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Chronic hepatitis C (CHC) and end-stage liver disease are becoming an increasingly common cause of mortality in patients with congenital bleeding disorders, especially in the HIV-coinfected group. Combination of pegylated interferon (Peg-IFN) and ribavirin has recently become the treatment of choice for CHC. In this study, we evaluated the safety and efficacy of combination therapy with Peg-IFN plus ribavirin for the treatment of CHC in human immunodeficiency virus (HIV)- and HIV+ patients with congenital bleeding disorders. Between 2000 and 2004, 50 (18-68 years old) patients with CHC (19 HIV+) from two hemophilia centers were included in the study. They were treated with weekly subcutaneous administration of Peg-INF-alpha combined with 800-1,200 mg ribavirin daily, for 24-48 weeks depending on viral genotype. Response was evaluated at weeks 12, 24, 48 (end of treatment response) and 72 had sustained virological response). Overall, 22/50 patients (43.8%) had end of treatment response and 20/50 (40%) sustained virological response. HIV- patients responded similarly to the general population (58.1%), while HIV+ patients had very low response rates (10.5%). The high rate of discontinuation (36.9%) as a result of side effects contributed to the observed low response rate in the HIV+ group. The only factor strongly associated with sustained virological response in the HIV- patients was the reduction of HCV RNA at 12 weeks (p = 0.001). Patients with viral genotypes other than 1 had higher SVR rates, but this was not found to be statistically significant. Peg-INF plus ribavirin is safe for the treatment of CHC monoinfected patients with inherited bleeding disorders, with similar response rates to nonhemophiliacs. On the contrary, in HIV coinfected hemophilic patients under highly active antiretroviral therapy it is associated with severe toxicity and very poor sustained virological response rates. Careful evaluation and several considerations are needed before starting treatment in this population.

The antiviral drug ribavirin (1, beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) produced significant hematologic effects when administered to rhesus monkeys by intramuscular injection over 10 days in doses of 30 or 100 mg/kg/day. The monkeys developed dose-related progressive anemia and thrombocytosis associated with marrow erythroid hypoplasia and megakaryocyte hyperplasia. In addition, bone marrow examination revealed phagocytosis of erythroid elements by histiocytes; vacuolization of erythroid precursors, and to a lesser extent precursors of other cell types; and occasional erythroid precursors with megaloblastoid appearance. The alterations were transient and disappeared on discontinuation of the drug.