Proportion of APOBEC3-induced defective HIV DNA after 1â
year of dolutegravirâ+âlamivudine simplification in the ANRS 167 LAMIDOL trial.
J Antimicrob Chemother
; 78(12): 2995-3002, 2023 12 01.
Article
em En
| MEDLINE
| ID: mdl-37930812
ABSTRACT
BACKGROUND:
Hypermutated viruses induced by APOBEC3 (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3) proteins comprise some of the defective viruses in the HIV reservoir. Here, we assessed the proportion of APOBEC3-induced defective proviruses in HIV-positive patients before and after receiving dolutegravirâ+âlamivudine dual therapy.METHODS:
PBMCs of virologically suppressed patients enrolled in the ANRS 167 LAMIDOL trial, evaluating a switch from triple therapy to dolutegravirâ+âlamivudine, were collected 8â weeks before (W-8) and 48â weeks after (W48) dual-therapy initiation. The Vif and RT regions were subject to next-generation sequencing. Bioinformatic algorithms were developed to identify APOBEC3-defective sequences and APOBEC3-related drug resistance mutations (APOMuts). All hypermutated sequences and those containing at least one stop codon were considered as defective.RESULTS:
One hundred and four patients were enrolled (median virological suppression duration 4.2â years; IQR 2.0-9.1). Proviral defective reads at W-8 and W48 were detected in Vif in 22% and 29% of patients, respectively, and in RT in 38% and 42% of patients, respectively. At least one APOMut was present in proviruses of 27% and 38% of patients at W-8 and W48, respectively. The ratio of APOMuts/number of potential APOMut sites was significantly higher at W48 (16.5%) than at W-8 (9.8%, Pâ=â0.007). The presence of APOBEC3-defective viruses at W-8 was not associated with HIV total DNA level, nor with the third drug class received prior to switching to dolutegravirâ+âlamivudine, nor with the duration of virological suppression.CONCLUSIONS:
Whereas no significant change in the proportion of patients with APOBEC3-defective proviruses was evidenced after 1â year of dolutegravirâ+âlamivudine maintenance, enrichment in APOMuts was observed. Further longer-term studies are needed to assess the other forms of defective viruses with dual-therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Fármacos Anti-HIV
Limite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França