Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B
Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B
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DOI：
10.1136/gut.2010.223206
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发表时间：
2011-02-01
期刊：
影响因子：
24.5
通讯作者：
Angus, P. W.
中科院分区：
文献类型：
--
作者：
Patterson, S. J.;George, J.;Angus, P. W.
目的观察富马酸替诺福韦酯（TDF）治疗拉米夫定（LAM）治疗失败且有明显病毒复制的慢性B型肝炎病毒（HBV）感染的疗效（如果HBeAg阳性，HBV DNA > 10（5）拷贝/ml，> 10（4）拷贝/ml，如果HBeAg阴性），尽管使用阿德福韦酯（ADV）治疗至少24周。TDF每日300 mg标签研究。基线前接受联合阿德福韦酯/LAM的患者转为TDF/LAM.Setting多个三级转诊中心。中位年龄为48.5岁（范围21-80岁），46例（77%）为男性，40例（67%）为HBeAg阳性。38例患者（63%）从ADV转换为TDF，其余患者从ADV/LAM转换为TDF/LAM。在基线时，分别有20例患者（33%）和17例患者（28%）存在对LAM或ADV耐药的替代。中位基线病毒载量为5.33 log（10）IU/ml（范围2.81-8.04）。最初接受TDF单药治疗且在24周或24周后持续病毒复制的患者转换为TDF/LAM。主要结果指标为HBV病毒载量较基线的变化和达到不可检测病毒载量（< 15 IU/ml）的患者百分比。1例患者在第10天因皮疹停用TDF。从基线至第12周病毒载量的时间加权变化总体为-2.19 log（10）IU/ml。从基线到第12、24、48和96周，HBV DNA的中位变化分别为-2.86、-3.23、-3.75和-4.03 log（10）IU/ml。在48周和96周时，27/59（46%）和38/59（64%）患者达到HBV DNA < 15 IU/ml。的反应是独立的基线LAM治疗或突变赋予ADV resistance.Conclusions在大量预处理的患者基因型耐药率高，TDF保留了显着的活性对HBV虽然这似乎减少了与幼稚患者的研究。
Objective To determine the efficacy of tenofovir disoproxil fumarate (TDF) in adults with chronic hepatitis B virus (HBV) infection who had previously failed lamivudine (LAM) and had significant viral replication (HBV DNA > 10(5) copies/ml if HBeAg positive, > 10(4) copies/ml if HBeAg negative) despite at least 24 weeks of treatment with adefovir dipivoxil (ADV).Design A prospective open-label study of TDF 300 mg daily. Patients receiving combination ADV/LAM prior to baseline were switched to TDF/LAM.Setting Multiple tertiary referral centres.Methods Sixty patients were enrolled. The median age was 48.5 years (range 21-80), 46 (77%) were male and 40 (67%) were HBeAg positive. Thirty-eight patients (63%) were switched from ADV to TDF, the remainder from ADV/LAM to TDF/LAM. At baseline, substitutions conferring resistance to LAM or ADV were present in 20 patients (33%) and 17 patients (28%), respectively. The median baseline viral load was 5.33 log(10) IU/ml (range 2.81-8.04). Patients initially treated with TDF monotherapy with persistent viral replication at or after 24 weeks were switched to TDF/LAM. The main outcome measures were change in HBV viral load from baseline and percentage of patients achieving an undetectable viral load (< 15 IU/ml).Results Results are reported at 96 weeks of treatment. One patient discontinued TDF at 10 days due to rash. The time-weighted change in viral load from baseline to week 12 was -2.19 log(10) IU/ml overall. The median change in HBV DNA from baseline to weeks 12, 24, 48 and 96 was -2.86, -3.23, -3.75 and -4.03 log(10) IU/ml, respectively. At 48 and 96 weeks, 27/59 (46%) and 38/59 (64%) patients achieved a HBV DNA < 15 IU/ml. The response was independent of baseline LAM therapy or mutations conferring ADV resistance.Conclusions In heavily pretreated patients with a high rate of genotypic resistance, TDF retains significant activity against HBV although this appears diminished in comparison with studies of naive patients.