A Multi-Variant, Viral Dynamic Model of Genotype 1 HCV to Assess the in vivo Evolution of Protease-Inhibitor Resistant Variants
Figure 7
Comparison of cases with (δdrug≠0) and without (δdrug = 0) telaprevir-enhanced infected-cell clearance rate constants.
In δdrug≠0, δdrug was estimated from data while δnodrug was fixed at the average value for Peg-IFN/RBV treatment (5.2×10−3 h−1); in δdrug = 0 case, δnodrug was estimated from data while δdrug was fixed at zero. Panel a, objective values for both cases. The values with δdrug = 0 were higher than those with nonzero δdrug, suggesting better correspondence of data and model fit with δdrug≠0. The number of parameters estimated in both cases is the same. Panels b and c, correspondence between plasma HCV RNA (b) and variant prevalence (c) data and best-fit models for Subject 1. Legends: solid lines, best-fit models with δdrug = 0 case; dotted lines, best-fit models with δdrug≠0 case; dashed lines, variant HCV RNA predicted by best-fit models with δdrug = 0 case. Without δdrug, the best-fit model must trade-off the fitting error on during-dosing second phase decline to match prolonged variants persistence at post-dosing.