John C Martin Foundation.

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Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudineresistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (>6 log 10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 10 5 copies/mL in contrast to 100% of the tenofovir-treated patients (P ‫؍‬ . T reatment of chronic hepatitis B virus (HBV) infection with the nucleoside analogue and reverse transcriptase inhibitor lamivudine has been shown to be very effective in suppressing HBV replication without major side effects. 1 In view of the long half-life of covalently closed circular HBV DNA and the variable turnover of infected hepatocytes, long-term treatment is required to achieve complete HBV elimination (i.e., hepatitis B surface antigen [HBsAg] loss). Unfortunately, the effect of this kind of treatment is often abolished by the selection of lamivudine-resistant mutants 2 followed by the reappearance of HBV DNA to baseline levels and reactivation of chronic hepatitis B.The efficacy of the acyclic nucleotide analogue adefovir dipivoxil (adefovir) in the treatment of wild-type and lamivudine-resistant HBV infection has been described, and a daily adefovir dose of 10 mg was recently approved for the treatment of chronic HBV infection. [3][4][5][6] Tenofovir disoproxil fumarate, another acyclic nucleotide analogue that is the pro-drug of tenofovir, has been approved as a novel oral agent for the treatment of human immunodeficiency virus (HIV) infection. Its effect in lamivudine drug resistance has been recently described by us as well as by other authors. [7][8][9][10][11][12][13][14] In view of the close structural relationship between these two drugs, we conducted a study in patients suffering from lamivudine drug resistance to compare their ef-