Telbivudine Plus Adefovir Versus Lamivudine Plus Adefovir for Lamivudine-Resistant Chronic Hepatitis B: TeSLA Randomized Trial

Abstract

Background: In countries with unavailable tenofovir, a combination of lamivudine (LMV) and adefovir (ADV) is recommended for the treatment of LMV-resistant chronic hepatitis B (CHB). Considering that telbivudine (L-dT) was demonstrated to be superior to LMV in previous studies, L-dT and ADV combination therapy is expected to show better antiviral efficacy than the combination of LMV and ADV in patients with LMV-resistant CHB. Methods: This was a prospective randomized multicenter study. The primary endpoint was Hepatitis B Virus (HBV) DNA reduction after 52 weeks of treatment. The secondary endpoints were HBV DNA undetectability, hepatitis B e antigen seroconversion, the incidence of virological and biochemical breakthroughs, and safety during the study period. Results: A total of 43 LMV-resistant CHB patients were enrolled. Twenty-one were treated with LMV + ADV and 22 with L-dT + ADV. After 52 weeks of antiviral treatment, the HBV DNA reduction showed no significant intergroup difference (-4.54 ± 1.23 log IU/mL in the LMV + ADV group, -4.24 ± 1.46 log IU/mL in the L-dT + ADV group, P = 0.475). There were no significant intergroup differences in HBV DNA undetectability rates, mean HBV DNA level, or hepatitis B e antigen seroconversion rate at 13, 26, 39, and 52 weeks of treatment. In terms of safety, the mean creatine phosphokinase level was significantly higher in the L-dT + ADV group. Conclusions: In the treatment of LMV-resistant CHB, the combination of L-dT and ADV did not show any clinical benefit compared to the combination of LMV and ADV.