Background:  Injection drug use (IDU) accounts for >60% of current HIV/hepatitis C virus (HCV) infections in North America, and ongoing alcohol and drug use are common. Effects of substance use on cellular immune responses are poorly understood.

Methods:  ELISpot assays measured interferon-g (IFN-g), interleukin-10 (IL-10), and tumor necrosis factor-a (TNF-a) secretion in response to HCV proteins core, NS3, and NS5, and Candida and tetanus in the following groups:  IDU in the past month (HIV/HCV = 16, HCV = 19), drinkers (alcohol in the past month; HIV/HCV = 34, HCV = 19), IDU/drinkers (HIV/HCV = 24, HCV = 14), and nonusers (no alcohol or IDU in at least 1 year; HIV/HCV = 34, HCV = 19). Responders had >10 spot forming cells (SFC)/10⁶ peripheral blood mononuclear cells (PBMC). Odds ratios (OR) for response to each cytokine/antigen were calculated, and combined OR (Cochran-Mantel-Haenszel) are shown.

Results:  Demographics were similar except HIV/HCV IDU had lower CD4⁺ cell counts than HIV/HCV nonusers. Each substance group was compared with nonusers, and an elevated OR indicates increased response compared to nonusers, controlling for HIV status. A (*) below indicates that Breslow Day test of homogeneity had p <0.05. Here, HIV/HCV IDU and drinker groups had higher IFN-g responses than HIV/HCV nonusers, while HCV nonusers had higher IFN-g immune responses than HCV IDU and drinkers so it was not appropriate to pool the OR.

Conclusions:  Alcohol and IDU appear to have a synergistic effect, augmenting TNF-a responses, and TNF-a is an important mediator of hepatocyte damage. HIV has a differential effect on IFN-g responses as compared to IL-10 or TNF-a responses.