BACKGROUND: Functional B cell responses for both prevention and control of hepatitis B virus (HBV) infection remain poorly understood, including in the context of HBV/HIV coinfection.

METHODS: Here, we employed high-dimensional single-cell analysis to assess global and hepatitis B surface antigen-specific (HBsAg-specific) B cells in a longitudinal cohort of incident HBV from the Multicenter AIDS Cohort Study, with a subset of the cohort living with HIV-1.

RESULTS: We observed that prior HIV infection has negative consequences for B cell function in early post-acute HBV infection, including increased frequencies of atypical memory B cells and regulatory B cells, expression of the activation marker CD86 on multiple B cell subsets in chronic HBV (CHB), and restricted expansion of HBsAg-specific B cells. In contrast, in HBV monoinfection, we observed no changes in the global B cell population from prior to infection and robust expansion of HBsAg-specific B cells. These expanded antigen-specific B cells resembled class-switched intermediate and resting memory B cells, with activation phenotypes that may contribute to ongoing HBV control.

CONCLUSION: HIV infection has a significant impact on B cell responses to subsequent HBV infection that may promote development of CHB in HBV/HIV coinfection.