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AIM: To compare the antiviral efficacy of adefovir (ADV) in lamivudine (LMV)-resistant patients with LMV treatment in nucleoside-na(i)ve patients, using serum samples collected sequentially during the course of treatment progressing from LMV to ADV.METHODS: Forty-four patients with chronic hepatitis B (CHB) were included. The patients were initially treated with LMV and then switched to ADV when LMV resistance developed. Antiviral efficacy was assessed by measuring the following: reduction in serum HBV DNA from baseline, HBV DNA negative conversion (defined as HBV DNA being undectable by the hybridization assay),and HBV DNA response (either HBV DNA level ≤ 105 copies/mL or a ≥ 2 log10 reduction from baseline HBV DNA level).RESULTS: After two and six months of treatment, HBV DNA reduction was greater with LMV compared to ADV treatment (P = 0.021). HBV DNA negative conversion rates were 64% and 27% after one month of LMV and ADV treatment respectively (P = 0.001). Similarly, HBV DNA response rates were 74% and 51% after two months of LMV and ADV treatment respectively (P = 0.026).The time taken to HBV DNA negative conversion and to HBV DNA response were both delayed in ADV treatment compared with LMV.CONCLUSION: The antiviral efficacy of ADV in LMV-resistant patients is slower and less potent than that with LMV in nucleoside-na(i)ve patients during the early course of treatment.