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

Abstract: Objetives The 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. Methods Using 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. Results Among 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 <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). Conclusions NGS 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: PLoS ONE 14 (7)

Editorial: Public Library of Science

 Fecha de publicación: 18/07/2019

Nº de páginas: 13

Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0219701

ISSN: 1932-6203

Url de la publicación: https://doi.org/10.1371/journal.pone.0219701

Autores/as

LÓPEZ-ALADID, RUBÉN

GUIU, ALBA

MOSQUERA, MARÍA MAR

LÓPEZ-MEDRANO, FRANCISCO

COFÁN, FREDERIC

LINARES, LAURA

TORRE-CISNEROS, JULIÁN

VIDAL, ELISA

MORENO, ASUNCIÓN

AGUADO, JOSÉ MARÍA

CORDERO, ELISA

MARTÍN-GANDUL, CECILIA

CARRATALÁ, JORDI

SABÉ, NURIA

NIUBÓ, JORDI

CERVERA, CARLOS

CAPÓN, ALICIA

CERVILLA, ANNA

MARTA SANTOS, MARTA