This proposal is an urgent competitive revision designed to supplement an existing NIH-funded study to assess the impact of the COVID-19 pandemic on alcohol and other drug use, and medication adherence that is critical for preventing HIV disease progression, among people living with HIV (PLWH). The COVID-19 pandemic has profoundly affected lives around the world. In addition to the effects of infection itself, to which PLWH may be more susceptible, COVID-19 has affected employment, access to healthcare, and very likely, the incidence and consequences of other health conditions, by limiting access to healthcare, and through the implementation of physical (social) distancing. PLWH may be at higher risk of consequences of social isolation, and those with addiction, unemployment and homelessness are at an even higher risk with restrictions that affect food availability, hygiene (e.g. handwashing), shelter, and other traditional supports now absent from the already fragile societal safety net. The over-arching goal of this proposal is to assess the impact of the COVID-19 pandemic and the effects of physical (social) distancing and other mitigation strategies (collectively termed “pandemic exposure”) on substance use (heavy alcohol use and/or other drug use including nonmedical prescription medication use) and HIV medication adherence among PLWH. Among an ongoing, well-characterized cohort of people living with HIV/AIDS (the existing Boston ARCH Cohort parent study), this project will: Aim 1: Determine prospective associations between pandemic exposure and changes in alcohol (and other drug) use (primarily) and HIV antiretroviral (ARV) medication nonadherence (secondarily). Aim 2: Identify associations between pandemic exposure and secondary stressors, specifically, food insecurity, loneliness, and pain interference (with activities); and associations between those stressors and changes in alcohol (and other drug) use and HIV ARV medication nonadherence. Aim 3: Determine who is most affected by the pandemic by examining moderators of the associations between pandemic exposure and changes in substance use and HIV ARV nonadherence. To achieve these aims, a supplemental COVID-19 specific assessment will be administered to participants at two time points (6 months apart). Baseline data on substance use, depression, and frailty, collected during pre-pandemic assessments as part of the parent study will be compared against data collected via supplemental COVID-specific assessments. Achieving this proposal’s aims is an important step to identifying modifiable targets for interventions to prevent increased substance use and HIV disease progression after an extreme event such as COVID-19.