期刊
JOURNAL OF CLINICAL VIROLOGY
卷 167, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jcv.2023.105554
关键词
Herpes simplex virus; Antiviral resistance; Viral sequencing; Genotypic testing; Acyclovir; Plaque reduction assay
类别
Antiviral resistance in human herpes simplex viruses (HSV) remains a clinical challenge. Current methods for HSV resistance testing rely on viral culture and take weeks for results. This study evaluated the performance of genotypic antiviral resistance testing using whole genome sequencing and found that combining genotypic and phenotypic testing can accurately diagnose HSV resistance and likely provide faster results.
Background: Antiviral resistance in human herpes simplex viruses (HSV) remains a significant clinical challenge in immunocompromised populations. Although molecular tests have largely replaced viral culture for HSV diagnosis and molecular antiviral resistance testing is available for many viruses, HSV resistance testing continues to rely on phenotypic, viral culture-based methods, requiring weeks for results. Consequently, treatment of suspected HSV resistance remains largely empiric.Methods: We used HSV whole genome sequencing and a database of previously characterized HSV acyclovir and foscarnet resistance mutations to evaluate the performance of genotypic antiviral resistance testing among 19 control strains compared to in-house plaque reduction assay (PRA) and 25 clinical isolates sent for reference lab PRA antiviral resistance testing.Results: Among control strains, 23/29 (79.3%) results were concordant, 5 (17.2%) were indeterminate, and 1 (3.4%) was discordant. Indeterminate results were caused by variants of uncertain significance (VUS), including mutations without published phenotypes and mutations with contradictory results. Among clinical isolates, 14/ 40 (35%) results were concordant, 17 (42.5%) were indeterminate, and 9 (22.5%) were discordant. All discordant results were in reportedly phenotypically-susceptible HSV-1 strains yet possessed resistance mutations. Three contained resistant subpopulations. 6/8 (75%) discordant phenotypes were concordant with resistant genotypes upon repeat PRA.Conclusions: These data support the combination of genotypic and phenotypic testing to diagnose HSV resistance more accurately and likely more rapidly than phenotypic testing alone. Genotypic context of resistance mutations and the ability of viral strains to form plaques in culture may affect phenotypic resistance results, highlighting the limitations of PRA alone as a gold standard method.
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