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 antivir al effect of interferon-alpha-2b (IFN), viral decline in 23 patients d uring therapy was analyzed with a mathematical model. The analysis ind icates that the major initial effect of IFN is to block virion product ion 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 p retreatment production and clearance of 10(12) virions per day. The es timated infected cell death rate exhibited large interpatient variatio n (corresponding t(1/2) = 1.7 to 70 days), was inversely correlated wi th baseline viral load, and was positively correlated with alanine ami notransferase 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.