Hepatitis C virus kinetics

The balance of virus production and clearance for untreated patients with c hronic hepatitis C virus (HCV) results in a decline of viraemia when initia ting active antiviral treatment. During the first phase of interferon-alpha therapy, after a delay of about 8-9 h, the kinetics of the viral load is c haracterized by a rapid dose-dependent decline. This early response can be observed for almost all patients treated with interferon-alpha. After about 24-48 h, the viral decline enters a second phase of relatively slow expone ntial decay during the following weeks of therapy. Non-responding patients, however, show constant viraemia or even a rebound during this second phase . The rate of the exponential decline of the viral load in responding patie nts in this second phase is less sensitive to the dose of interferon-alpha and varies considerably among patients. Furthermore, combination therapy wi th interferon-alpha plus ribavirin does not significantly improve the initi al viral decay, although it may prevent more patients from rebounding. Math ematical modelling of viral dynamics reveals high turnover rates of pre-tre atment viral production and clearance, and permits the estimation of in viv o half-lives of a few hours for free HCV virions and of 1-70 days for produ ctively infected cells. Infected cell death rate, which determines the seco nd phase decline slope, is predictive of response to treatment. Current mod els indicate that the early biphasic viral decline is explained if interfer on-a partially blocks virion production from infected cells, yet they do no t rule out additional antiviral or immunological effects. Therapeutic impli cations are the advisability of use of frequent (daily) and comparatively h igh initial doses. In conclusion, kinetic analysis of the viral decay durin g the first weeks of treatment permits the prediction of response at the en d-of-therapy and might help to evaluate new drugs and to optimize therapy.