Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
Gut. 2016 Jun;65(6):1042-51. doi: 10.1136/gutjnl-2014-308435. Epub 2015 Mar 23.
Little clinical data are available regarding the optimal treatment of patients who harbour adefovir-resistant HBV.
In this multicentre trial, patients who had adefovir-resistant HBV with serum HBV DNA levels >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=50) or TDF and entecavir (ETV, 1 mg/day) combination therapy (TDF/ETV, n=52) for 48 weeks. All who completed 48 weeks in either group received TDF monotherapy for 48 additional weeks.
Baseline characteristics were comparable between groups, including HBV DNA levels (median, 3.38 log10 IU/mL). All patients had adefovir-resistant HBV mutations; rtA181V/T and/or rtN236T. The proportion of patients with HBV DNA <15 IU/mL was not significantly different between the TDF-TDF and TDF/ETV-TDF groups at weeks 48 (62% vs 63.5%; p=0.88) and 96 (64% vs 63.5%; p=0.96). The mean change in HBV DNA levels from baseline was not significantly different between groups at week 48 (-3.03 log10 IU/mL vs -3.31 log10 IU/mL; p=0.38). Virological breakthrough occurred in one patient on TDF-TDF and two patients on TDF/ETV-TDF over 96 weeks; all were attributed to poor drug adherence. At week 96, five and two patients in the TDF-TDF and TDF/ETV-TDF groups, respectively, retained some of their baseline resistance mutations (p=0.44). None developed additional resistance mutations. Safety profiles were comparable in the two groups.
In patients with adefovir-resistant HBV and multiple-drug failure, TDF monotherapy provided a virological response comparable to that of TDF and ETV combination therapy, and was safe up to 96 weeks.
NCT01639066.
关于阿德福韦耐药 HBV 患者的最佳治疗方法，临床数据较少。
在这项多中心试验中，血清 HBV DNA 水平>60IU/mL 的阿德福韦耐药 HBV 患者被随机分为接受富马酸替诺福韦二吡呋酯（TDF，300mg/天）单药治疗（n=50）或 TDF 和恩替卡韦（ETV，1mg/天）联合治疗（TDF/ETV，n=52）48 周。所有完成任何一组 48 周治疗的患者均加用 TDF 单药治疗 48 周。
两组的基线特征相当，包括 HBV DNA 水平（中位数，3.38log10IU/mL）。所有患者均存在阿德福韦耐药 HBV 突变；rtA181V/T 和/或 rtN236T。48 周（62%比 63.5%；p=0.88）和 96 周（64%比 63.5%；p=0.96）时，TDF-TDF 组和 TDF/ETV-TDF 组 HBV DNA<15IU/mL 的患者比例无显著差异。48 周时，两组患者 HBV DNA 水平自基线的平均变化无显著差异（-3.03log10IU/mL 比-3.31log10IU/mL；p=0.38）。96 周时，TDF-TDF 组和 TDF/ETV-TDF 组各有 1 例和 2 例患者发生病毒学突破，均归因于药物依从性差。96 周时，TDF-TDF 组和 TDF/ETV-TDF 组分别有 5 例和 2 例患者保留了部分基线耐药突变（p=0.44）。两组均未出现新的耐药突变。两组的安全性特征相当。
在阿德福韦耐药 HBV 且多重耐药失败的患者中，TDF 单药治疗提供的病毒学应答与 TDF 和 ETV 联合治疗相当，安全性可至 96 周。
NCT01639066。
