Molecular characterization of occult and overt hepatitis B (HBV) infection in an HIV-infected person with reactivation of HBV after antiretroviral treatment interruption

Occult HBV infection is characterized by the absence of surface antigenemia and the presence of potentially infectious hepatitis B virus (HBV)-DNA present in liver, serum, or both. Reactivation of chronic HBV infection in the presence of the HBV surface antigen (HBsAg) is a well-known complication in immunocompromised individuals under cytotoxic chemotherapy or in HIV-infected individuals when nucleos(t)ide analogs effective against HIV/HBV are discontinued. However, little is known on the possibility of such a complication in HIV-infected persons with HBV-core antibody (anti-HBc) as the sole serological marker of past HBV infection. Here we report the case of one HIV-infected, anti-HBc-positive individual who showed a severe reactivation of HBV after the interruption of antiretroviral therapy (ART). Analysis of the plasma samples revealed HBV-DNaemia, albeit at very low levels in the latent phase, while the HBV-DNA level was highly increased during the overt phase that corresponded to the period of ART interruption, decreasing dramatically after the subsequent introduction of tenofovir-based ART. Molecular analysis of HBV in the two phases showed that overt HBV infection was due to reactivation of the occult HBV rather than to reinfection. Our case underlines the possibility that occult HBV infection may still have the potential to be severely reactivated in HIV-infected individuals, particularly when antiretroviral treatment is discontinued.