Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis

J Infect Dis. 2013 Nov 1;208(9):1359-65. doi: 10.1093/infdis/jit350. Epub 2013 Jul 30.


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.

Keywords: acyclovir prophylaxis; acyclovir resistance; patients; recurrent keratitis; refractory disease; retrospective study; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antiviral Agents
  • Acyclovir