荷兰 HIV 相关急性 HCV 研究中全基因组测序的应用：重点关注传播的抗病毒耐药性。

Use of whole genome sequencing in the Dutch Acute HCV in HIV study: focus on transmitted antiviral resistance.

机构信息

Division of infection and immunity, University College London, London, United Kingdom.

Department of Internal Medicine, Section of Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.

出版信息

Clin Microbiol Infect. 2017 Feb;23(2):123.e1-123.e4. doi: 10.1016/j.cmi.2016.09.018. Epub 2016 Sep 28.

DOI:10.1016/j.cmi.2016.09.018

PMID:27693529

Abstract

OBJECTIVE

Within HIV-positive men having sex with men, the epidemic of hepatitis C virus (HCV) is ongoing. Transmission of resistant variants of HCV after failure of treatment with directly acting antivirals (DAA) could be a major threat to the effectivity of therapy. We determined whether HCV-resistant variants to DAAs were prevalent amongst patients with an acute HCV infection diagnosed in 2013 and 2014 in the Netherlands.

METHODS

Target enrichment for viral nucleic acid separation and deep sequencing were used to recover whole HCV genomes of 50 patients with an acute HCV infection. The genomes were assembled by de novo assembly and analysed for known DAA resistance mutations.

RESULTS

In acute HCV infected treatment-naive patients, the relevant resistance-associated substitutions were Q80K (40%) in NS3/4a, M28V (24%) and Q30H combined with Y93H (2%) in NS5A and M414T (2%) or S556G (2%) in NS5b. Patients whose HCV infection failed to respond to boceprevir, peginterferon and ribavirin therapy developed mutations in NS3 at position T54A and R155K.

CONCLUSIONS

Target enrichment and whole genome sequencing were successfully applied directly on clinical samples from patients with an acute HCV infection.

摘要

目的

在感染 HIV 的男男性行为者中，丙型肝炎病毒 (HCV) 的流行仍在继续。直接作用抗病毒药物 (DAA) 治疗失败后，HCV 耐药变异体的传播可能对治疗效果构成重大威胁。我们确定了在 2013 年和 2014 年荷兰诊断出的急性 HCV 感染患者中，是否存在对 DAA 具有耐药性的 HCV 变异体。

方法

采用靶向富集病毒核酸分离和深度测序技术，从 50 例急性 HCV 感染的患者中分离出完整的 HCV 基因组。通过从头组装对基因组进行组装，并分析已知的 DAA 耐药突变。

结果

在急性 HCV 感染未经治疗的患者中，NS3/4a 中的 Q80K（40%）、NS5A 中的 M28V（24%）和 Q30H 与 Y93H（2%）以及 NS5b 中的 M414T（2%）或 S556G（2%）是相关的耐药相关取代。那些对博赛泼维、聚乙二醇干扰素和利巴韦林联合治疗无反应的 HCV 感染患者在 NS3 位置出现 T54A 和 R155K 突变。