慢性丙型肝炎感染患者以及初次或再次使用泛基因型直接抗病毒药物治疗后病毒学失败患者中耐药相关替代位点的流行率：一项系统评价和荟萃分析
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.
作者信息
Inzaule Seth, Easterbrook Philippa, Latona Ashley, Ford Nathan P, Irving William, Matthews Philippa C, Vitoria Marco, Duncombe Chris, Giron Amalia, McCluskey Suzanne, Lesi Olufunmilayo, Tchamgoue Serge, Halford Rachel, Adda Danjuma, Thomson Emma, Dusheiko Geoff, Jordan Michael R
机构信息
Amsterdam Institute for Global Health and Development, and Department of Global Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization, Geneva, Switzerland.
出版信息
Clin Infect Dis. 2024 Dec 17;79(6):1437-1446. doi: 10.1093/cid/ciae431.
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.
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。在接受治愈性DAA治疗的患者中，2%-12%会出现病毒学失败，这可能由预先存在的多态性预示，或由治疗期间耐药变异体的选择导致。
方法
我们进行了一项系统评价，以评估在接受泛基因型DAA初始治疗或再治疗后出现病毒学失败的慢性丙型肝炎感染个体中，HCV耐药相关替代（RAS）的患病率。我们纳入了2014年1月至2023年7月发表的34项和22项评估病毒学失败患者RAS的研究。使用随机效应荟萃分析估计合并的RAS患病率。
结果
在接受索磷布韦/维帕他韦初始DAA治疗后出现病毒学失败的患者中，RAS的合并患病率为78.0%（95%置信区间[CI]：62.0-92.0），索磷布韦/达卡他韦为81.0%（95%CI：67.0-93.0），格卡瑞韦/哌仑他韦为79.0%（95%CI：70.0-87.0），对NS5A抑制剂的耐药率较高。在接受再治疗方案后出现病毒学失败的患者中，索磷布韦/维帕他韦/伏西瑞韦的RAS患病率为93.0%（95%CI：83.0-99.0），格卡瑞韦/哌仑他韦为100%（95%CI：92.0-100），耐药由对NS5A抑制剂的RAS驱动。
讨论
在接受泛基因型DAA初始治疗或再治疗后出现病毒学失败的少数个体中，至少1种RAS的比例很高。需要持续监测DAA相关耐药性，以评估其发生的风险因素和临床影响，为再治疗的最佳实践策略提供信息。
Zotero 插件