Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis

Monique van Velzen, David A M C van de Vijver, Freek B van Loenen, Albert D M E Osterhaus, Lies Remeijer, Georges M G M Verjans

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK).

METHODS: Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK.

RESULTS: Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89).

CONCLUSIONS: The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

Original languageEnglish
Pages (from-to)1359-65
Number of pages7
JournalThe Journal of infectious diseases
Issue number9
Publication statusPublished - 1 Nov 2013


  • Acyclovir/pharmacology
  • Aged
  • Animals
  • Antiviral Agents/pharmacology
  • Chemoprevention
  • Chlorocebus aethiops
  • Drug Resistance, Viral/drug effects
  • Female
  • Herpes Simplex/epidemiology
  • Herpesvirus 1, Human/drug effects
  • Humans
  • Keratitis, Herpetic/epidemiology
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Prevalence
  • Risk Factors
  • Vero Cells


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