Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing.
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ID: 27141
2019
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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.
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| Authors | López-Aladid, Rubén;Guiu, Alba;Mosquera, Maria Mar;López-Medrano, Francisco;Cofán, Frederic;Linares, Laura;Torre-Cisneros, Julián;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;Pérez-Romero, Pilar;Len, Oscar;Marcos, Maria Ángeles; |
| Journal | PloS one |
| Year | 2019 |
| DOI |
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| Keywords | Keywords not found |
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