The kinetics of hepatitis C virus infection.
Mathematical modeling of viral dynamics reveals high turnover rates of pretreatment viral production and clearance (10(11)-10(13) virions/day) and permits the estimation of in-vivo half-lives of a few hours for HCV free virions. The balance between virus production and clearance in untreated patients with chronic hepatitis C virus results in a decline of viremia when active antiviral treatment is initiated. During the first phase of IFN-alpha therapy, the kinetics of the viral load is characterized by a rapid, dose-dependent decline. After about 24 to 48 hours, the viral decline enters a second phase of a relatively slow exponential decay during the following weeks of therapy which may reflect the death rate of infected hepatocytes. The second-phase decay is predictive for the virologic end-of-treatment status and, even more so, for the likelihood of sustained response. Nonresponding patients typically show constant viremia or even a rebound during this second phase.
Zeuzem
S
S
Department of Medicine, Division of Gastroenterology and Hepatology, University of Frankfurt a.M., Germany. zeuzem@em.uni-frankfurt.de
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007700:Kinetics; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a