Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy

Avidan U. Neumann, Nancy P. Lam, Harel Dahari, David R. Gretch, Thelma E. Wiley, Thomas J. Layden, Alan S. Perelson

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    1941 Scopus citations

    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 vital 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.

    Original languageEnglish
    Pages (from-to)103-107
    Number of pages5
    JournalScience
    Volume282
    Issue number5386
    DOIs
    StatePublished - 2 Oct 1998

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