PLoS ONE (Jan 2019)

Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing.

  • Rubén López-Aladid,
  • Alba Guiu,
  • Maria Mar Mosquera,
  • Francisco López-Medrano,
  • Frederic Cofán,
  • Laura Linares,
  • Julián Torre-Cisneros,
  • Elisa Vidal,
  • Asunción Moreno,
  • Jose María Aguado,
  • Elisa Cordero,
  • Cecilia Martin-Gandul,
  • Jordi Carratalá,
  • Nuria Sabé,
  • Jordi Niubó,
  • Carlos Cervera,
  • Alicia Capón,
  • Anna Cervilla,
  • Marta Santos,
  • Marta Bodro,
  • Patricia Muñoz,
  • Maria Carmen Fariñas,
  • Andrés Antón,
  • Maitane Aranzamendi,
  • Miguel Montejo,
  • Pilar Pérez-Romero,
  • Oscar Len,
  • Maria Ángeles Marcos

DOI
https://doi.org/10.1371/journal.pone.0219701
Journal volume & issue
Vol. 14, no. 7
p. e0219701

Abstract

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ObjetivesThe aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance.MethodsUsing Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016.ResultsAmong 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in ConclusionsNGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.