Background:  Injection drug use (IDU) accounts for >60% of current HIV/hepatitis C virus (HCV) infections in North America. Opiates have been shown to alter immune responses and may induce immune activation. Effects of opiate use on immune responses to HIV or HCV are not well characterized, but may have implications for disease progression.

Methods:  Enzyme-linked immunosorbent spot (ELISpot) assays measured interferon-gamma (IFN-g), interleukin (IL) -2, and tumor necrosis factor-alpha (TNF-a) secretion in response to HCV proteins core, NS3, and NS5, Candida, and HIV-1 whole protein in the following groups:  heroin IDU (HIV/HCV = 11, HCV = 6), methadone use (HIV/HCV = 19, HCV = 12), and nonusers (no heroin, methadone, cocaine, or alcohol in 6+ months; HIV/HCV = 57, HCV = 27). Sum-HCV = sum of core, NS3 and NS5 SFC. A panel of 24 cytokines and chemokines was measured on conditioned media. Nonparametric tests were used to compare groups.

Results:  IFN-γ and IL-2 HCV-specific responses in all HIV/HCV user groups were similar. In the HIV/HCV groups, heroin users had lower HIV IFN-g responses than methadone users (p <0.05) or nonusers (p <0.05). Conversely, HIV-specific IL-2 responses were similar with heroin compared to methadone users and nonusers. HCV nonusers had lower IFN-g responses to sum-HCV compared to HCV heroin users (p <0.01) and methadone users (p <0.04) while IL-2 HCV responses were similar. TNF-a secretion to all antigens was similar for HIV/HCV and HCV user groups. HIV/HCV heroin users had significantly lower IL-4, MDC, Eotaxin, IP10, MIG, and TARC levels in control media compared to HIV/HCV nonusers, while HIV/HCV methadone users had significantly lower IL-1a, IL-1b, and IL-6 levels than HIV/HCV nonusers. In contrast, there were no significant differences between HCV heroin or methadone users and nonusers in this panel. The effect of HIV alone was modest:  HIV/HCV nonusers had higher IFN-g to NS5 vs HCV nonusers (p <0.01), but all other IFN-γ HCV and IL-2 HCV responses were not significantly different compared to HCV nonusers. As expected, HIV/HCV nonusers also had lower responses to Candida than HCV subjects for IFN-g (p <0.03) and IL-2 (p <0.02).

Conclusions:  In subjects with HIV, ongoing opiate use has little effect on HCV-specific immune responses, either in terms of IFN-γ or IL-2 production, although it does diminish the HIV-specific response. Conversely, in those with HCV an effect of opiate use on IFN-γ responses was observed. This suggests that studies of HCV-specific immune responses in HIV/HCV do not have to account for ongoing opiate use as a cofactor in immunologic responses.