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 wild‐type HBV (−3.1 log10 copies/mL vs−3.4 log10 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.