1. Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing
- Author
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Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, European Commission, Fundació La Marató de TV3, 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-Matía, Elisa, Martín-Gandul, Cecilia, Carratalà, Jordi, Sabé, Nuria, Niubó, Nuria, Cervera, Carlos, Capón, Alicia, Cervilla, Anna, Santos, Marta, Bodro, Marta, Muñoz García, Patricia, Fariñas, María del Carmen, Antón, Andrés, Aranzamendi Zaldumbide, Maitane, Montejo, Miguel, Pérez-Romero, Pilar, Len, Óscar, Marcos, María Ángeles, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, European Commission, Fundació La Marató de TV3, 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-Matía, Elisa, Martín-Gandul, Cecilia, Carratalà, Jordi, Sabé, Nuria, Niubó, Nuria, Cervera, Carlos, Capón, Alicia, Cervilla, Anna, Santos, Marta, Bodro, Marta, Muñoz García, Patricia, Fariñas, María del Carmen, Antón, Andrés, Aranzamendi Zaldumbide, Maitane, Montejo, Miguel, Pérez-Romero, Pilar, Len, Óscar, and Marcos, María Ángeles
- 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.
- Published
- 2019