Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/8705
Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing
López-Aladid, Rubén | Guiu, Alba | Mosquera Gutierrez, Maria del Mar ISCIII | López-Medrano, Francisco | Cofán, Frederic | Linares, Laura | Torre-Cisneros, Julian | Vidal, Elisa | Moreno, Asunción | Aguado, Jose María | Cordero, Elisa | Martin-Gandul, Cecilia | Carratalá, Jordi | Sabé, Nuria | Niubó, Jordi | Cervera, Carlos | Capón, Alicia | Cervilla, Anna | Santos, Marta | Bodro, Marta | Muñoz, Patricia | Fariñas, Maria Carmen | Antón, Andrés | Aranzamendi, Maitane | Montejo, Miguel | Perez-Romero, Pilar ISCIII | Len, Oscar | Marcos, Maria Ángeles
PLoS One. 2019 Jul 18;14(7):e0219701.
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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