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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.
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
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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
MARIA DEL CARMEN FARIÑAS ALVAREZ
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