Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

IF 8.2 1区医学 Q1 IMMUNOLOGY

Clinical Infectious Diseases Pub Date : 2024-12-17 DOI:10.1093/cid/ciae431

Seth Inzaule, Philippa Easterbrook, Ashley Latona, Nathan P Ford, William Irving, Philippa C Matthews, Marco Vitoria, Chris Duncombe, Amalia Giron, Suzanne McCluskey, Olufunmilayo Lesi, Serge Tchamgoue, Rachel Halford, Danjuma Adda, Emma Thomson, Geoff Dusheiko, Michael R Jordan

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引用次数: 0

Abstract

Background: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy.

Methods: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis.

Results: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors.

Discussion: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

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慢性丙型肝炎感染者在首次或再次接受泛基因型直接作用抗病毒药物治疗后，耐药性相关替代物的流行率：系统回顾和元分析》。

背景：直接作用抗病毒药物（DAA）短疗程、治愈性治疗的出现为到 2030 年全球消除丙型肝炎病毒（HCV）感染带来了希望。2%-12%的接受直接作用抗病毒药物治疗的患者会出现病毒学失败，这可能是由先前存在的多态性预示的，也可能是在治疗过程中选择耐药变体导致的：我们进行了一项系统性回顾，以评估首次或再次接受泛基因型DAA方案治疗后出现病毒学失败的慢性丙型肝炎感染者中HCV耐药相关变异（RAS）的发生率。我们纳入了 2014 年 1 月至 2023 年 7 月间发表的 34 项和 22 项评估病毒学失败患者 RAS 的研究。采用随机效应荟萃分析法估算了汇总的RAS患病率：索非布韦/韦帕他韦的RAS在初始DAA治疗后病毒学失败者中的合计流行率为78.0%（95%置信区间[CI]：62.0-92.0），索非布韦/达卡他韦为81.0%（95% CI：67.0-93.0），格列卡普瑞韦/匹布伦达韦为79.0%（95% CI：70.0-87.0），其中NS5A抑制剂的耐药流行率较高。在接受再治疗方案后出现病毒学失败的患者中，索非布韦/韦帕他韦/沃西帕韦的RAS出现率为93.0%（95% CI：83.0-99.0），格列卡普瑞韦/匹布伦达韦的RAS出现率为100%（95% CI：92.0-100），RAS对NS5A抑制剂产生耐药性：讨论：在使用泛基因型 DAA 方案进行初始治疗或再治疗后出现病毒学失败的少数患者中，至少有很高比例的患者存在 1 种 RAS。有必要对DAA相关耐药性进行持续监测，评估其产生的风险因素和临床影响，为再治疗的最佳实践策略提供依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Infectious Diseases 医学-传染病学

CiteScore

25.00

自引率

2.50%

发文量

900

审稿时长

3 months

期刊介绍： Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.