Ten percent of individuals infected with HIV-1 infection are carriers of hepatitis B virus (HBV). Patients with HIV-1 infection have a higher risk of HBV-related cirrhosis than HIV-1-negative-HBV-infected individuals, and co-infection with both viruses has been shown to decrease survival in affected individuals. With the advent of effective anti-HIV therapy, liver disease and particularly HBV infection, has become a major cause of morbidity and mortality in HIV-1-HBV co-infected individuals. The immune response to HBV remains poorly characterized and with increasing recognition of the genetic variation of HBV, may indeed differ between HBV genotypes. This project includes the application of an overlapping peptide library designed to quantify HBV-specific T cell responses to all HBV proteins, in all HLA types and with infection of the major HBV genotypes (A-D). HBV-specific responses will be characterized in the peripheral and intra-hepatic compartments of HIV-HBV co-infected individuals prior to HBV-active HAART and over the following 12 months in a prospective study. These studies will identify new immunogenic epitopes associated with HBV clearance and/or worsening liver disease. The specific epitope and HLA association will be identified. Viral dynamic studies will be performed with combination anti-HBV therapy in HBV-infected and HIV-1-HBV co-infected individuals. The half lives of free virions and infected hepatocytes will be calculated in combination with the longitudinal measurement of HBV-specific T cell responses. These studies will allow the rational development of combination anti-HBV therapy or targeted immunomodulatory interventions, such as therapeutic vaccination, that may be necessary for successful treatment of HBV infection in the setting of HIV-1.
