A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) resistance in people treated with entecavir or tenofovir

IF 4 3区医学 Q2 VIROLOGY Journal of Clinical Virology Pub Date : 2024-06-28 DOI:10.1016/j.jcv.2024.105711

Sheila F. Lumley , Marion Delphin , Jolynne F. Mokaya , Cedric C.S. Tan , Emily Martyn , Motswedi Anderson , Ka Chun Li , Elizabeth Waddilove , Gloria Sukali , Louise O. Downs , Khadija Said , Dorcas Okanda , Cori Campbell , Eli Harriss , Yusuke Shimakawa , Philippa C. Matthews

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Abstract

Background

As nucleos/tide analogue (NA) therapy (e.g. entecavir and tenofovir) for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. A systematic review to quantify resistance to these agents has not previously been undertaken.

Methods

We performed a systematic review and random-effects meta-analysis to estimate the risk of HBV resistance to entecavir and tenofovir. We searched nine databases up to 29-Aug-23. We included studies of HBV infection featuring >10 individuals, written in English, reporting treatment ≥48 weeks, with assessment of HBV resistance based on viral sequence data. Data were analysed according to prior exposure history to NA, and choice of NA agent. Analyses were performed in R.

Findings

62 studies involving a total of 12,358 participants were included. For entecavir, in treatment-naive individuals (22 studies; 4326 individuals), resistance increased over time to 0.9 % at ≥5 years (95 %CI 0.1–2.3 %), and resistance was increased in NA-experienced individuals (18 studies; 1112 individuals), to 20.1 % (95 %CI 1.6–50.1 %) at ≥5 years. For tenofovir, pooled resistance risk was 0.0 % at all time points, whether previously NA naive (11 studies; 3778 individuals) or experienced (19 studies; 2059 individuals). There was a lack of consistent definitions, poor global representation and insufficient metadata to support subgroup analysis.

Interpretation

We have generated the first pooled estimates of HBV entecavir and tenofovir resistance over time. HBV resistance to entecavir in treatment-experienced groups in particular may represent a clinical and public health challenge. To date, tenofovir appears to have an excellent resistance profile, but due to data gaps, we caution that existing studies under-estimate the true real-world risk of resistance. Robust prospective data collection is crucial to reduce health inequities and reduce blind-spots in surveillance as treatment is rolled out more widely.

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关于接受恩替卡韦或替诺福韦治疗的人群中乙肝病毒（HBV）耐药风险的系统回顾和荟萃分析。

背景：随着治疗慢性乙型肝炎病毒（HBV）感染的核苷/肽类似物（NA）疗法（如恩替卡韦和替诺福韦）越来越广泛地应用和普及，了解耐药性至关重要。以前从未对这些药物的耐药性进行过量化的系统回顾：我们进行了一项系统综述和随机效应荟萃分析，以估计 HBV 对恩替卡韦和替诺福韦耐药的风险。我们检索了截至 23 年 8 月 29 日的 9 个数据库。我们纳入了以大于 10 人的 HBV 感染为特征、用英语撰写、报告治疗时间≥48 周、根据病毒序列数据评估 HBV 耐药性的研究。数据根据之前的NA暴露史和NA制剂的选择进行分析。分析在 R.Findings 中进行：共纳入 62 项研究，涉及 12,358 名参与者。对于恩替卡韦，随着时间的推移，对恩替卡韦治疗无效者（22 项研究；4326 人）的耐药性在≥5 年时增加到 0.9%（95 %CI 0.1-2.3%），对有 NA 经验者（18 项研究；1112 人）的耐药性在≥5 年时增加到 20.1%（95 %CI 1.6-50.1%）。就替诺福韦而言，在所有时间点，无论是以前未接受过 NA（11 项研究；3778 人）还是有经验（19 项研究；2059 人）的患者，耐药性风险均为 0.0%。这些研究缺乏一致的定义，总体代表性差，元数据不足以支持亚组分析：我们首次对HBV恩替卡韦和替诺福韦的耐药性随时间变化的情况进行了汇总估算。特别是治疗经验丰富的人群对恩替卡韦的耐药性可能是临床和公共卫生方面的一项挑战。迄今为止，替诺福韦的耐药情况似乎很好，但由于数据缺口，我们提醒现有研究低估了真实世界的耐药风险。随着治疗的广泛开展，强有力的前瞻性数据收集对于减少健康不公平现象和减少监测盲点至关重要。

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

Journal of Clinical Virology 医学-病毒学

CiteScore

22.70

自引率

1.10%

发文量

149

审稿时长

24 days

期刊介绍： The Journal of Clinical Virology, an esteemed international publication, serves as the official journal for both the Pan American Society for Clinical Virology and The European Society for Clinical Virology. Dedicated to advancing the understanding of human virology in clinical settings, the Journal of Clinical Virology focuses on disseminating research papers and reviews pertaining to the clinical aspects of virology. Its scope encompasses articles discussing diagnostic methodologies and virus-induced clinical conditions, with an emphasis on practicality and relevance to clinical practice. The journal publishes on topics that include: • new diagnostic technologies • nucleic acid amplification and serologic testing • targeted and metagenomic next-generation sequencing • emerging pandemic viral threats • respiratory viruses • transplant viruses • chronic viral infections • cancer-associated viruses • gastrointestinal viruses • central nervous system viruses • one health (excludes animal health)