Viral kinetics in patients with lamivudine-resistant hepatitis B during adefovir–lamivudine combination therapy,

Background/Aims Mathematical analysis of viral kinetics during lamivudine-adefovir combination therapy has not yet been performed in patients with lamivudine-resistant hepatitis B. Methods In 8 patients with lamivudine-resistant hepatitis B, adefovir dipivoxil (10 mg/day) was added to ongoing lamivudine. Viral decay during the first 8 weeks of combination therapy was described by a biphasic model to determine the efficacy: ε, of blocking viral production, the clearance: c, of free virus, and the loss of infected cells: δ. Results Median ε was 98%, median c was 0.7/day, and median δ was 0.07/day. No significant association was found between viral kinetic and baseline parameters and virologic and biochemical treatment response. When compared with viral kinetic constants reported for higher dose adefovir dipivoxil monotherapy, ε was lower (P=0.026) and δ was higher (P=0.008) in this study whereas c did not differ between both studies. Conclusions Although a recent study did not show any differences in the reduction of HBV DNA comparing monotherapy with adefovir dipivoxil to adefovir–lamivudine combination therapy in patients with lamivudine-resistant chronic hepatitis B, mathematical analysis of early viral kinetics suggests an additional effect of lamivudine on the infected cell loss during adefovir–lamivudine combination therapy