Impact of human immunodeficiency virus on hepatitis B-specific immune responses

Prior infection with hepatitis B virus (HBV) is a common occurrence in HIV infected subjects and an increasing cause of morbidity and mortality. The CD8 T cell response is crucial for the long-term control of the virus in patients resolving acute hepatitis B. I first examined the effect of HIV related immunodepletion on HBV-specific immune responses in patients who resolved HBV. A cross-sectional study showed a reduction in HBV-specific CD8 responses in HBV immune patients with HIV infection compared to those without. Longitudinal study of a subgroup of patients examined whether this attrition could be reversed by effective antiretroviral therapy. The introduction of highly active antiretroviral therapy (HAART) resulted in recovery of some HBV-specific CD8 and CD4 responses, in association with restoration of CD4 counts. These data provided a mechanism for the observed impairment of HBV control in the setting of HIV infection and support the ability of HAART to reconstitute functionally active responses. I also studied the HBV-specific cellular immune responses in HIV negative patients who resolved acute hepatitis B without symptoms, a group which has never been studied immunologically, but represents a significant proportion of hepatitis cases acquired in adulthood. In the last chapter I focused on the chronic hepatitis B carriers co-infected with HIV and the impact of HIV and HBV treatment. I showed that reconstitution of some HBV-specific T cell responses can also occur in HIV-positive patients after a reduction in HBV load. This potential to recover T cell responses provides support for the addition of anti-HBV therapy in the treatment of co-infected patients