University of Michigan, Ann Arbor, MI, USA.
BACKGROUND & AIMS:
Entecavir and tenofovir disoproxil fumarate (TDF) are potent antiviral agents that might have additive or synergistic antiviral activity in treatment of patients with chronic hepatitis B (CHB). We compared the efficacy and safety of entecavir monotherapy with those of a combination of entecavir and TDF.
We performed a randomized, open-label, multi-center, superiority study of 379 nucleos(t)ide-naïve patients with hepatitis B e antigen (HBeAg)+ (n=264) or HBeAg- (n=115) CHB. Subjects were given 0.5 mg entecavir (n=182) or a combination of 0.5 mg entecavir and 300 mg TDF 300 (n=197) for 100 weeks.
At Week 96, comparable proportions of patients each study arm achieved the primary endpoint of a level of hepatitis B virus (HBV) DNA <50 IU/mL (83.2% vs 76.4%; P =.088). Among HBeAg+ patients, a greater proportion given combination therapy achieved levels of HBV DNA <50 IU/mL than those given entecavir alone (80.4% vs 69.8%; P =.046). However, this difference was observed only in patients with baseline levels of HBV DNA ≥108 IU/mL (79% vs 62%), and not in those with baseline levels of HBV DNA <108 IU/mL (83% in both arms). Rates of HBeAg loss and HBeAg seroconversion were comparable between groups, whereas rate of alanine aminotransferase normalization was greater in entecavir monotherapy group. No HBV variants associated with entecavir or TDF resistance were detected. Safety profiles were consistent with previous reports with entecavir or TDF monotherapy.
The antiviral efficacy of ETV monotherapy is comparable to that of ETV plus TDF in a mixed population of nucleos(t)ide-naïve patients with CHB (70% HBeAg+). The combination therapy could provide an incremental benefit to HBeAg+ patients with baseline levels of HBV DNA ≥108 IU/mL.