Results from the French Cohorts 2006-2010 and OrphaVic (NCTNCT02067169) indicates that fifty percent of graft failures in renal recipients infected by HCMV after treatment with Ganciclovir cannot be attributed to a resistance mutation detected by SANGER sequencing genotyping. The hypothesis is that the mutated viral population in below the method's detection threshold of 20% of viral population. The objective of this retrospective study was to assess the capacity of new-generation sequencing (NGS, Ion Torrent) to diagnose these mutations. This study applied to fourteen samples from non-responding subjects, without UL97 and UL54 gene mutations detected by SANGER genotyping and twenty seven control samples prior to any antiviral treatment at therapeutic doses. In the fourteen samples, no known resistance mutations in fewer than 20% of viral population were detected by NGS. However, new previously undescribed mutations were detected in seven of them. Viral isolates with only polymorphic mutations present were detected in three samples. The last four presented resistance mutations in more than 20% in the viral population, which should have been detected by the SANGER method, confirmed retrospectively. In the control samples no mutations present in fewer than 20% of the viral population were identified. This study demonstrates that NGS sequencing enables the detection of new mutations undetectable by SANGER method in patients not responding to treatment. The impact of these new mutations is still to be determined.

This work has been perfomed on behalf of the CMV resist group virologists and nephrologists from Toulouse (C mengelle, N Kamar), Bordeaux (I Garrigue, P Merville), Clermont-Ferrand (C Archimbaud , and nephrology dept), Tours (C Gaudy , m Buchler), Limoges (JP Rerolle), Strasbourg (S Caillard, S Fafi-Kremer), Besançon (A Coaquette, D Ducloux), Saint Etienne (S Pillet, c Mariat), Grenoble (R Germi, B Janbon).

CITATION INFORMATION: Danthu C, Gomes-Mayeras M, Andouard D, Munteanu E, Moulinas R, Ligat G, Hantz S, Rerolle J, Garnier F, Essig M, Alain S. Contribution of New Generation Sequencing to CMV Resistance Analysis in Renal Transplant Recipients (on Behalf of the CMV Resist Group). Am J Transplant. 2017;17 (suppl 3).

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