Coinfection by the blood borne pathogens hepatitis C virus (HCV) and HIV is extremely common in hemophiliacs and intravenous drug users. Although HCV infection is the leading cause of liver transplants in the United States, most infected individuals do not develop symptomatic liver disease. Although cohort studies of individuals coinfected with both HIV and HCV have shown that coinfection increases the risk of liver failure, it is not known how HCV coinfection affects the natural history of HIV-1 progression. We have therefore initiated an investigation to explore the interaction between these pathogens in a study of 207 HIV-infected and 121 uninfected hemophiliacs with HCV infection who were involved in 1989-90 in the Hemophilia Growth and Development Study. A total of 332 hemophiliacs had 1-8 repeated annual HCV RNA measurements between baseline and 7 years of follow-up. CD4+ cells and plasma HCV RNA was measured annually in all subjects, and plasma HIV RNA was measured annually in the HIV-infected subjects. HIV and HCV RNA levels were quantified using second generation Chiron bDNA assays. Not unexpectedly, we found that baseline HCV RNA was higher in HIV-infected children than in uninfected groups (p=0.0001). We have also observed significant correlations between baseline CD4+ cell number, HIV RNA and HCV RNA: higher absolute CD4 T cells were correlated with lower HCV RNA while higher HCV RNA was strongly correlated with high HIV viral load. We also found a significant association between HCV viral load and rate of progression to AIDS: after controlling for HIV RNA, CD4 + T cells, and antiviral therapy, for every 10-fold increase in baseline HCV RNA, there was a 1.60 increase in the relative hazard for progression to AIDS. We also observed that HCV clearance rates are significantly lower in children with HIV coinfection. This study demonstrates that HCV is an independent predictor of HIV clinical progression and suggests that therapeutic interventions to lower HCV viral load should be investigated in coinfected patients. Interactions Between HIV and HCV in Hemophiliacs