Viral kinetics and mathematical models.

Abstract

Mathematical models can provide insights into the dynamics of viral diseases. Methods that were introduced to analyze human immunodeficiency virus dynamics in vivo can be modified to give insights into hepatitis C virus (HCV) dynamics, the mechanisms of action of interferon, and the consequences of giving different dosages of interferon. Patients received doses of 5, 10, or 15 mIU of interferon daily for 14 days followed by maintenance therapy of 5 mIU daily until day 90. HCV-RNA levels in serum dropped rapidly over the first 1 to 2 days of therapy. Comparing the kinetics of this response with mathematical models suggests that interferon acts by blocking the production or release of HCV virions from infected cells. The analysis further indicates that a daily dose of 5 mIU blocks approximately 80% of HCV production, and doses of 10 and 15 mIU block approximately 95% of HCV production. The serum level of HCV is approximately constant before treatment is initiated. Our model suggests that in order to maintain this constant level, on average, approximately 1 trillion virions are produced and cleared daily in an untreated HCV-infected person. The acute, rapid clearance of HCV, which occurs over the first 2 days of therapy, is followed by a slower phase of serum HCV decline. The rate of the second-phase decline may reflect the rate at which HCV-producing cells are killed, possibly by immune responses. Additional studies are needed to evaluate more fully the kinetics of the second-phase decline as well as its dose dependence and its predictive power with regard to eradication of HCV.