Evolution of ADV-resistant variants after switching to TDF

肝胆速递

Antivir Ther. 2012 Aug 14. doi: 10.3851/IMP2307. [Epub ahead of print]
Evolution of adefovir-resistant HBV polymerase gene variants after switching to tenofovir disoproxil fumarate monotherapy.
van Bömmel F, Trojan J, Deterding K, Wedemeyer H, Wasmuth HE, Hüppe D, Möller B, Bock FJ, Feucht HH, Berg T.
Source

Department of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany. [email protected].
Abstract
BACKGROUND:

Tenofovir disoproxil fumarate (TDF), an acyclic nucleotide analogue was shown to be effective in many HBV-infected patients with resistance to adefovir dipivoxil (ADV). This observation is intriguing because in vitro studies show that HBV mutations selected by ADV confer cross-resistance to TDF. To assess the clinical relevance of this cross-resistance, we studied the evolution of HBV polymerase gene variants in patients with genotypic resistance against ADV (rtN236T and/or rtA181V/T) during TDF treatment.
METHODS:

In 10 HBV-monoinfected patients (9 male, mean age 47 ±11 [range 27-67] years, 6 hepatitis B e antigen-positive) with virological breakthrough during ADV treatment associated with the mutations rtN236T and/or rtA181T/V, HBV polymerase gene variants were studied during up to 24 months of consecutive monotherapy with TDF by population sequencing, line probe assay and clonal analysis.
RESULTS:

In all patients, switching to TDF resulted in a continuous reduction of HBV DNA from a median of 7.6 (4.6-9.4) log(10) copies/ml to 3.3 (2-5) log(10) copies/ml, remaining in 7 patients >400 copies/ml at 12 months. ADV-resistance mutations remained detectable throughout the whole observation period in most patients. Apart from an M204Q mutation in one sample, no new HBV polymerase gene mutations were found. In two patients with low level viraemia after 72 weeks of TDF, adding lamivudine led to a complete response within a few weeks.
CONCLUSIONS:

ADV-resistant HBV variants may further become selected during TDF treatment, however they cause only a mild decrease in TDF susceptibility.

肝胆速递

Antiviral疗法2012年8月14日。 DOI：10.3851/IMP2307。 [EPUB的提前打印]
切换到富马酸替诺福韦酯单药治疗后，阿德福韦耐药HBV聚合酶基因变异体的演变。
魏德迈ĤDeterding K表，木马J，F，范博梅尔，Wasmuth HE，许佩ð，马勒乙，博克FJ，Feucht的HH，伯格T.
源

的杂志，诊所，莱比锡，德国莱比锡大学医院胃肠病学和风湿病。 florian.vanboemmel @ medizin.uni leipzig.de。
抽象
背景：

替诺福韦disoproxil富马酸（TDF），无环核苷类似物被证明是有效地在许多HBV感染患者抗阿德福韦酯（ADV）。这是耐人寻味的，因为在体外研究表明，ADV赋予TDF交叉耐药性HBV突变选择观察。为了评估这个交叉耐药性的临床相关性，我们研究了在TDF治疗的患者对ADV（rtN236T和/或rtA181V / T）基因型耐药的HBV聚合酶基因变异在进化。
方法：

在10的HBV-的monoinfected例（9男，平均年龄47±11 [范围27-67岁，B型肝炎e抗原阳性）与ADV治疗过程中与突变的rtN236T和/或rtA181T / V，HBV相关的病毒学突破聚合酶基因变异体进行了研究时至24个月的连续单药治疗与TDF的人口测序，线性探针检测和克隆分析。
结果：

在所有患者中，切换到TDF在不断降低HBV DNA中位数为7.6（4.6-9.4）日志（10）拷贝/毫升至3.3（2-5）日志（10）拷贝/毫升，其余7患者> 400拷贝/ ml，在12个月。 ADV耐药突变检测，大多数患者在整个观察期。除了从一个M204Q的突变中的一个样本外，没有新的HBV聚合酶基因突变被发现。在两个水平低病毒血症患者TDF 72周后，加入拉米夫定导致了一个完整的响应，在几个星期内。
结论：

ADV耐药HBV变异可能会进一步成为TDF治疗期间选择，但是它们会导致TDF敏感性只有轻微下降。

咬牙硬挺

阿德耐药患者的福音，未生育女性患者的福音