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-α2b 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-α2b 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-α2b once weekly plus daily ribavirin.