Viral Kinetics in Genotype 1 Chronic Hepatitis C Patients During Therapy With 2 Different Doses of Peginterferon alfa-2b Plus Ribavirin

Hepatology. 2002 Apr;35(4):930-6. doi: 10.1053/jhep.2002.32150.

Abstract

Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 microg/kg for 1 week, 1.5 microg/kg for 3 weeks, and 1.0 microg/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 microg/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 +/- 0.86 log vs. 5.15 +/- 1.04 log). The 3-microg/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-microg/kg dose during the first 48 hours (2.08 +/- 0.93 log vs. 1.09 +/- 0.80 log; P <.001) and both increased at 72 hours (0.54 +/- 0.73 log vs. 0.03 +/- 0.36 log; P = not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 +/- 0.99 log vs. 0.72 +/- 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha* / administration & dosage*
  • Interferon-alpha* / adverse effects
  • Interferon-alpha* / therapeutic use
  • Kinetics
  • Male
  • Middle Aged
  • Polyethylene Glycols*
  • RNA, Viral / analysis
  • Recombinant Proteins
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Time Factors

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • peginterferon alfa-2a