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首页> 外文期刊>Infection and Drug Resistance >Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus
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Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus

机译：在感染了丙型肝炎病毒的血液透析和肾移植患者中，耐药性替代直接作用抗病毒药的流行

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Background: Direct-acting antiviral agents (DAAs) permit the use of interferon (IFN)-free regimens to treat hepatitis C (HCV) in patients with chronic kidney disease (CKD) on hemodialysis (HD) or renal transplant (RTx) recipients, with excellent response rates and safety. However, the occurrence of basal or therapy-induced resistance-associated substitutions (RASs) to DAAs can result in treatment failure. The aim of this study was to estimate the prevalence of RASs to NS3A, NS5A and NS5B inhibitors, and particularly the Q80K polymorphism, in CKD patients on HD and RTx recipients infected with HCV. Patients and methods: HD and RTx patients infected with HCV-genotype 1 (GT1) were subjected to sequencing of the NS3, NS5A and NS5B regions. Results: Direct sequencing of NS3 protease, NS5A and NS5B was performed in 76 patients (HD, n=37; RTx, n=39). The overall prevalence of RASs was 38.2%, but only 5.3% of the patients had mutations in more than one region. Substitutions were detected in NS3A (17.8%), NS5A (21.9%) and NS5B (8.4%). Q80K was detected in 1.5 % of the patients. Highly inhibitory RASs were uncommon (L31M, 2.6%; L159F+C316N, 2.6%). RASs were more prevalent in HCV-GT1a (42.9%) than in HCV-GT1b (32.4%), P =0.35. RASs were detected in 52.4% of treatment-naive patients and 27.8% of peg-IFN/ribavirin-experienced patients ( P =0.12). The presence of RASs was associated with time of RTx ( P =0.01). Conclusion: The Q80K polymorphism was uncommon in our sample of HD and RTx patients. Despite the high prevalence of naturally occurring RASs, most of the substitutions detected were associated with a low level of resistance to DAAs.
机译：背景：直接作用抗病毒药物（DAA）允许使用无干扰素（IFN）的方案来治疗接受血液透析（HD）或肾移植（RTx）接受治疗的慢性肾脏病（CKD）患者的丙型肝炎（HCV），具有出色的响应率和安全性。但是，对DAA的基础或治疗诱导的耐药相关替代（RAS）的发生可能导致治疗失败。这项研究的目的是评估在感染了HCV的HDD和RTx受体的CKD患者中，RASs对NS3A，NS5A和NS5B抑制剂的流行，特别是Q80K多态性。患者和方法：对感染HCV基因型1（GT1）的HD和RTx患者进行NS3，NS5A和NS5B区域测序。结果：对76例患者进行了NS3蛋白酶，NS5A和NS5B的直接测序（HD，n = 37; RTx，n = 39）。 RASs的总体患病率为38.2％，但只有5.3％的患者在一个以上区域发生了突变。在NS3A（17.8％），NS5A（21.9％）和NS5B（8.4％）中检测到替代。在1.5％的患者中检测到Q80K。高度抑制性的RAS不常见（L31M，2.6％; L159F + C316N，2.6％）。 RAS在HCV-GT1a（42.9％）中比在HCV-GT1b（32.4％）中更为普遍，P = 0.35。在未治疗的患者中有52.4％的患者检测到RASs，在接受过peg-IFN /利巴韦林治疗的患者中有27.8％的患者检测到RAS（P = 0.12）。 RASs的存在与RTx的时间有关（P = 0.01）。结论：我们的HD和RTx患者样本中Q80K多态性并不常见。尽管天然存在的RAS的患病率很高，但检测到的大多数替代都与低水平的DAA耐药性有关。

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