The magnitude and breadth of hepatitis C virus–specific CD8+T cells depend on absolute CD4+T-cell count in individuals coinfected with HIV-1

CD8+T-cell responses are an essential antiviral host defense in persistent viral infections, and their sustained effectiveness is thought to be critically dependent on CD4+T-helper cells. To determine the relationship between HIV-1–induced CD4+T-cell depletion and hepatitis C virus (HCV)–specific CD8+T-cell responses during viral persistence, we studied 103 persons positive for HCV, 74 coinfected with HIV-1. CD8+T-cell responses to the entire HCV polyprotein were determined by using an interferon-γ enzyme-linked immunospot (ELISpot) assay. Although HIV-1 infection by itself was not associated with a diminished HCV-specific response, HIV-1–associated CD4+depletion was associated with significantly lower HCV-specific CD8+T cells (R = 0.48, P< .0001). In contrast, declining CD4+counts over the same range were not associated with diminished Epstein-Barr virus (EBV)– (R = 0.19, P= .31) or HIV-1–specific (R = –0.13, P= .60) CD8+T-cell responses in persons infected with all viruses. These data indicate that frequencies of circulating HCV-specific CD8+T-cell responses are sensitive to absolute CD4+T-cell counts and provide a possible explanation for the accelerated HCV disease course in persons coinfected with HIV-1 and HCV.