Defective HIV-1 DNA pol sequences are not associated with HIV-1 DNA levels and drive most APOBEC-context drug resistance mutations.

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES
Enagnon Kazali Alidjinou, Pauline Coulon, Macha Tetart, Aurélie Guigon, Ava Diarra, Emmanuelle Aissi, Hélène Bazus, Vincent Derdour, Agnès Meybeck, Nathalie Viget, Didier Hober, Laurence Bocket, Olivier Robineau
{"title":"Defective HIV-1 DNA pol sequences are not associated with HIV-1 DNA levels and drive most APOBEC-context drug resistance mutations.","authors":"Enagnon Kazali Alidjinou, Pauline Coulon, Macha Tetart, Aurélie Guigon, Ava Diarra, Emmanuelle Aissi, Hélène Bazus, Vincent Derdour, Agnès Meybeck, Nathalie Viget, Didier Hober, Laurence Bocket, Olivier Robineau","doi":"10.1093/jac/dkaf016","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The specificity of HIV-1 DNA genotypic resistance tests (GRTs) is hampered by the detection of the APOBEC-context drug resistance mutations (AC DRMs), usually harboured by replication-incompetent proviruses. We sought factors associated with defective sequences in the HIV-1 pol region. In addition, AC DRMs and their link with defective sequences were investigated.</p><p><strong>Methods: </strong>We included ART-treated patients with viral suppression or plasma viral load (VL) lower than 200 copies/mL, who underwent HIV-1 DNA genotyping, with successful sequencing of protease (PR), reverse transcriptase (RT) and integrase (IN) regions. Sequencing was performed using either the Sanger method or the Sentosa® NGS approach with a 20% cut-off. All hypermutated sequences and/or those containing at least one stop codon were considered defective.</p><p><strong>Results: </strong>A total of 613 HIV-1 DNA GRTs were analysed. Defective sequences were identified for 186 samples (30.3%) including 65 PR sequences, 92 RT sequences and 65 IN sequences. No association, including HIV-1 DNA levels, was found with the detection of defective pol sequences. A total of 226 AC DRMs were recorded in all sequences. Most of these mutations (78%) were harboured by defective sequences. AC DRMs did not emerge in the plasma viral population, and likely do not impact the virological response to ART.</p><p><strong>Conclusions: </strong>Defectives pol sequences were not associated with HIV-1 DNA levels and harboured most of the AC DRMs. Such mutations likely have no clinical impact, and should not be reported in routine practice. Consensus guidelines for reporting HIV-1 DNA GRTs are needed, especially for the assessment and management of AC DRMs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Antimicrobial Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jac/dkaf016","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: The specificity of HIV-1 DNA genotypic resistance tests (GRTs) is hampered by the detection of the APOBEC-context drug resistance mutations (AC DRMs), usually harboured by replication-incompetent proviruses. We sought factors associated with defective sequences in the HIV-1 pol region. In addition, AC DRMs and their link with defective sequences were investigated.

Methods: We included ART-treated patients with viral suppression or plasma viral load (VL) lower than 200 copies/mL, who underwent HIV-1 DNA genotyping, with successful sequencing of protease (PR), reverse transcriptase (RT) and integrase (IN) regions. Sequencing was performed using either the Sanger method or the Sentosa® NGS approach with a 20% cut-off. All hypermutated sequences and/or those containing at least one stop codon were considered defective.

Results: A total of 613 HIV-1 DNA GRTs were analysed. Defective sequences were identified for 186 samples (30.3%) including 65 PR sequences, 92 RT sequences and 65 IN sequences. No association, including HIV-1 DNA levels, was found with the detection of defective pol sequences. A total of 226 AC DRMs were recorded in all sequences. Most of these mutations (78%) were harboured by defective sequences. AC DRMs did not emerge in the plasma viral population, and likely do not impact the virological response to ART.

Conclusions: Defectives pol sequences were not associated with HIV-1 DNA levels and harboured most of the AC DRMs. Such mutations likely have no clinical impact, and should not be reported in routine practice. Consensus guidelines for reporting HIV-1 DNA GRTs are needed, especially for the assessment and management of AC DRMs.

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.20
自引率
5.80%
发文量
423
审稿时长
2-4 weeks
期刊介绍: The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信