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


METHODS
In this paper, we developed the decreasing effectiveness (DE) model, a new mathematical model that allows the drug effectiveness to change with time.


RESULTS
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.


CONCLUSIONS
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.
Shudo
Emi
E
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Ribeiro
Ruy M
RM
Talal
Andrew H
AH
Perelson
Alan S
AS
D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D008954:Models, Biological; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b