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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
Notes:	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.
Subject(s):	-Citomegalovirus -Trasplantament hepàtic -Cytomegaloviruses -Hepatic transplantation
Rights:	cc by (c) López Aladid et al., 2019 http://creativecommons.org/licenses/by/3.0/es/
Document type:	Article Article - Published version
Published by:	Public Library of Science (PLoS)
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