Coinfection with hepatitis C virus and HIV is not uncommon. Approximately 10 percent to 30 percent of HIV-infected individuals are also infected with HCV. Many natural history studies have found that those with coinfection have more significant, and more rapidly progressive, liver disease than HCV-infected individuals who are HIV-negative. While the pathogenesis of HCV liver disease is not well understood, many believe that the more advanced liver disease seen in those with coinfection is due to HIV-related immune deficiency.
The specific aims of this proposals are as follows:
Aim 1 : To determine serum HCV RNA levels and quasispecies complexity and diversity in HCV-infected patients with and without HCV coinfection. This study will test the hypothesis that those with coinfection have higher HCV viremia and lower quasispecies complexity and diversity than those who are HIV-negative.
Aim 2 : To determine intrahepatic HCV RNA by in situ assay in HCV-infected patients with and without HIV coinfection. This study will utilize an in situ assay for genomic and replicative HCV RNA to test the hypotheses that intrahepatic HCV replication is increased in those with HIV and correlates with liver disease severity. It will also test the hypothesis that both HCV replication and liver disease are increased in those with more advanced HIV-related immune suppression.
Aim 3 : To determine the effect of HAART on HCV viremia, quasispecies complexity and diversity, intrahepatic HCV replication, and the immune response to HCV. HIV infected patients who are to be treated with HAART will undergo liver biopsy for measurement of intrahepatic HCV replication both before and 12 months after initiating HAART. Other pre- and post-HAART measurements will include HCV viremia, HCV quasispecies complexity and diversity, an increase in intrahepatic staining for CD4 and CD8 cells, and an increase in peripheral lymphoproliferative responses.
