Occult hepatitis B and risk of reactivation following switch to non-hepatitis B virus-active antiretroviral therapy in people with HIV

Occult hepatitis B infection (OBI), defined by the persistence of replication-competent hepatitis B virus (HBV) DNA in the liver in the absence of detectable hepatitis B surface antigen (HBsAg), represents a clinically relevant condition among people with HIV (PWH). The long-term persistence of covalently closed circular DNA within hepatocytes provides the biological basis for potential HBV reactivation, particularly after discontinuations of HBV-active antiretrovirals. In recent years, the increasing use of tenofovir-sparing and lamivudine-sparing antiretroviral strategies, including dual and long-acting injectable regimens, has renewed concerns regarding this risk in individuals with serological evidence of prior exposure. We performed a narrative review to summarize current evidence on the epidemiology, biological mechanisms, and clinical relevance of OBI in PWH, with a focus on HBV reactivation following antiretroviral treatment (ART) switches. Evidence from case reports, observational cohorts, and randomized switch trials was examined. Available evidence indicates that HBV reactivation after withdrawal of HBV-active antiretrovirals in HBsAg-negative, antihepatitis B core antibody-positive PWH is a real but infrequent event. Reactivation appears to cluster in specific contexts, including advanced or poorly controlled HIV infection, absence of protective anti-HBs antibodies and a history of HBsAg loss during antiviral treatment. In contrast, in individuals with sustained HIV virological suppression, preserved CD4 ⁺ cell counts, and markers of effective immune control, the absolute risk of clinically significant reactivation is low. These findings support a risk-based approach to antiretroviral simplification incorporating HBV serological history, vaccination status, and postswitch monitoring, rather than uniform restrictions on treatment switches in PWH with resolved HBV infection.