Data from large observational cohort studies of people with HIV in the US and Europe have yielded equivocal findings on the relationship between substance abuse and progression of HIV. A key problem is the inconsistent and varied definition of substance abuse employed in the analyses. To address such limitations, this research proposal will use an approach to substance abuse exposure measurement involving novel statistical techniques to better capture trajectories of substance abuse over time and to assess their effects on relevant clinical and public health HIV outcomes. First, the patterns of substance abuse (alcohol and non-medically prescribed psychoactive drugs) over time among HIV positive and negative adults will be analyzed to characterize their distinct trajectory classes. Then, among those with HIV, this study will examine the role of the substance abuse patterns in determining several outcomes important to the clinical and public health management of HIV in an aging, adult population: progression of the disease, adherence to HIV medication, and mortality. Using data accumulated from a large, multi-site prospective cohort study, the Veteran's Aging Cohort Study (VACS), we aim to provide a better understanding of the influence of substance use and abuse in HIV treatment and care. Analyses will also explore how broader, contextual characteristics such as perceived accessibility of one's healthcare provider and neighborhood-level disadvantage, inter-relate with the patterns of substance abuse and HIV health outcomes. Results from this study may assist clinicians in treatment decisions about their substance abusing HIV positive patients and help identify those at greatest risk for poor health outcomes. Findings may also suggest areas for more targeted public health preventive- and treatment-interventions for HIV positive, substance abusing populations and help to inform drug, alcohol, mental health, and HIV/AIDS treatment guidelines. ? ? ?