Open AccessMultiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
Author(s) -
Woot de Trixhe Xavier,
Krzyzanski Wojciech,
Vermeulen An,
PerezRuixo Juan José
Publication year - 2021
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12604
Subject(s) - telaprevir , intracellular , hepatitis c virus , ribavirin , pegylated interferon , population , virology , virus , viral load , interferon , immunology , medicine , biology , biochemistry , environmental health
This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the direct‐acting antiviral effect on intracellular processes, which can then be integrated with the viral kinetics within the host while accounting for the interindividual variability between patients. This should allow an exploration of the treatment effect within the entire chronic HCV‐infected population.