TY - JOUR
T1 - Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis
AU - van Velzen, Monique
AU - van de Vijver, David A M C
AU - van Loenen, Freek B
AU - Osterhaus, Albert D M E
AU - Remeijer, Lies
AU - Verjans, Georges M G M
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
KW - Acyclovir/pharmacology
KW - Aged
KW - Animals
KW - Antiviral Agents/pharmacology
KW - Chemoprevention
KW - Chlorocebus aethiops
KW - Drug Resistance, Viral/drug effects
KW - Female
KW - Herpes Simplex/epidemiology
KW - Herpesvirus 1, Human/drug effects
KW - Humans
KW - Keratitis, Herpetic/epidemiology
KW - Male
KW - Microbial Sensitivity Tests
KW - Middle Aged
KW - Prevalence
KW - Risk Factors
KW - Vero Cells
U2 - 10.1093/infdis/jit350
DO - 10.1093/infdis/jit350
M3 - Article
C2 - 23901090
SN - 0022-1899
VL - 208
SP - 1359
EP - 1365
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 9
ER -