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Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Casadellà M.
  • Santos J.R.
  • Noguera-Julian M.
  • Micán-Rivera R.
  • Domingo P.
  • Antela A.
  • Portilla J.
  • Sanz J.
  • Navarro J.
  • Masiá M.
  • Valcarce-Pardeiro N.
  • Ocampo A.
  • Pérez-Martínez L.
  • Pasquau J.
  • Vivancos M.J.
  • Imaz A.
  • Carmona-Oyaga P.
  • Muñoz-Medina L.
  • Villar-García J.
  • Barrufet P.
  • Paredes R.

Grupos

Abstract

Background: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. Objectives: We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. Methods: Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a = 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants. Results: From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. Conclusions: Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens. © The Author(s) 2020.

Datos de la publicación

ISSN/ISSNe:
0305-7453, 1460-2091

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY  OXFORD UNIV PRESS

Tipo:
Article
Páginas:
3517-3524
PubMed:
32929472
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
2,124 SCImago ℠
Cuartil:
Q1 SCImago ℠

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Keywords

  • Cohort Studies; Drug Resistance, Viral; Genotype; HIV Infections; HIV Integrase; HIV Integrase Inhibitors; HIV-1; Humans; Integrases; Mutation; Prospective Studies; Spain; abacavir; bictegravir; dolutegravir; elvitegravir; emtricitabine; integrase; lamivudine; proteinase; raltegravir; RNA directed DNA polymerase; tenofovir alafenamide; tenofovir disoproxil; integrase; integrase inhibitor; adult; antiretroviral therapy; antiviral resistance; Article; blood sampling; clinical practice; cohort analysis; female; follow up; gene mutation; genotype; human; Human immunodeficiency virus 1 infection; Human immunodeficiency virus infected patient; major clinical study; male; multicenter study; observational study; prevalence; prospective study; Sanger sequencing; Spain; treatment outcome; virus mutation; antiviral resistance; epidemiology; genetics; genotype; Human immunodeficiency virus 1; Human immunodeficiency virus infection; mutation

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