The effect of anti-human immunodeficiency virus (HIV) treatment on hepatitis C virus (HCV) RNA levels in HIV-HCV-coinfected persons is uncertain. Although it is commonly believed that, with the initiation of HIV treatment, there may be an initial increase followed by a gradual decrease of HCV RNA levels to lower than those at pretreatment, the published studies evaluating this are of small and heterogeneous populations, are limited in follow-up, and have conflicting results. A prospective clinical trial of sufficient size and duration may help clarify this issue. This may be clinically relevant, because lower HCV RNA levels are a predictive factor for favorable response to HCV antiviral therapy.