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Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.

To better understand the dynamics of hepatitis C virus and the antiviral effect of interferon-alpha-2b (IFN), viral decline in 23 patients during therapy was analyzed with a mathematical model. The analysis indicates that the major initial effect of IFN is to block virion production or release, with blocking efficacies of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units, respectively. The estimated virion half-life (t1/2) was, on average, 2.7 hours, with pretreatment production and clearance of 10(12) virions per day. The estimated infected cell death rate exhibited large interpatient variation (corresponding t1/2 = 1.7 to 70 days), was inversely correlated with baseline viral load, and was positively correlated with alanine aminotransferase levels. Fast death rates were predictive of virus being undetectable by polymerase chain reaction at 3 months. These findings show that infection with hepatitis C virus is highly dynamic and that early monitoring of viral load can help guide therapy.

Pubmed ID: 9756471


  • Neumann AU
  • Lam NP
  • Dahari H
  • Gretch DR
  • Wiley TE
  • Layden TJ
  • Perelson AS


Science (New York, N.Y.)

Publication Data

October 2, 1998

Associated Grants

  • Agency: NIDDK NIH HHS, Id: A1/DK41320-2
  • Agency: PHS HHS, Id: A139049-2
  • Agency: NCRR NIH HHS, Id: RR06555

Mesh Terms

  • Alanine Transaminase
  • Antiviral Agents
  • Cell Death
  • Dose-Response Relationship, Drug
  • Half-Life
  • Hepacivirus
  • Hepatitis C
  • Humans
  • Interferon-alpha
  • Kinetics
  • Models, Biological
  • RNA, Viral
  • Recombinant Proteins
  • Regression Analysis
  • Viral Load
  • Viremia
  • Virion
  • Virus Replication