Clearance kinetics of hepatitis C virus under different antiviral therapies

Interferon alpha (IFN) has been the standard treatment for hepatitis C virus (HCV) infection. Using the kinetic curves of viral clearance, this study compared three treatment regimes based on IFN alone or in combination with Amantadine or Ribavirin to determine the mechanisms of action and the most suitable way to use these drugs. The early clearance kinetics of HCV were studied in 22 patients with chronic hepatitis C under different antiviral treatments: IFN 3 MU daily (7 pts); IFN 3 MU daily plus Amantadine 200 mg (7 pts); and IFN 3 MU daily plus Ribavirin 1-1.2 gr (8 pts), for 6 months. HCV-RNA was assessed qualitatively and quantitatively on serial samples. The HCV-RNA decay curves suggested a different behaviour of viral clearance induced by the three treatments. While no significant differences were present in the first 6 hours, between 6 to 12 hours Ribavirin induced a rapid decline in the viral load. Amantadine seemed to accelerate it in the third phase (12 to 30 hours) and to provoke a more pronounced viral decline when compared to IFN alone (P < 0.05) or to IFN plus Ribavirin (P < 0.025) (baseline to 30 hours). Thus, while IFN remains the principal antiviral drug, Amantadine upholds the viral decline. Ribavirin, although synergistic with IFN, does not seem to improve the IFN effect during the earliest phase of treatment but probably supports the effects of IFN later on. A new dynamic approach to HCV treatment can therefore be developed.