use. By recruiting, assessing, and intervening with participants outside of standard medical visits, through entirely online e-health procedures, our trials address unhealthy drinking in the care of complex HIV patients. In Objective 2 we will support secondary analyses of the existing Boston ARCH cohort, and provide support and mentoring to trainees and investigators accessing the cohort data. The nearly ten- year prospective Boston ARCH cohort enrolled PLWH with current or past substance use, and provides the basis for creating a program for early stage alcohol-HIV investigators interested in scientific questions related to pain, physical inactivity, and physical and mental functioning. To achieve the goal of addressing these two co-occurring conditions, we bring together multidisciplinary experts in fields including alcohol and HIV, public health, addiction medicine, clinical trials, psychology, pain, physical activity, ecological momentary assessment, functional status measurement, and research methods and services (biostatistics and data management). The integration across these fields provides a cohesive program where the whole is bigger than the sum of the parts, supporting investigators whose work can be rapidly translated to community-based population impact.