Characterization Of HCV-specific T Cell Responses During HAART In HIV/HCV Coinfected Patients

HCV and HIV-1 are often harbored within the same host by sharing routes of transmission. It is estimated that HIV/HCV co-infected subjects accounts for approximately 33% of all HIV-infected persons, which proportions are increased to 85～90% in injection drug users. After successful anti-retroviral therapy in co-infected patients, the mobility of AIDS-related opportunistic infections and tumors decreased, whereas HCV-related liver diseases have emerged as the most important cause of mortality, which hints that HAART and followed immunological reconstitution may contribute to liver injury, and then lead to end-stage liver diseases. Hepatitis C virus is noncytolytic and liver injury is thought to be immune mediated. We presume that HCV specific T cell responses are much lower in HIV/HCV coinfected persons because of impaired cellular immune function and HAART can restore this impaired immunological function. These changes during HAART may lead to liver injury, along with viral erasion. This mechanism may account for high proportion of liver failure emerged during HAART.To determine the mechanism mentioned above, we studied 10 persons positive for HCV, 20 coinfected with HIV-1. 13 coinfected persons treated with HAART were enrolled in a follow-up study. Here we investigated the magnitude of liver injury and the change patterns of HCV-specific response after HAART in HIV/HCV coinfected patients. Liver injury was represented by plasma level of alanine aminotransferase(ALT) and T cell response was measured by interferon-γELISPOT and lymphoproliferation. The relationship of the changes of liver injury and HCV-specific responses was analysed to determine wheather or not HCV-specific T cell response conduce to liver injury in HAART-treated HIV/HCV coinfected persons.We found that HCV-specific T cell responses in HIV/HCV coinfected patients were much lower than that in HCV monoinfected patients. A positive relationship of HCV-specific T cell responses and CD4 counts existed in HIV/HCV coinfected group. After effective antiretroviral therapy, HCV-specific responses recovered in the whole group, whereas the levels of ALT elevated only in HCVRNA positive subjects, which showed the same change tendency existed in ALT and T cell response. Futher analysis indicated that not only the recovry of breadth, but the changes of property(IFN-γsecreting or IL-10 secreting) of HCV-specific T cell responses may contribute to the elevation of ALT levels.These results indicated that HIV infection impaired the immune response to HCV and the occurrence and magnitude of liver injury correlated with the recovery of HCV-specific T cell responses after antiretroviral therapy. HCV-mediated immunopathological damage may be the leading cause in the liver injury during HAART, and play a key role in elevated incidence rate of end-stage liver diseases.