Mathematical modeling based on lamivudine switching to adefovir dipivoxil and to entecavir anti-hepatitis B infection treatment

Lamivudine (LVD) is one of the popular drugs to be used for anti-hepatitis B virus infection therapy. About 39% HBeAg-positive chronic hepatitis B (CHB) patients can achieve serum hepatitis B virus (HBV) DNAs below the low limit of test after one years´ treatment. However the antiviral-resistance HBV mutation to LVD treatment is near 60% after three year´s therapy. Combination treatment is one method to such kind patients. Based on a LVD mutation (YMDD mutation) CHB patient´s clinic data and our improved basic virus infection model, this paper introduces a mathematical model whose parameters change according to different therapy periods. Numerical simulations show that the simulated HBV DNA levels are in good agreement with the HBV DNA evolution of the patient´s therapy for switching lamivudine (LVD) + placebo to adefovir dipivoxil (AD) and then to entecavir (EV). The model predicts that it needs about 9 years to clean the patient´s all infected liver cells if the patient´s immune functions can be kept after the therapy.