CD4+ T-Cell–Dependent Reduction in Hepatitis C Virus–Specific Neutralizing Antibody Responses After Coinfection With Human Immunodeficiency Virus

Background. Human immunodeficiency virus (HIV) infection leads to lower rates of hepatitis C virus (HCV) clearance after acute infection, higher HCV viremia, and accelerated progression of HCV-related fibrosis. The mechanisms underlying this acceleration of HCV progression by HIV are poorly understood, but HIV-induced dysfunction in the anti-HCV humoral immune response may play a role. Methods. To define the effect of HIV coinfection on the anti-HCV antibody response, we measured anti-HCV envelope binding antibody titers, neutralizing antibody (nAb) titers, and nAb breadth of serum from HCV-infected subjects isolated longitudinally before and after incident HIV infection. Results. A significant reduction in HCV envelope-specific binding antibody and nAb titers was detected in subjects with CD4+ T-cell counts <350/mm3 after HIV infection, and subjects with CD4+ T-cell counts <200/mm3 also showed a reduction in nAb breadth. Subjects who maintained CD4+ T-cell counts ≥350/mm3 displayed little to no decline in antibody levels. Conclusions. Depletion of CD4+ T cells by HIV infection results in a global decline in the anti-HCV envelope antibody response, including binding antibody titers, nAb titers, and nAb breadth.