Multi-scale model for hepatitis C viral load kinetics under treatment with direct acting antivirals

Virus Res. 2016 Jun 15:218:96-101. doi: 10.1016/j.virusres.2015.09.011. Epub 2015 Sep 25.


Hepatitis C virus (HCV) infections are a global health problem, and extensive research over the last decades has been targeted at understanding its molecular biology and developing effective antiviral treatments. Recently, a number of potent direct acting antiviral drugs have been developed targeting specific processes in the viral life cycle. Here, we developed a mathematical multi-scale model of the within-host dynamics of HCV infection by integrating a standard model for viral infection with a detailed model of the viral replication cycle inside infected cells. We use this model to study patient time courses of viral load under treatment with daclatasvir, an inhibitor of the viral non-structural protein NS5A. Model analysis predicts that treatment efficacy can be increased by combining daclatasvir with dedicated viral polymerase inhibitors, corresponding to promising current strategies in drug development. Hence, our model presents a predictive tool for in silico simulations, which can be used to study and optimize direct acting antiviral drug treatment.

Keywords: Direct acting antiviral treatment; Hepatitis C virus; Ordinary differential equations model; Pharmacodynamics; Viral kinetics.

MeSH terms

  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / pharmacology
  • Carbamates
  • Drug Synergism
  • Drug Therapy, Combination
  • Gene Expression Regulation, Viral*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / growth & development
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Hepatocytes / drug effects
  • Hepatocytes / virology
  • Humans
  • Imidazoles / pharmacokinetics*
  • Imidazoles / pharmacology
  • Liver / drug effects
  • Liver / virology
  • Models, Statistical*
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / pharmacology
  • Pyrrolidines
  • RNA, Viral / antagonists & inhibitors
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Valine / analogs & derivatives
  • Viral Load / drug effects
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Protease Inhibitors
  • Pyrrolidines
  • RNA, Viral
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir