Impact of HIV on Host-Virus Interactions during Early Hepatitis C Virus Infection

Background. Human immunodeficiency virus (HIV)may influence the outcome and natural history of hepatitis C virus (HCV) infection through an impact on acute HCV-specific T cell responses. Methods. Fifty-five HIV-positive males with acute HCV infection were identified; monoinfected individuals (n! 8) were used for peripheral blood mononuclear cell comparison. In 14 coinfected and 8 HCV-monoinfected patients, HCV-specific T cell responses against a range of HCV antigens were assessed using interferon (IFN)–" enzyme-linked immunospot (ELISpot) and proliferation assays. E1/E2 region genetic diversity and the selection pressure on the virus were measured in 8 coinfected patients by use of cloned sequences over time. Results. HCV persisted in 52 (95%) coinfected individuals. HCV/HIV coinfection significantly reduced IFN-" ELISpot responses versus those in HCV-monoinfected individuals, especially against nonstructural proteins (1/10 vs. 5/8;P!.008). In coinfected patients, increasedHCVgenetic diversity was observed between the first and subsequent time points, with no evidence for positive selection in the E1/E2 region sequenced. Conclusion. HIV coinfection is associatedwith increased rates ofHCVpersistence and a lack of critical CD4T cell responses, with no evidence of immune selection pressure during early HCV infection. Loss of key cellular immune responses against HCV during acute disease may contribute to the failure of early host control of HCV in HCV/HIV-coinfected patients