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Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients.A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin.The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy.There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.