HIV/HCV co-infected naïve patients (four females and six males) were evaluated for their response to the following treatment schedule: [(AZT 300 mg + 3TC 300 mg twice daily) + (fosamprenavir 700 mg twice daily) + (RTV 100 mg)]. CD3+/CD4+ T cells, interferon-gamma (INF-gamma) and interleukin-4 (IL-4) HCV-specific response, viral loads and transaminase levels were evaluated at time 0, and after 1, 3 and 6 months of therapy (T0, T1, T3, and T6 respectively). HIV-RNA, HCV-RNA and transaminases decreased at T1 and T3 compared with T0 (Mann-Whitney p <0.001, p <0.01 and p <0.01, respectively). At all time points, CD4+ and HCV-specific INF-gamma responses were higher (p <0.001; p <0.001), and IL-4 lower (p <0.01) after treatment. At T6, HCV-RNA was only negative in four out of ten patients whereas all had normal transaminase levels. These findings indicate that HAART treatment including fosamprenavir is able to activate a Th1 network in HIV/HCV co-infected patients. Moreover, these results, to be confirmed by larger cohort follow-up studies, suggest that this protease inhibitor could have potential implications for the treatment of chronic hepatitis C in HIV-positive patients.