Abstract
Background
Here, we investigated the treatment response and evolution of HBV resistance during lamivudine (LAM) plus adefovir (ADV) and entecavir (ETV) monotherapy in patients with ADV-resistant mutants.
Methods
Of the 53 patients with ADV-resistant mutants, 25 received combined LAM plus ADV therapy (LAM+ADV group) and 28 received ETV monotherapy (ETV group) for at least 12 months (median 24 months and range 12–67 months).
Results
During 24 months therapy, no significant difference was noted in HBV DNA reduction from baseline, HBV DNA<200 copies/ml, hepatitis B e antigen loss and ALT normalization between the two groups. In the LAM+ADV group, patients with single rtN236T resistant mutation had higher rates of undetectable HBV DNA than those with the double mutant rtA181T/V+rtN236T at months 3–18 of therapy. No virological breakthrough occurred except for one patient with rtN236T resistant mutation who experienced virological and biochemical breakthrough after the emergence of an additional rtA181T mutant under LAM+ADV therapy. Of the 28 patients receiving ETV monotherapy, ETV-resistant mutants developed in 8. The cumulative rates of ETV-resistant mutations and virological breakthrough at months 12, 24 and 36 were 3.6%, 25.7% and 46.8%, respectively. ADV-resistant mutations were rapidly replaced by LAM-resistant mutations (median 12 months) followed by ETV-resistant mutations.
Conclusions
There was no significant difference in virological response between the LAM+ADV and ETV groups in patients with ADV-resistant mutants. LAM+ADV were less effective in patients with the double mutant rtA181T/V+rtN236T than the single rtN236T mutation. The incidence of ETV-resistant mutation was high in patients with LAM/ADV-resistant mutants treated with ETV monotherapy.