乙型肝炎病毒对核苷类和核苷酸类似物的初级耐药性

StephenW

J Viral Hepat. 2018 Oct 19. doi: 10.1111/jvh.13025. [Epub ahead of print]
Primary Resistance of Hepatitis B Virus to Nucleoside and Nucleotide Analogues.
Chevaliez S1,2, Rodriguez C1,2, Poiteau L1,2, Soulier A1,2, Donati F1,2, Mercier-Darty M1,2, Pioche C3, Leroy V4,5, Brodard V6, Zoulim F7,8, Brouard C3, Larsen C3, Semaille C3, Roudot-Thoraval F9, Pawlotsky JM1,2; Hepatology Reference Centers and Laboratories Network for Chronic Hepatitis B Surveillance.
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Abstract

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. To evaluate the prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses. 232 treatment-naïve patients chronically infected with HBV consecutively referred for the first time to one of French reference centers were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing and the sequences were analyzed. RASs were detected in 25% of treatment-naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by NGS at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response.The presence of preexisting HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used. This article is protected by copyright. All rights reserved.
KEYWORDS:

antiviral treatment; hepatitis B; next-generation sequencing; primary resistance

PMID:
    30339311
DOI:
    10.1111/jvh.13025

StephenW

J病毒肝病。 2018年10月19日doi：10.1111 / jvh.13025。 [提前打印]
乙型肝炎病毒对核苷类和核苷酸类似物的初级耐药性。
Chevaliez S1,2，Rodriguez C1,2，Poiteau L1,2，Soulier A1,2，Donati F1,2，Mercier-Darty M1,2，Pioche C3，Leroy V4,5，Brodard V6，Zoulim F7,8，Brouard C3 ，Larsen C3，Semaille C3，Roudot-Thoraval F9，Pawlotsky JM1,2;用于慢性乙型肝炎监测的肝脏病学参考中心和实验室网络。
作者信息
抽象

靶向乙型肝炎病毒的核苷和核苷酸类似物（NUC）能够在长期施用时选择抗性病毒作为单一疗法。评估NUC治疗基线时耐药相关替代（RAS）和适应性相关替代的患病率及其对治疗反应的影响。首次将连续首次转诊至HBV的232名未接受过治疗的患者首次转诊至法国参考中心之一。通过深度测序对几乎全长的HBV逆转录酶进行测序，并分析序列。在25％未接受过治疗的患者中检测到RAS，通常代表低比例的病毒准种。除了位置80外，已知与目前批准的NUC的HBV抗性相关的所有氨基酸位置或具有增加的抗性变体适应性的氨基酸位置受到影响。拉米夫定，替比夫定和阿德福韦抗性中涉及的位置的RAS是最常检测到的。所有在基线时可通过NGS检测到的RAS患者均符合治疗条件，并使用目前推荐的药物治疗，可获得病毒学应答。如果使用具有高抗药性的强效药物，预先存在的HBV RAS对治疗结果没有影响。本文受版权保护。版权所有。
关键词：

抗病毒治疗;乙型肝炎;新一代测序;初级阻力

结论：
    30339311
DOI：
    10.1111 / jvh.13025