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: epsilon, of blocking viral production, the clearance: c, of free virus, and the loss of infected cells: delta. RESULTS: Median epsilon was 98%, median c was 0.7/day, and median delta 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, epsilon was lower (P=0.026) and delta 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.
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: epsilon, of blocking viral production, the clearance: c, of free virus, and the loss of infected cells: delta. RESULTS: Median epsilon was 98%, median c was 0.7/day, and median delta 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, epsilon was lower (P=0.026) and delta 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.
Authors: Nancy W Y Leung; Eva Herrmann; George K K Lau; Henry L Y Chan; Tokutei M K So; Stefan Zeuzem; Yu Dong; Aldo Trylesinski; Nikolai V Naoumov Journal: Infect Dis Ther Date: 2014-09-17