Immune responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus infected and HIV-1 coinfected patients

Objective: To characterize immune phenotype and function in hepatitis C virus (HCV) infection in the presence and absence of HIV-1 infection. Design: Cross-sectional comparison among controls (group A), patients with HCV infection (group B), HCV-HIV-1 coinfected patients (group C), coinfected patients receiving treatment for HIV-1 (group D), and untreated HIV-1 infected patients (group E). Methods: Flow cytometric analysis for lymphocyte phenotypes, lymphocyte proliferation and cytokine production by ELISPOT. Results: HCV infected patients tended to have an increased percentage of activated (CD38, HLA-DR) CD8 cells (group A, 2 ±1.4%; group B, 6 ± 3.9%; P= 0.08). Proliferative responses to non-HCV antigens were comparable in group A and group B subjects. A greater proportion of group B patients had stimulation indices (SI) > 3 to the HCV protein NS3 compared to group C and D patients (67%, 0%, and 11% respectively; P< 0.003), but only two patients in group B had SI ≥ 5. The SI to NS3 was significantJy higher in group B patients [median, 4; interquartile range (IQR), 3-9) than in group C (median, 2; IQR, 1-3; P< 0.04) or group D (median, 1; IQR, 1-4; P < 0.009) patients. Plasma HCV RNA levels correlated directly with alanine amino-transferase levels (p, 0.52; P < 0.05) and inversely with the number of CD4 lymphocytes (p, -0.55; P < 0.009) and proliferation to NS3 (p, -0.55; P < 0.009). Conclusions: Lymphocytes of HCV infected patients show weak proliferative responses to HCV antigens while responses to other antigens are preserved. Infection with HIV-1 potentiates this deficiency. Poor CD4 T cell responses to HCV are associated with and may determine the failure to control HCV propagation. (C) 2000 Lippincott Williams and Wilkins.