Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) coinfection is common in hemophiliacs and injection drug users. To assess the interaction between HCV load and HIV-1 disease progression, we examined 207 HIV-1/HCV—coinfected patients. Patients were followed prospectively for ∼7 years, and annual measurements of CD4+ cell counts and HCV and HIV-1 loads were obtained. Survival analysis was used to define the independent effects of HCV load on HIV-1 progression. After controlling for CD4+ cell count and HIV-1 RNA level, every 10-fold increase in baseline HCV RNA was associated with a relative risk (RR) for clinical progression to acquired immunodeficiency syndrome (AIDS) of 1.66 (95% confidence interval CI, 1.10–2.51; P = .016) and an RR for AIDS-related mortality of 1.54 (95% CI, 1.03–2.30; P = .036). These findings emphasize the need for further research regarding the use of HIV-1— and HCV-specific therapy in coinfected individuals.