ABSTRACT Alcohol misuse is prevalent among persons living with HIV (PLWH) and associated with poor outcomes including less engagement in HIV care, more severe liver disease, and increased age-related comorbidities. Prior research on the intersection of alcohol and HIV has been conducted in relatively small samples or in select groups whose results may not be generalizable to the overall population of PLWH. The Alcohol Research Consortium in HIV?Epidemiology Research Arm (ARCH-ERA) was formed to investigate short and long-term effects of alcohol on clinical outcomes in the CFAR Network of Integrated Clinical Systems (CNICS). CNICS is an 8-site national network that is large, geographically and racially diverse, gender representative cohort of >31,000 PLWH in care. Careful outcomes adjudication, a large diverse population, and systematic longitudinal assessments of patient reported alcohol use, drug use, mental health symptoms, adherence, cognition, and other outcomes enables a rigorous approach to key questions on HIV and alcohol that are highly responsive to NIH HIV priorities: 1) disparities in HIV treatment outcomes; 2) HIV-associated comorbidities, neurological complications and aging. Capitalizing on the resources and infrastructure of CNICS, we propose the following aims: To examine longitudinal relationships of alcohol use, co- morbid drug use, and mental health disorders on the HIV Care Continuum; to determine longitudinal relationships between alcohol and liver disease progression in the era of direct acting antiretrovirals for hepatitis C virus treatment on liver disease outcomes; and to determine the impact of alcohol use on age-related comorbidities among PLWH in care. ARCH-ERA will continue to generate new knowledge on the intersection of HIV and alcohol to inform future research and clinical care in the US and globally.