MODELING EVOLUTIONARY DYNAMICS OF HEPATITIS-C RESISTANT VARIANTS IN PATIENTS DOSED WITH TELAPREVIR

摘要

The invention relates to a method of measuring and predicting the evolutionary dynamics of HCV genotype 1 population when dosed with a composition including a protease inhibitor. The method includes using a multivariant viral kinetic model consisting of two-step process of random mutation and selection by competition among various HCV variants for shared limited healthy target cells constituting replication space to measure and predict the evolutionary dynamics of HCV genotype (1) population thereby providing useful information on dosing and responsiveness to compositions including a protease inhibitor. The model parameters are estimated from pre-, during-, and post-dosing plasma HCV RNA and post-dosing clonal sequencing data using a scheme that integrates all dosing periods to impose consistency and to improve estimation results.