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 (ACVR) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK).Methods. Frequencies of ACVR 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 ACVR rHK.Results. Corneal HSV-1 isolates with >28% ACVR viruses were defined as ACVR 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 ACVR isolates. Moreover, a corneal ACVR 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 ACVR HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

acyclovir prophylaxis, acyclovir resistance, patients, recurrent keratitis, refractory disease, retrospective study, risk factors
dx.doi.org/10.1093/infdis/jit350, hdl.handle.net/1765/62404
The Journal of Infectious Diseases
Department of Virology

van Velzen, M, van de Vijver, D.A.M.C, van Loenen, F.B, Osterhaus, A.D.M.E, Remeijer, L, & Verjans, G.M.G.M. (2013). Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis. The Journal of Infectious Diseases, 208(9), 1359–1365. doi:10.1093/infdis/jit350