Minority resistant HIV-1 variants and the response to first-line NNRTI therapy.
J Clin Virol
; 62: 20-4, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25542465
ABSTRACT
BACKGROUND:
The presence of low-frequency HIV-1 variants with mutations making them resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) could influence the virological response to first-line NNRTI therapy.OBJECTIVES:
This study was designed to describe the proportions and quantities of NRTI and NNRTI-resistant variants in patients with successful first-line NNRTI therapy. STUDYDESIGN:
We evaluated the presence of drug-resistance mutations (DRMs) prior to treatment initiation in 131 naive chronically HIV-1-infected patients initiating NNRTI-based first-line therapy. DRMs were detected by ultradeep pyrosequencing (UDPS) on a GS Junior instrument (Roche).RESULTS:
The mean HIV RNA concentration was 4.78 ± 0.74 log copies/mL and the mean CD4 cell count was 368 ± 184 CD4 cells/mm(3). Patients were mainly infected with subtype B (68%) and 96% were treated with efavirenz. The sensitivity threshold for each mutation was 0.13-1.05% for 2000 reads. Major NRTI-resistant or NNRTI-resistant mutations were detected in 40 patients (33.6%). The median frequency of major NRTI-resistant mutations was 1.37% [IQR 0.39-84.1], i.e. a median of 556 copies/mL [IQR 123-37,553]. The median frequency of major NNRTI-resistant DRMs was 0.78% [IQR 0.67-7.06], i.e. a median of 715 copies/mL [IQR 391-3452]. The genotypic susceptibility score (GSS) of 9 (7.3%) patients with mutations to given treatment detected by UDPS was 1.5 or 2.CONCLUSIONS:
First-line NNRTI-based treatment can produce virological success in naïve HIV-1-infected patients harboring low-frequency DRMs representing <1% of the viral quasispecies. Further studies are needed to determine the clinical cut-off of low-frequency resistant variants associated to virological failure.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Infecções por HIV
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HIV-1
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Inibidores da Transcriptase Reversa
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Farmacorresistência Viral
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article