Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection.

ABSTRACT: Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance a

SUBMITTER: Ke R 

PROVIDER: S-EPMC4488346 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature