Mathematical modeling of viral kinetics: a tool to understand and optimize therapy.
One theme that continues to emerge from these studies is the relevance and need for a strong IFN effectiveness. In the prediction studies, the importance of IFN effectiveness for eventual clearance of the virus is present. In the study by Layden et al, the relevance of the viral load at the end of the first phase and IFN effectiveness, to the subsequent second-phase viral decline, is discussed. In the recently developed triphasic model by Bergmann et al, it is illustrated how, theoretically, the viral load at the end of the first phase could impact the second-phase viral decline and eventual clearance of the virus. And, in the investigation into the difference in viral dynamics between African Americans and Caucasians, it appears that a strong effectiveness and first-phase log drop is crucial for virus eradication. More work needs to be completed to understand better why the effectiveness is so crucial for elimination of the virus, and why the effectiveness varies so significantly from one person to another, or from one genotype to another. In a rather short time, the study of viral kinetics has improved our understanding of HCV infection, especially in relation to treatment response. Information has been gleaned on the rapid turnover and clearance rate of the virus, the mode of action of IFN, and the dose-dependence of IFN in inhibiting viral production. Such information has been used to challenge the way we treat patients, understand the difference between nonresponders and responders, gain insight into possible mechanisms of treatment resistance, and predict treatment response. As newer drugs emerge, viral kinetic studies should be able to shed light on the dose-dependent efficacy and mode of action of these newer forms of therapy. The use of kinetics needs to be extended to other areas, such as the study and treatment of acute HCV infection as well as following liver transplantation (see article by Drs. Pawlotsky and Rosen). If the past is any indication of the usefulness of mathematical modeling and kinetics in the study of viruses, continued employment of these tools will only prove beneficial.
Layden
Thomas J
TJ
Department of Medicine, College of Medicine, University of Illinois at Chicago, 840 South Wood/Mail Code 787, Chicago, IL 60612, USA. tjlayden@uic.edu
Layden
Jennifer E
JE
Ribeiro
Ruy M
RM
Perelson
Alan S
AS
D000998:Antiviral Agents / Q000627:therapeutic use; D006678:HIV / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology*; D006515:Hepatitis B virus / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007700:Kinetics; D008954:Models, Biological; D014779:Virus Replication
D000998:Antiviral Agents; D016898:Interferon-alpha