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

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.