Abstract

Biphasic modeling of viral kinetics provided valuable information to rapidly assess potential antiviral regimens during the beginning of therapy, but has not been performed over the long term. In 11 chronic hepatitis B patients with lamivudine treated per day, the model with delay time was applied to examine phase transition and analyze viral kinetics parameters. Viral decay conformed to a biphasic mode during the first 4 weeks, with the complex profile appeared in the later period. Lamivudine treatment resulted in a mean log hepatitis B virus (HBV)-DNA decline of 1.77 +/- 0.55 after 4 weeks and 3.79 +/- 1.70 log after 24 weeks. The median effectiveness of blocking viral replication was 96% (range, 89-99%). The median rate of free virus clearance and infected cell loss was 1.1/day and 0.03/day, respectively. Through phase transition determination and stepwise modeling process, viral kinetics were evaluated for complex decay profile during long-term therapy. Moreover, with the abnormal kinetics tracked, an occasion of add-on combined therapy was developed to treat patients with emerging virus mutants. The present study using mathematical modeling of viral decay may be a useful approach to evaluate optimal individualized therapy for HBV infection in a continuous long-term manner.

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