Clearance kinetics of hepatitis C virus under different antiviral therapies

Abstract

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.

Evaluation of amantadine in chronic hepatitis C: a meta-analysis

“…Among 107 references identified, 76 studies were excluded for the following reasons: 23 studies were nonrandomized [16,; 12 studies did not mention ETR or SR [45][46][47][48][49][50][51][52][53][54][55][56]; 20 studies did not compare treatment with and without amantadine but other combinations of treatments including amantadine [18,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]; 2 studies concerned HIV-HCV co-infected patients [76,77]; 2 studies were performed in transplanted patients [78,79]; 1 study did not specify whether patients had received previous therapy or not [80]; 2 did not specify the exact number of patients randomized [81,82]; 14 preliminary studies were excluded as the latest publication of the trial was available [83][84][85][86][87]…”

Peginterferon α-2a Combination Therapies in Chronic Hepatitis C Patients Who Relapsed After or Had a Viral Breakthrough on Therapy with Standard Interferon α-2b Plus Ribavirin: A Pilot Study of Efficacy and Safety

“…AMD had been reported to be effective in treating patients with hepatitis C (23, 24) but confirmation of its effectiveness as monotherapy has proved elusive (25) and a plausible mechanism of action (26) remains to be established. The combination of interferon plus AMD was effective in one trial of 200 patients (14) and in a trial of elderly patients (27), but it was generally ineffective in most clinical trials (15)(16)(17)(18)(19)(20). The combination of interferon plus AMD was also generally ineffective in patients nonresponsive to interferon alone (28)(29)(30)(31) or interferon plus RBV (30).…”

“…AMD, which has been used primarily for the prophylaxis and treatment of respiratory tract infections caused by influenza A virus, is believed to prevent the entry of viruses into host cells (12). In patients with chronic HCV infection, the addition of AMD to interferon or interferon plus RBV treatment regimens has shown conflicting results (13)(14)(15)(16)(17)(18)(19)(20).…”

Twenty-four hour kinetics of hepatitis C virus and antiviral effect of alpha-interferon

“…Virol. DOI 10.1002/jmv given IFN-a alone, IFN-a plus ribavirin or pegylated IFN-a [Zeuzem et al, , 2001Torre et al, 2001]. These compounds all influence mainly the second phase of viral decline [Zeuzem et al, , 2001, whereas their impact on the first phase is weak.…”