Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.
To better understand the dynamics of hepatitis C virus and the antiviral effect of interferon-alpha-2b (IFN), viral decline in 23 patients during therapy was analyzed with a mathematical model. The analysis indicates that the major initial effect of IFN is to block virion production or release, with blocking efficacies of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units, respectively. The estimated virion half-life (t1/2) was, on average, 2.7 hours, with pretreatment production and clearance of 10(12) virions per day. The estimated infected cell death rate exhibited large interpatient variation (corresponding t1/2 = 1.7 to 70 days), was inversely correlated with baseline viral load, and was positively correlated with alanine aminotransferase levels. Fast death rates were predictive of virus being undetectable by polymerase chain reaction at 3 months. These findings show that infection with hepatitis C virus is highly dynamic and that early monitoring of viral load can help guide therapy.
Department of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
A U
AU
Neumann
N P
NP
Lam
H
H
Dahari
D R
DR
Gretch
T E
TE
Wiley
T J
TJ
Layden
A S
AS
Perelson
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007700:Kinetics; D008954:Models, Biological; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012044:Regression Analysis; D019562:Viral Load; D014766:Viremia / Q000821:virology; D014771:Virion / Q000502:physiology; D014779:Virus Replication
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase