Herpes simplex virus drug-resistance: new mutations and insights

Curr Opin Infect Dis. 2013 Dec;26(6):551-60. doi: 10.1097/QCO.0000000000000015.


Purpose of review: Acyclovir (ACV) is the first-line treatment for the management of herpes simplex virus 1 (HSV-1) and 2 (HSV-2) diseases. Long-term administration of the drug for the treatment of chronic infections in the immunocompromised host can lead to the development of ACV-resistance. This review provides an update of the mutations linked to drug-resistance and issues to be considered in the management of HSV infections refractory to antiviral therapy.

Recent findings: Recent data have shown that HSV drug-resistance should be taken into account not only in immunocompromised individuals but also in immunocompetent persons when HSV infections involve 'immune-privileged sites'. Thus, drug-resistance typing is recommended in cases of ACV unresponsive herpetic keratitis and herpes simplex encephalitis. Several issues regarding HSV drug-resistance were highlighted by recent studies. Phenotypic and genotypic antiviral resistance may vary not only from different compartments but also over time, highlighting the importance of characterizing longitudinal HSV isolates from all sites. Combination therapy should be considered when viruses with distinct phenotype/genotype are identified at one or at distinct body sites.

Summary: Surveillance of HSV drug-resistance is highly recommended in immunocompromised patients and in immunocompetent individuals with infections implicating 'immune-privileged sites' to rationally adapt antiviral treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyclovir / pharmacology
  • Acyclovir / therapeutic use*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Herpes Simplex / diagnosis
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / virology
  • Humans
  • Immunocompetence
  • Immunocompromised Host


  • Antiviral Agents
  • Acyclovir