阿德福韦耐药的乙肝病毒仍然容受到替诺福韦易感

StephenW

http://www.hivandhepatitis.com/hbv-treatment/approved-hbv-drugs/3808-adefovir-resistant-hepatitis-b-virus-can-remain-susceptible-to-tenofovir
Adefovir-resistant Hepatitis B Virus Can Remain Susceptible to Tenofovir
阿德福韦耐药的乙肝病毒仍然容受到替诺福韦易感
   
    Published on Tuesday, 02 October 2012 00:00
    Written by Liz Highleyman



Tenofovir (Viread) continues to be effective for treating chronic hepatitis B patients who have developed resistance to the related drug adefovir (Hepsera), according to a report in the August 14, 2012, online edition of Antiviral Therapy.

Several nucleoside analogs are active against hepatitis B virus (HBV), but the virus can rapidly develop resistance, compromising long-term treatment effectiveness. One of the most effective current drugs, tenofovir, is a nucleotide analog that differs from most earlier agents. However, it is related to another approved nucleotide, adefovir, raising the possibility of cross-resistance.

Florian van Bömmel from the University of Leipzig and colleagues assessed the clinical relevance of HBV polymerase gene variants in people with genotypic resistance to adefovir -- namely the rtN236T and/or rtA181V/T mutations -- who were later treated with tenofovir. In vitro studies show that HBV mutations selected by adefovir confer cross-resistance to tenofovir, the study authors noted as background, but this may not significantly affect tenofovir susceptibility.

The analysis included 10 chronic hepatitis B patients. All but 1 were men, the mean age was 47 years, and 60% were hepatitis B "e" antigen (HBeAg) positive. People with hepatitis C or HIV coinfection were excluded. Participants had experienced virological breakthrough during adefovir treatment associated with the rtN236T and/or rtA181T/V mutations and were later treated with tenofovir.

The researchers analyzed polymerase gene variants during up to 24 months of consecutive tenofovir monotherapy using population sequencing, line probe assays, and clonal analysis.

Results

    In all patients, switching to tenofovir resulted in a continuous reduction in HBV viral load.
    HBV DNA levels fell from a median 7.6 to 3.3 log copies/mL, although viral load remained > 400 copies/mL in 7 patients at 12 months.
    Adefovir resistance mutations remained detectable throughout the entire observation period in most patients.
    Apart from an M204Q mutation in 1 sample, no new tenofovir-associated HBV polymerase gene mutations were identified.
    In 2 participants with continued low-level viral load after 18 weeks on tenofovir, adding lamivudine (3TC or Epivir) led to complete response within a few weeks.

Based on these findings, the study authors concluded, "Adefovir-resistant HBV variants may further become selected during tenofovir treatment, however they cause only a mild decrease in tenofovir susceptibility."

10/2/12

Reference

F Bömmel, J Trojan, K Deterding, et al. Evolution of adefovir-resistant HBV polymerase gene variants after switching to tenofovir disoproxil fumarate monotherapy. Antiviral Therapy 17:1049-1058. August 14, 2012 (Epub ahead of print).

StephenW

阿德福韦耐药的乙肝病毒仍然受到替诺福韦易感



类别：核准HBV药物
    发表于2012年10月2日（星期二）00:00
    作者：利兹Highleyman的



替诺福韦（VIREAD的）仍然是有效的治疗慢性乙型肝炎患者产生抗药性的相关药物阿德福韦（阿德福韦酯），根据2012年8月14日的一份报告中，网络版的抗病毒治疗。

几个核苷类似物，对乙型肝炎病毒（HBV），但该病毒可以迅速产生耐药性，影响长期治疗效果。电流的最有效的药物，替诺福韦，之一是一种核苷酸类似物，不同于大多数早期剂。然而，它被有关的其他经批准的碱基，阿德福韦，提高的可能性的交叉耐药性。
弗洛里安·范博梅尔从莱比锡大学和他的同事评估的临床意义HBV聚合酶基因变异与基因型耐药阿德福韦 - 即rtN236T和/或rtA181V / T突变 - 谁是替诺福韦治疗的人。在体外研究表明，HBV突变选择阿德福韦赋予的交叉耐药性，以替诺福韦，该研究的作者指出作为背景，但是这可能不会显着影响替诺福韦敏感性。

该分析包括10例慢性乙肝患者。全部只有1名是男性，平均年龄为47岁，60％为B型肝炎的“e”抗原（HBeAg）阳性。 C型肝炎或HIV合并感染的人被排除在外。与会者阿德福韦治疗与rtN236T和/或rtA181T / V突变，后来替诺福韦治疗过程中出现病毒学突破。

研究人员分析了聚合酶基因变异体在最多24个月的连续替诺福韦单药治疗，使用人口测序，线性探针检测，克隆分析。

结果

    在所有患者中，切换到替诺福韦导致HBV病毒载量持续减少。
    HBV DNA水平中位数下降至7.6至3.3日志拷贝/毫升，虽然病毒载量> 400拷贝/ ml，7例在12个月保持。
    阿德福韦耐药突变的检测，大多数患者在整个观察期。
    除了从一个M204Q的突变在1个样品外，没有新的替诺福韦相关的HBV聚合酶基因突变进行了鉴定。
    上替诺福韦18周后，与持续的低级别的病毒载量在2人参加，加入拉米夫定（3TC或博路定），在几个星期内完成响应。

基于这些发现，研究人员得出结论，“阿德福韦耐药的HBV变异可能会进一步成为替诺福韦治疗期间选择，但他们在替诺福韦敏感性下降导致只有轻微的。”

12年10月2日

参考

F，J范博梅尔木马，K Deterding，等。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。抗病毒治疗17:1049-1058。 2012年8月14日（EPUB的提前打印）。

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