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Title: Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing
Author: López Aladid, Rubén
Guiu, Alba
Mosquera, Maria Mar
López Medrano, Francisco
Cofán Pujol, Federico
Linares, Laura
Torre Cisneros, Julián
Vidal, Elisa
Moreno Camacho, Ma. Asunción
Aguado, José María
Cordero, Elisa
Martin Gandul, Cecilia
Carratalà, Jordi
Sabé, Nuria
Niubó, Jordi
Cervera, Carlos
Capón, Alicia
Cervilla, Anna
Santos, Marta
Bodro, Marta
Muñoz, Patricia
Farinas, Maria Carmen
Antón, Andrés
Aranzamendi, Maitane
Montejo, Miguel
Pérez Romero, Pilar
Len, Óscar
Marcos, Ma. Angeles
Keywords: Citomegalovirus
Trasplantament hepàtic
Hepatic transplantation
Issue Date: 18-Jul-2019
Publisher: Public Library of Science (PLoS)
Abstract: Objectives: 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.
Note: Reproducció del document publicat a:
It is part of: PLoS ONE, 2019, vol. 14 , num. 7, p. e0219701
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (ISGlobal)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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