A perspective on modelling hepatitis C virus infection.
By mathematically describing early hepatitis C virus (HCV) RNA decay after initiation of interferon (IFN)-based antiviral therapy, crucial parameters of the in vivo viral kinetics have been estimated, such as the rate of production and clearance of free virus, and the rate of loss of infected cells. Furthermore, by suggesting mechanisms of action for IFN and ribavirin mathematical modelling has provided a means for evaluating and optimizing treatment strategies. Here, we review recent modelling developments for understanding complex viral kinetics patterns, such as triphasic HCV RNA declines and viral rebounds observed in patients treated with pegylated interferon and ribavirin. Moreover, we discuss new modelling approaches developed to interpret the viral kinetics observed in clinical trials with direct-acting antiviral agents, which induce a rapid decline of wild-type virus but also engender a higher risk for emergence of drug-resistant variants. Lastly, as in vitro systems have allowed a better characterization of the virus lifecycle, we discuss new modelling approaches that combine the intracellular and the extracellular viral dynamics.
Guedj
J
J
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Rong
L
L
Dahari
H
H
Perelson
A S
AS
D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a