Abstract: The number of persons living with HIV (PLWH) continues to increase in the United States. Alcohol consumption is a significant barrier to both achieving the goal of ending the HIV epidemic and preventing comorbidities among PLWH, as it contributes to both HIV transmission and HIV-related complications. Recent advances in data capture systems such as mHealth devices, medical imaging, and high-throughput biotechnologies make large/complex research and clinical datasets available, including survey data, multi-omics data, electronic medical records, and/or other sources of reliable information related to engagement in care. This offers tremendous potential of applying “big” data to extract knowledge and insights regarding fundamental physiology, understand the mechanisms by which the pathogenic effects of biotic and abiotic factors are realized, and identify potential intervention targets. We propose to integrate the disparate data sources maintained by our partners and then utilize the big data to address research questions in treating HIV and alcohol-related morbidity and mortality. Specifically, we will pursue the following three aims: 1) Integrate the disparate data sources through standardization, harmonization, and merging; 2) Develop a web-based data sharing platform including virtual data sharing communities, data privacy protection, streamlined data approval and access, and tracking of ongoing research activities; 3) Provide statistical support to junior investigators to use the data repository for exploratory data analysis and proposal development. The proposed study will tap into disparate data sources, unleash the potential of data and information, accelerate knowledge discovery, advance data-powered health, and transform discovery to improve health outcomes for PLWH.