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Hepatitis C Viral Dynamics in Vivo and the Antiviral Efficacy of Interferon-α Therapy

Science  02 Oct 1998:
Vol. 282, Issue 5386, pp. 103-107
DOI: 10.1126/science.282.5386.103

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Abstract

To better understand the dynamics of hepatitis C virus and the antiviral effect of interferon-α-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 (t 1/2) was, on average, 2.7 hours, with pretreatment production and clearance of 1012 virions per day. The estimated infected cell death rate exhibited large interpatient variation (corresponding t 1/2 = 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.

  • * These authors contributed equally to this work.

  • To whom correspondence and questions regarding mathematical modeling and analysis should be addressed. E-mail: neumann{at}macs.biu.ac.il

  • To whom correspondence should be addressed. E-mail: NancyLam{at}uic.edu

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