Titre :

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

Auteur(s) :

Alidjinou, Enagnon Kazali [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Coulon, Pauline [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Tetart, Macha [Auteur]
Centre Hospitalier de Tourcoing
Guigon, Aurelie [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Diarra, Ava [Auteur]
Centre Hospitalier de Tourcoing
Aissi, Emmanuelle [Auteur]
Centre Hospitalier de Lens
Bazus, Hélène [Auteur]
Centre Hospitalier de Lens
Derdour, Vincent [Auteur]
Centre Hospitalier de Tourcoing
Meybeck, Agnès [Auteur]
Centre Hospitalier de Tourcoing
Viget, Nathalie [Auteur]
Centre Hospitalier de Tourcoing
Hober, Didier [Auteur]
Laboratoire de virologie - ULR 3610
Bocket, Laurence [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Robineau, Olivier [Auteur]
Centre Hospitalier de Tourcoing

Titre de la revue :

Journal of Antimicrobial Chemotherapy

Nom court de la revue :

J Antimicrob Chemother

Pagination :

dkaf016

Éditeur :

Oxford University Press (OUP)

Date de publication :

2025-01-24

ISSN :

1460-2091

Mot(s)-clé(s) en anglais :

mutation
drug resistance
dna
hiv-1
plasma
proviruses
guidelines
genotype determination
massively-parallel genome sequencing
viral suppression

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

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. ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• Laboratoire de virologie - ULR 3610

Date de dépôt :

2025-03-15T22:05:01Z
2025-03-28T09:33:59Z