Mathematical modeling of HCV infection and treatment.
In the last decade, viral kinetic modeling has played an important role in the analysis of HCV RNA decay after the initiation of antiviral therapy. Models have provided a means of evaluating the antiviral effectiveness of therapy and of estimating parameters, such as the rate of virion clearance and the rate of loss of HCV-infected cells, and they have suggested mechanisms of action for both interferon-alpha and ribavirin. The inclusion of homeostatic proliferation of infected and uninfected hepatocytes in existing viral kinetic models has allowed prediction of most observed HCV RNA profiles under treatment, for example, biphasic and triphasic viral decay and viral rebound to baseline values after the cessation of therapy. In addition, new kinetic models have taken into consideration the different pharmacokinetics of standard and pegylated forms of interferon and have incorporated alanine aminotransferase kinetics and aspects of immune responses to provide a more comprehensive picture of the biology underlying changes in HCV RNA during therapy. Here, we describe our current understanding of the kinetics of HCV infection and treatment.
Dahari
Harel
H
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Shudo
Emi
E
Ribeiro
Ruy M
RM
Perelson
Alan S
AS
D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007372:Interferons / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D008954:Models, Biological; D012367:RNA, Viral / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons