T-Cell Profiles in HBV Functional Cure and People Living With HIV: Known Knowns, Known Unknowns, and Unknown Unknowns.

PURPOSE OF REVIEW: HIV further complicates the already complex clinical course of chronic HBV infection. Here we present a personal view of the current state of HBV-specific T-cell immunology and key questions about how T-cell immunity is altered during HBV/HIV co-infection. RECENT FINDINGS: While HIV usually exacerbates liver disease and increases mortality, higher rates of HBV functional cure – defined as HBsAg loss – are observed after initiation of antiretroviral therapy compared to HBV monoinfection. This creates an exciting opportunity to observe the mechanisms of HBV control during treatment induced immune reconstitution in real time. We discuss how HIV-induced immune CD4 depletion and altered CD8 T-cell differentiation might intersect in distinct ways with the complex natural history of chronic hepatitis B and the different scenarios of co-infection. We also propose how innovative T-cell studies applied to well-designed prospective co-infection cohorts could dramatically enhance our insights into the mechanisms of HBV control and persistence and inform development of novel immunotherapies for people living with HBV and HIV.