Title
Evaluation of Genotypic Antiviral Resistance Testing as an Alternative to Phenotypic Testing in a Patient with DOCK8 Deficiency and Severe HSV-1 Disease
Document Type
Article
Publication Date
6-11-2020
Identifier
DOI: 10.1093/infdis/jiaa020; PMCID: PMC7289554 (available on 2021-06-11)
Abstract
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. Antiviral resistance frequently complicates the treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we present the case of an adolescent boy with dedicator of cytokinesis 8 (DOCK8) deficiency, who experienced recurrent infections with resistant HSV-1. We used both phenotypic and genotypic methodologies to characterize the resistance profile of HSV-1 in the patient and conclude that genotypic testing outperformed phenotypic testing. We also present the first analysis of intrahost HSV-1 evolution in an immunocompromised patient. While HSV-1 can remain static in an immunocompetent individual for decades, the virus from this patient rapidly acquired genetic changes throughout its genome. Finally, we document a likely case of transmitted resistance in HSV-1 between the patient and his brother, who also has DOCK8 deficiency. This event demonstrates that resistant HSV-1 is transmissible among immunocompromised persons.
Journal Title
The Journal of infectious diseases
Volume
221
Issue
12
First Page
2035
Last Page
2042
Keywords
DOCK8 deficiency, genotypic antiviral resistance, HSV-1, immunodeficiency, intrahost evolution, phenotypic antiviral resistance, transmitted resistance
Recommended Citation
Casto, A. M., Stout, S. C., Selvarangan, R., Freeman, A. F., Newell, B. D., Stahl, E., Ahmed, A. A., Greninger, A. L., Yin, D. E. Evaluation of Genotypic Antiviral Resistance Testing as an Alternative to Phenotypic Testing in a Patient with DOCK8 Deficiency and Severe HSV-1 Disease The Journal of infectious diseases 221, 2035-2042 (2020).
Comments
Grant support