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Prior to the advent of safe and highly effective hepatitis C virus (HCV) treatment, patients with human immunodeficiency virus (HIV)/HCV co-infection were referred to as a ‘special’ population. This definition was based on more rapid HCV disease progression in the presence of HIV co-infection, limited effectiveness of interferon-based HCV treatment and potential drug interactions between medications used to treat HIV and those to treat HCV infection. Although the availability of interferon-free, oral direct-acting antivirals (DAAs) has dramatically increased the effectiveness of HCV treatment in patients with HIV co-infection, this population still warrants special consideration. Specific issues for the treatment of patients with HIV/HCV co-infection in the era of oral DAAs include a high HCV disease burden with ongoing HCV infection and re-infection following successful treatment, frequent drug interactions that must be carefully evaluated and unanswered questions on the role of shorter HCV treatment durations.