title: Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Viroscience, Erasmus MC.
authors.forename: Monique
authors.initials: M
authors.lastname: van Velzen
authors.forename: David A M C
authors.initials: DA
authors.lastname: van de Vijver
authors.forename: Freek B
authors.initials: FB
authors.lastname: van Loenen
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Lies
authors.initials: L
authors.lastname: Remeijer
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
mesh_terms: D000212:Acyclovir / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018890:Chemoprevention; D002522:Chlorocebus aethiops; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D006561:Herpes Simplex / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D016849:Keratitis, Herpetic / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir
keywords: acyclovir prophylaxis; acyclovir resistance; patients; recurrent keratitis; refractory disease; retrospective study; risk factors