Emergence of adefovir-resistant mutants after reversion to YMDD wild-type in lamivudine-resistant patients receiving adefovir monotherapy

Background: To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine ( LAM)resistant patients. Methods: We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method. Results: Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wildtype HBV (-3.1 log(10) copies/mL vs -3.4 log(10) copies/mL, P > 0.05). Conclusions: ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.