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Hyperlipidemia is a recognized complication of HIV antiretroviral therapy. The interactions between HIV, hepatitis C virus (HCV), antiretroviral agents and lipids are not well understood.We evaluated the lipid data of patients receiving antiretroviral therapy at the Ottawa Hospital Immunodeficiency Clinic between January 1996 and June 2005 using a clinic database.A total of 357 HIV-mono-infected and 115 HIV/HCV-co-infected patients were evaluated. The mean changes in total cholesterol (mmol/l) from baseline to months 6 and 12 were 1.00 and 1.24 in HIV mono-infection, and 0.19 (P < 0.001) and 0.01 (P < 0.001) in HIV/HCV, respectively. Metabolic complications including hypercholesterolemia resulted in the interruption of HAART in HIV mono-infection (8%), but not in those with HIV/HCV (< 1%; P < 0.001). Eight per cent of HIV-mono-infected and no co-infected patients initiated lipid-lowering therapy while on their initial course of HAART (P < 0.001). Total cholesterol increased by 0.85 mmol/l in HIV/HCV-co-infected recipients of interferon-based HCV treatment achieving a sustained virological response (SVR), but did not change in those who did not achieve a SVR.HCV co-infection appears to confer a degree of protection from HAART-related lipid complications. The mechanism of this finding deserves evaluation. The implications of this observation for long-term cardiovascular disease risk remains a pressing issue.