Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.
J Antimicrob Chemother
; 70(3): 930-40, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25336166
ABSTRACT
OBJECTIVES:
It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART.METHODS:
This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression.RESULTS:
Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (ORâ=â2.75, 95% CIâ=â1.35-5.60, Pâ=â0.005); similar associations were observed for at least one MV versus no NRTI MVs (ORâ=â2.27, 95% CIâ=â0.76-6.77, Pâ=â0.140) and at least one MV versus no NNRTI MVs (ORâ=â2.41, 95% CIâ=â1.12-5.18, Pâ=â0.024). A dose-effect relationship between virological failure and mutational load was found.CONCLUSIONS:
Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
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Inibidores da Transcriptase Reversa
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Terapia Antirretroviral de Alta Atividade
/
Farmacorresistência Viral
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
/
Humans
/
Male
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article