Evaluation of Genotypic Antiviral Resistance Testing as an Alternative to Phenotypic Testing in a Patient with DOCK8 Deficiency and Severe HSV-1 Disease

J Infect Dis. 2020 Jun 11;221(12):2035-2042. doi: 10.1093/infdis/jiaa020.


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.

Keywords: DOCK8 deficiency; HSV-1; genotypic antiviral resistance; immunodeficiency; intrahost evolution; phenotypic antiviral resistance; transmitted resistance.

Publication types

  • Case Reports
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Drug Resistance, Viral / genetics*
  • Genotyping Techniques / methods*
  • Guanine Nucleotide Exchange Factors / deficiency*
  • Guanine Nucleotide Exchange Factors / immunology
  • Herpes Simplex / diagnosis
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / immunology
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / isolation & purification
  • Humans
  • Immunocompromised Host / genetics
  • Male
  • Microbial Sensitivity Tests / methods
  • Polymorphism, Single Nucleotide
  • Severity of Illness Index
  • Skin / pathology
  • Skin / virology


  • Antiviral Agents
  • DNA, Viral
  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors