Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France

Antiviral Res. 2014 Nov:111:36-41. doi: 10.1016/j.antiviral.2014.08.013. Epub 2014 Sep 8.

Abstract

The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance.

Keywords: Antiviral drug resistance; Hematopoietic stem cell transplant patients; Herpes simplex virus; Survey; UL23 thymidine kinase; UL30 DNA polymerase.

MeSH terms

  • Acyclovir / therapeutic use*
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Resistance, Viral*
  • Female
  • France / epidemiology
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / epidemiology
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / metabolism
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / metabolism
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation
  • Retrospective Studies
  • Viral Proteins / genetics
  • Young Adult

Substances

  • Antiviral Agents
  • Viral Proteins
  • Acyclovir