Modeling population heterogeneity in viral dynamics for chronic hepatitis C infection: Insights from Phase 3 telaprevir clinical studies

摘要: Viral dynamic modelling has proven useful for designing clinical studies and predicting treatment outcomes patients infected with the hepatitis C virus. Generally these models aim to capture predict on-treatment viral load dynamics from a small study of individual patients. Here, we explored extending (1) numerous (2) by incorporating additional data types, including sequence prior response interferon. Data Phase 3 direct-acting antiviral telaprevir (T; total daily dose 2250 mg) combined pegylated-interferon alfa ribavirin (PR) were used analysis. The following in treatment-naive population reserved verify model: T/PR regimen where T was dosed every 8 h weeks (T8(q8h)/PR) twice 12 (T12(b.i.d.)/PR). resulting model accurately predicted sustained virologic rates both dosing regimens breakthrough characteristics T8(q8h)/PR regimen. Since observed variants depend on exposure, second verification suggested that correctly sensitive different even though developed using another Furthermore, b.i.d. comparable q8h PR-experienced population, comparison not been made controlled study. methods this work estimate variability occurring below limit detection critical making accurate predictions.