Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana.
AIDS
; 35(15): 2413-2421, 2021 12 01.
Article
em En
| MEDLINE
| ID: mdl-34324451
ABSTRACT
OBJECTIVE:
To describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants.DESIGN:
The Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs).METHODOLOGY:
We analyzed 257 near-HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96âweeks. DRMs were identified using the Stanford HIV Drug Resistance Database.RESULTS:
In 27 infants, median PBMC HIV-1 proviral load was 492âcopies/ml [IQR 78-1246âcopies/ml] at a median of 2âdays (range 1-32); 18 (66.7%) had no DRMs detected; six (22.2%) had DRMs detected in defective DNA only, and three (11.1%) had DRMs in both defective and intact DNA (Pâ=â0.09). A total of 60 of 151 (37.7%) defective sequences had at least one DRM 31.8% NNRTI, 15.2% NRTI, 5.3% protease inhibitor, and 15.5% INSTI-associated mutations. In intact sequences, 33 of 106 (31.1%) had at least 1 DRM 29.2% NNRTI, 7.5% NRTI, 0.9% protease inhibitor, and no INSTI-associated mutations. For all three infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion.CONCLUSION:
Defective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Fármacos Anti-HIV
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Africa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article