The relationship between hepatitis C virus (HCV) genotype and HCV and human immunodeficiency virus (HIV) type 1 disease is not well defined. The present study analyzed data from a cohort of 207 HIV-1-infected and 126 HIV-1-uninfected children and adolescents with hemophilia who enrolled in the Hemophilia Growth and Development Study and were followed for 7 years. The mean HCV RNA level was higher in the participants in the HCV genotype 1 group than in the participants the HCV non-genotype 1 group, among both the HIV-1-infected (difference, +0.33 log(10) copies/mL; P=.038) and HIV-1-uninfected (difference, +0.59 log(10) copies/mL; P=.008) participants. Although HCV genotype was not associated with differences in HIV-1 RNA level, a significantly lower mean CD4(+) T cell count (difference, -127 cells/ microL; P=.026) and percentage of CD4(+) T cells (difference, -4.3%; P=.027) were observed in the participants in the HCV genotype 1 group, compared with those in the participants in the HCV non-genotype 1 group. In addition, the participants in the HCV genotype 1 group were at increased risk for progression to AIDS-related mortality (hazard ratio, 2.44; P=.037). The present study suggests that HCV infection and genotype may influence the natural history of HCV and HIV-1 disease.