Although adefovir dipivoxil(ADV) has a unique profile of delayed and infrequent resistance in treatment-naive chronic hepatitis B patients,the association of ADV resistance with previous lamivudine(LAM) resistance is not well understood.We compared the emergence of the ADV-resis-tant mutations rtA181V/T and rtN236T between LAM-resistant patients and treatment-naive patients at 48 weeks of ADV monotherapy.Fifty-seven LAM-resistant patients and 38 treatment-n ve patients were treated with 10 mg/d ADV for more than 48 weeks.Both baseline and 48-week blood samples were analyzed for ADV-resistant mutations via restriction fragment mass polymorphism analysis.Antiviral responses were evaluated according to changes in serum HBV DNA(measured via real-time polymerase chain reaction) and alanine aminotransferase(ALT) levels and loss of hepatitis B e antigen(HBeAg) .After 48 weeks,10(18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations,whereas none of the 38 treatment-n ve patients developed such mutations(P <.01) .Among LAM-resistant patients,the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations(-1.04 vs.-2.63 log10 copies/mL) (P =.01) .However,the rates of serum ALT normalization(60% vs.55%) and HBeAg loss(14% vs.21%) were not significantly different between the 2 groups(P >.05) .In conclusion,the emergence of the rtA181V/T and rtN236T mutations was more common in LAM-resistant patients than in treatment-n ve patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment. Of adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment-naive chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV-resis -tant mutations rtA181V / T and rtN236T between LAM-resistant patients and treatment-naive patients for 48 weeks of ADV monotherapy. Ftyty-seven LAM-resistant patients and 38 treatment-n ve patients were treated with 10 mg / d ADV for more than 48 weeks.Both baseline and 48-week blood samples were analyzed for ADV-resistance mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (via via-polymerase polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations, none none of the 3 8 treatment-n ve patients developed such mutations (P <.01). Among LAM-resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations (-1.04 vs .-2.63 log10 copies / mL) (P = .01) .Wever, the rates of serum ALT normalization (60% vs.55%) and HBeAg loss (14% vs.21%) were not significantly different between the 2 groups (P> .05). In conclusion, the emergence of the rtA181V / T and rtN236T mutations was more common in LAM-resistant patients than in treatment-n ve patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment.