CD4+ T cell-dependent reduction in hepatitis C virus-specific humoral immune responses after HIV infection.

Abstract

Human immunodeficiency virus (HIV) infection adversely affects all stages of hepatitis C virus (HCV) infection, leading to increased rates of viral persistence, higher levels of HCV viremia, and accelerated progression of HCV-related liver disease. These disease interactions may result in part from impairment of B cell function, which is CD4(+) T cell dependent. To determine the effect of HIV infection on B cell function, we compared HCV antibody levels and specificities in 29 HCV-infected persons before and after they acquired HIV and assessed the temporal correlation of these changes with overall CD4(+) T lymphocyte counts. The pre-HIV infection HCV antibody titer was a predictor of the subsequent titer for all antigens, and decreasing CD4(+) T cell numbers was strongly associated with a decrease in anti-HCV titers for several antigens. CD4(+) T cells counts of <500 cells/mm(3) were significantly associated with lower HCV antibody end-point titers. Higher HCV end-point titers were associated with fewer years from HIV infection and, for Core antigen, current drug use. HCV-specific antibody production is impaired by HIV infection, and loss of antibody production depends on CD4(+) T cell depletion. However, the decrease in titers is less significant in those who continue to actively inject drugs.