A hepatitis C viral kinetic model that allows for time-varying drug effectiveness

The standard model of hepatitis C virus (HCV) dynamics under high-dose daily interferon (IFN) therapy assumed that the drug effectiveness remains constant. However, for treatment with pegylated (PEG)-IFN-alpha2b dosed weekly, drug levels fall substantially and viral load rebounds have been observed...

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Bibliographic Details
Published in:Antiviral therapy 2008-01, Vol.13 (7), p.919-926
Main Authors: SHUDO, Emi, RIBEIRO, Ruy M, TALAL, Andrew H, PERELSON, Alan S
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Antiviral Agents - administration & dosage
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Biological and medical sciences
Drug Therapy, Combination
Hepacivirus - drug effects
Hepacivirus - physiology
Hepatitis C virus
Human viral diseases
Humans
Infectious diseases
Interferon-alpha - administration & dosage
Interferon-alpha - pharmacology
Interferon-alpha - therapeutic use
Kinetics
Medical sciences
Models, Biological
Pharmacology. Drug treatments
Polyethylene Glycols
Recombinant Proteins
Ribavirin - administration & dosage
Ribavirin - pharmacology
Ribavirin - therapeutic use
RNA, Viral - blood
RNA, Viral - drug effects
Time Factors
Treatment Outcome
Viral diseases
Viral hepatitis
Viral Load
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Summary:The standard model of hepatitis C virus (HCV) dynamics under high-dose daily interferon (IFN) therapy assumed that the drug effectiveness remains constant. However, for treatment with pegylated (PEG)-IFN-alpha2b dosed weekly, drug levels fall substantially and viral load rebounds have been observed toward the end of the weekly dosing interval, implying non-constant drug efficacy. In this paper, we developed the decreasing effectiveness (DE) model, a new mathematical model that allows the drug effectiveness to change with time. The DE model can describe viral load rebounds as well as other viral kinetic patterns observed in clinical practice, such as biphasic viral declines. We applied the DE model to the HCV RNA kinetic data under PEG-IFN-alpha2b therapy. The average drug effectiveness during the first week of therapy estimated in the DE model agreed with the one estimated from HCV RNA kinetic data plus pharmacokinetic data. We illustrated the usefulness of the DE model by analysing HCV RNA data from patients who received PEG-IFN-alpha2b once weekly plus daily ribavirin.
ISSN:1359-6535
2040-2058
DOI:10.1177/135965350801300711