Ongoing risk behavior and the presence of HCV-RNA affect the hepatitis C virus (HCV)-Specific CD4(+) T cell response

The largest population of people at risk for HCV-infection is injecting drug users (DU). We hypothesize that recurrent exposure to HCV, by continuing risk behavior, influences the development of an HCV-specific T-cell response. Therefore, we studied the association between repeated exposure to and the height and focus of the HCV-specific T-cell response in HCV antibody-positive injecting DU (n=18) with ongoing risk behavior ('high-risk'), 9 with and 9 without detectable HCV-RNA), and 9 never-injecting DU ('low-risk', HCV-RNA+). Both total HCV-specific T-cell response, as well as the T-cell response against HCV nonstructural proteins, were significantly higher in injecting compared to never-injecting DU. Interestingly, the high-risk HCV-RNA¯ had no measurable CD4(+) T-cell response to Core protein, compared to detectable responses to Core in the HCV-RNA+ group. Thus, both ongoing risk behavior and presence of HCV-RNA affect the HCV-specific T-cell response in both magnitude and specificity, which may have implications for vaccine development.