Viral dynamics in chronic hepatitis B patients during lamivudine therapy

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Abstract
Rationale and aim: Recently, we described a first-order decay model for the description of a decrease in viral load during treatment with lamivudine for a chronic hepatitis B virus infection (HBV). However, more frequent sampling of viral load during the first month of treatment shows a bi-phasic viral decline. We therefore compared several mathematical models which are currently in use to describe the dynamics of various viruses and treatments. Methods: HBV DNA positive chronic hepatitis B patients were treated with lamivudine 150–600 mg daily for four weeks. During the first two days, blood samples were drawn every 6 h, then daily during the first week and weekly during the following three weeks. HBV DNA was measured with the Digene Hybrid Capture II HBV DNA test and the sensitive Roche PCR assay, both calibrated on the Eurohep standard. Results: Our HBV DNA data are most accurately described if we use the bi-phasic model previously described by Neumann et al. while introducing all consecutive data of all patients simultaneously (mixed effects model). This results in an effectiveness of blocking of viral replication of 93%, a half-life of free virus of 17 h and a half-life of infected hepatocytes of 7 day in patients treated with 150 mg of lamivudine. Conclusion: HBV dynamics during treatment with lamivudine can be explained by blocking of virion production with or without blocking of de novo infection. The bi-phasic model as described by Neumann et al. in combination with frequent blood sampling provides the most accurate fit and can be used to compare new nucleoside analogue profiles to lamivudine therapy.