Non invasive liver fibrosis scores have been proposed as alternatives to liver biopsy in hepatitis C virus (HCV) -infected patients. We assessed the impact of antiviral treatment on non invasive serological markers of liver fibrosis in HIV-HCV co-infected patients who received 48-weeks of HCV treatment. In HIV-HCV co-infected patients, HCV clearance was associated with a significant reduction in non invasive fibrosis serological markers, which most likely reflect the histological improvement associated with sustained virologic response. We assessed the association between insulin resistance, liver fibrosis, and liver steatosis in HIV-HCV and HCV-infected patients. Insulin resistance was associated with liver fibrosis and steatosis in HCV mono-infected but not in HIV-HCV co-infected patients. Significant liver fibrosis was associated with insulin resistance independent of liver steatosis only in HCV mono-infected patients. We also assessed the impact of insulin resistance on the response to HCV therapy in HIV-HCV co-infected patients. A high HOMA-IR level was frequently found in HIV-HCV co-infected patients and was associated with a reduced sustained virologic response rate. Improving insulin sensitivity may be a useful adjunct to HCV therapy in HIV-HCV co-infected patients.