van Bömmel Florian, Wünsche Thomas, Mauss Stefan, Reinke Petra, Bergk Alexandra, Schürmann Dirk, Wiedenmann Bertram, Berg Thomas
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité, Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany.
Hepatology. 2004 Dec;40(6):1421-5. doi: 10.1002/hep.20464.
Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant 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 log10 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 = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion, tenofovir may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection.
阿德福韦酯最近被批准用于治疗野生型和拉米夫定耐药的乙型肝炎病毒（HBV）感染。替诺福韦酯是阿德福韦的同类物，用于治疗HIV感染患者，最近已证明其对拉米夫定耐药的HBV感染患者也有效。因此，我们在一项针对53例患者的研究中比较了这两种药物，这些患者的定义为HBV DNA水平高（>6 log10拷贝/mL）且有拉米夫定耐药的基因证据。35例患者接受替诺福韦治疗72至130周，18例患者接受阿德福韦治疗60至80周。在48周的整个期间跟踪HBV DNA水平的变化。在每组5例患者的匹配亚组中比较早期病毒动力学。单独来看，所有接受替诺福韦治疗的患者，无论是否合并感染HIV或无合并症，在几周内均显示出对HBV DNA的强烈且早期抑制。相比之下，在阿德福韦组中观察到HBV DNA下降存在相当大的个体差异。因此，在第48周时，这些患者中只有44%的HBV DNA水平低于10⁵拷贝/mL，而替诺福韦治疗的患者为100%（P = 0.001）。两组均未发现严重副作用。长期（长达130周）来看，在接受替诺福韦治疗的患者中未发现表型病毒耐药的证据。总之，替诺福韦可能成为治疗拉米夫定耐药HBV感染患者的有效替代药物。
