Interferon-gamma with peginterferon alpha-2a and ribavirin in nonresponder patients with chronic hepatitis C (ANRS HC16 GAMMATRI)

Background and Aim Interferon-gamma-1b (IFN-?-1b) improves alpha interferon (IFN-a) inhibition of hepatitis C virus (HCV) replication in replicon system. We described virological response after addition of IFN-? to a combination of ribavirin/peginterferon (PEG-IFN)-a-2a or a-2b. Methods In this non-comparative, multicenter trial, patients chronically infected by HCV who were nonresponders to a previous treatment by PEG-IFN and ribavirin were restarted on a regimen of PEG-IFN-a-2a (180 mu g/week)?+?ribavirin (10001200?mg/day) for 16 weeks. If HCV-RNA decreased less than 2 log10 copies/mL (nonresponders), and if PEG-IFN-a-2a and ribavirin dosages were unchanged while tolerance was good, IFN?-1b (100 mu g three times per week) was added for the last 32 weeks of treatment. Virological response was evaluated at week 28 (12 weeks after initiation of IFN-?-1b). Results Among the 48 patients started on dual therapy, 23 patients (47%) were nonresponders at week 12 and received IFN-?-1b from week 16 onward. Their mean HCV-RNA (log10 IU/mL) was 6.83 at baseline, 5.81 at week 12, and 5.63 at week 28. No patient reached undetectable HCV-RNA at week 28 (upper bound of 95% confidence interval: 14.8%); none had a decrease >?1 log10 IU/mL. One case of grade 4 neutropenia was reported. Conclusion Among the strictly selected nonresponders, IFN-?-1b (at a dosage of 100 mu g thrice a week) in combination with PEG-IFN-a-2a and ribavirin failed to show virological efficacy.