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

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 S...

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Autores: López-Aladid, Rúben, Guiu, Alba, Mosquera, Maria del Mar|||0000-0001-5863-7424, López-Medrano, Francisco, Cofan, Frederic|||0000-0003-4163-9620, Linares González, Laura|||0000-0001-5738-631X, Torre-Cisneros, Julián, Vidal, Elisa, Moreno Camacho, Asunción|||0000-0001-6382-0039, Aguado, José María|||0000-0002-9520-8255, Cordero, Elisa|||0000-0001-7766-7266, Martin-Gandul, Cecilia, Carratalà, Jordi|||0000-0003-3209-2563, Sabé, Núria|||0000-0003-1697-4347, Niubó, Jordi|||0000-0001-9511-0138, Cervera, Carlos, Capón, Alicia, Cervilla, Anna, Santos, Marta, Bodro, Marta|||0000-0002-0520-8279, Munoz, Patricia|||0000-0001-5706-5583, Fariñas, Mª Carmen, Antón Pagarolas, Andrés, 1976-|||0000-0002-1476-0815, Aranzamendi Zaldumbide, Maitane|||0000-0003-2432-7078, Montejo, Miguel, Pérez-Romero, Pilar, Len, Oscar|||0000-0002-1819-3141, Marcos, María Ángeles|||0000-0002-5019-4873
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:223170
Acceso en línea:https://ddd.uab.cat/record/223170
https://dx.doi.org/urn:doi:10.1371/journal.pone.0219701
Access Level:acceso abierto
Palabra clave:Cytomegalovirus
Drug Resistance, Viral
Female
Genes, Viral
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Transplant Recipients
Descripción
Sumario: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.

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