Abstract Administrative Supplement Research Component 1 (RC1) Comprehensive Alcohol Research Center. Community and Interpersonal Stress, Alcohol, and Chronic Comorbidities among PLWH. Louisiana had the third highest rates of SARS-CoV-2 cases and the second highest deaths per capita in the country during the peak of the COVID-19 pandemic. The alarming high rate of mortality in New Orleans led to strict government issued mandates for social distancing, self-quarantine, and shelter-in-place measures adding challenges like unemployment, loss of social networks, fear, and decreased access to personally delivered healthcare to the most vulnerable individuals. These stressful factors negatively impact pre-existing symptoms of stress, anxiety, and depression and may have unwanted consequences that contribute to morbidity and mortality of vulnerable populations. Persons living with HIV (PLWH) have an excessively high rate of exposure to chronic and lifetime social stressors, that are linked to elevated rates of poorer mental health including depressive disorders, alcohol use disorders (AUD), and post-traumatic stress disorder (PTSD). Alcohol consumption tends to increase during times of duress and uncertainty, and alcohol is often misused to cope with stress, anxiety, and other uncomfortable emotions. Psychiatric comorbidities decrease adherence to antiretroviral therapy and increase risk for substance use that together may increase risk for comorbidities or negatively impact disease progression particularly in aging PLWH. Heightened psychosocial and physiological stress among PLWH is associated with poorer immune status, increased viral load over time, faster disease progression, and higher rates of mortality. Our overarching hypothesis is that PLWH with AUD experience greater psychobehavioral and biological consequences of the COVID-19 pandemic. This administrative supplement proposes studies within the scope of those proposed in Specific Aim 1 of RC1: To examine the impact of neighborhood and interpersonal stress on alcohol use and its associated comorbidities in PLWH. This aim tests the hypotheses that a) Contextual stressors will be associated with alcohol use as well as clinical comorbidities (e.g., mental health, cardiometabolic conditions, neurocognitive impairment, and frailty) and b) Alcohol use mediates the relation between stress and clinical comorbidities. We propose to obtain self-reported measures of stress, anxiety, depression, and alcohol use of PLWH and HIV seronegative subjects enrolled in our longitudinal New Orleans Alcohol Use in HIV (NOAH) study during the pandemic. Quantitative and qualitative data collected during the government mandated shelter-in-place and within 2 months of reopening of the city will be integrated with individual level demographic, clinical (including serological immunological evidence of exposure), behavioral (alcohol use), and disease-specific (HIV viral loads and CD4/CD8 counts) data to determine the impact ...