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Background:  Ethanol consumption and HIV infection have both been associated with accelerated liver fibrosis in persons infected with hepatitis C virus (HCV), although the mechanisms of this are unknown. We hypothesized that ethanol and HIV both suppress HCV-specific immunity.

Methods:  We defined as “drinkers” (consumed ethanol within the last month) and “nondrinkers” (denied ethanol in the last year) 38 subjects with HCV (19 drinkers, 19 nondrinkers) and 68 with HIV/HCV (34 drinkers, 34 nondrinkers). All subjects denied injection drug use in the last year. Immune responses were studied with ELISpot for IFN-g, IL-10, and TNF-a against HCV proteins Core, NS3, and NS5, and Candida and tetanus. Responses were defined as ³ 10 spot forming cells (SFC)/10⁶ peripheral blood mononuclear cells (PBMC) after subtraction of background. Nonparametric statistical tests were performed.

Results:  There were no significant differences between HIV/HCV and HCV subjects in age, sex, race, HCV genotype, HCV viral load, and prior injection drug use; 72% of HIV/HCV subjects had CD4 > 300 and 69% had HIV viral load < 400 with no significant difference between drinkers and nondrinkers. HCV subjects were significantly more likely than HIV/HCV subjects to have IFN-g responses to Candida (90% vs 59%, p = 0.001), tetanus (60% vs 10%, p < 0.001), Core (24% vs 7%, p = 0.02), and NS5 (13% vs 0%, p = 0.005). IL-10 and TNF-a responses to HCV proteins and recall antigens were more similar between HCV and HIV/HCV groups; only IL-10 to Core (34% vs 18%, p = 0.05) and TNF-a to NS5 (58% vs 35%, p = 0.03) were significantly different. IFN-g responses to HCV proteins were not significantly different between HCV and HIV/HCV drinkers, while for HCV vs HIV/HCV nondrinkers, IFN-g responses were significantly higher for Core (26% vs 0%, p = 0.004), NS3 (16% vs 0%, p = 0.04), and NS5 (16% vs 0%, p = 0.04). IFN-g responses to Core, NS3, and tetanus were higher in HCV nondrinkers than drinkers, but higher in HIV/HCV drinkers compared to nondrinkers (significant Breslow Day test for heterogeneity). In comparison, ethanol did not seem to have an independent effect on either IL-10 or TNF-a responses except for TNFa to NS5.

Conclusions:  Antigen-specific IFN-g immune responses are more affected by HIV status than IL-10 or TNF-a responses in persons with chronic HCV infection. The effect of HIV on immune responses is more pronounced in nondrinkers than in drinkers. Future studies should examine the interactions of ethanol and HIV on HCV-specific immune responses.

Keywords: Hepatitis C virus; Immune response; Ethanol