Epstein-Barr virus replication in oral hairy leukoplakia: response, persistence, and resistance to treatment with valacyclovir

J Infect Dis. 2003 Sep 15;188(6):883-90. doi: 10.1086/378072. Epub 2003 Sep 3.


Nineteen cases of human immunodeficiency virus (HIV)-associated oral hairy leukoplakia (HLP) and Epstein-Barr virus (EBV) replication were treated with high-dose oral valacyclovir to inhibit productive EBV replication. The clinical, histopathological, and molecular viral responses to treatment were assessed in surgical biopsy specimens obtained before, during, and after treatment. In the majority of treated cases, HLP was resolved, and EBV replication was terminated. In many cases, the initial response to inhibition of replication was a persistent, nonproductive, EBV infection of the oral mucosa, characterized by limited expression of replicative EBV genes, especially BZLF1. In some cases, productive EBV replication recurred after discontinuation of treatment with valacyclovir. In a few treated cases, treatment failed, and productive EBV replication persisted, possibly because of the evolution of acyclovir-resistant EBV. In summary, safe treatment of HLP and of EBV replication, with valacyclovir, provides new insight into the mechanisms of EBV persistence in oral mucosa.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyclovir / administration & dosage
  • Acyclovir / analogs & derivatives*
  • Acyclovir / therapeutic use*
  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Drug Resistance, Viral*
  • HIV Infections / complications
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / physiology
  • Humans
  • Leukoplakia, Hairy / drug therapy*
  • Leukoplakia, Hairy / virology
  • Middle Aged
  • Mouth Mucosa / virology
  • Treatment Outcome
  • Valacyclovir
  • Valine / administration & dosage
  • Valine / analogs & derivatives*
  • Valine / therapeutic use*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Viral Proteins
  • Valine
  • Valacyclovir
  • Acyclovir