External quality assessment for herpes simplex virus Drug Resistance Testing: A French Feasibility Study

No: 1668 Presentation at ESCV 2015: Poster 2 External quality assessment for herpes simplex virus Drug Resistance Testing: A French Feasibility Study S. Burrel1,∗, N. Fidouh2, E. Frobert3, F. Damond2, F. Morfin3, D. Boutolleau1 1 AP-HP, Hopitaux Universitaires Pitie-Salpetriere – Charles Foix, Service de Virologie and Sorbonne University, France 2 AP-HP, Hopitaux Universitaires Bichat-Claude Bernard, Service de Virologie, Paris, France 3 Hospices Civils de Lyon, Laboratoire de virologie Est, Centre de Biologie et de Pathologie Est, Lyon, France Background: Among immunocompromised patients, herpes simplex virus (HSV) infections are associated to morbidity and mortality, and the therapeutic management may be challenging with the emergence of HSV resistance to currently used antivirals (i.e., acyclovir [ACV] and foscanet [FOS]). The prevalence of HSV infections caused by ACV-resistant isolates in immunocompromised patients ranges from 3.5% to 11%. The diagnosis of HSV drug resistance can be performed using phenotypic (measurement of the antiviral 50% effective concentration [EC50]) and/or genotypic (sequencing of UL23 thymidine kinase and UL30 DNA polymerase genes) assays. However, the standardization of these methods is required in the era of quality assurance. In an attempt to compare the results for HSV drug resistance between laboratories, an external quality assessment (EQA) pilot study was organized in France. Methods: In 2014 and 2015, three French virology laboratories participated to this (EQA) pilot study. Each year, one laboratory coordinator prepared and sent to the two other participating laboratories a blinded EQA panel of 3 samples consisting in HSV clinical isolates, previously characterized for drug susceptibility to ACV and FOS, or HSV-negative samples. The EQA panel was thereafter analyzed phenotypically (2014 and 2015) and genotypically (2015 only) by the three laboratories according to their local routine procedures. Participants were instructed to describe the methodologies of their assays, and to report the following results: EC50 for ACVandFOS,mutations identifiedwithinUL23andUL30genes, and the corresponding interpretations (i.e., susceptibility or resistance to antivirals). Results were asked to be reported to the laboratory coordinator within 4 weeks of the receipt of the panels. Results: Laboratory-developed techniques were used by all three participants for both phenotypic and genotypic antiviral resistance assays. In 2014, EQA panel consisted of one drugsensitive HSV-2 isolate, one ACV-resistant HSV-2 isolate, and one HSV-negative sample. In 2015, EQA panel included one drugsensitive HSV-1 isolate, one ACV-resistant HSV-1 isolate, and one ACV-resistantHSV-2 isolate. Thedeadline for submitting the results was met by all laboratories. As a whole, all phenotypic and genotypic results were 100% concordant for both EQA studies. Conclusions: The results from this EQA pilot study for assessing the proficiency of laboratories in the detection of HSV drug resistance demonstrate the feasibility of the organization of a multicenter quality control for interlaboratory comparison. Therefore, the next EQA study in 2016 aims at being extended to all French virology laboratories performing HSV drug resistance analysis. http://dx.doi.org/10.1016/j.jcv.2015.07.255