This proposal aims to understand the effects of HIV on the humoral immune response to hepatitis B by focusing on HBV-specific neutralizing antibodies (NAbs), B cell repertoires, and monoclonal antibodies that develop after acute hepatitis B infection or after treatment-induced control of infection. Innovative aspects of this project include: 1) The unique cohort with a large number of incident HBV infections with either spontaneous control or viral persistence in people living with and without HIV infection, as well as rare individuals with treatment-induced control of HBV, 2) The ability to detect NAb responses in plasma from human subjects, and 3) The ability to isolate HBsAg-specific B cells for ex vivo study. To date, such studies have not been possible, explaining why there is little information on NAb responses in HBV-infected humans. Results from this proposal will contribute to our understanding of the effects of HIV on the immune response to hepatitis B and could facilitate development of a functional cure for hepatitis B, the leading cause of cirrhosis and hepatocellular carcinoma worldwide.