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.
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.
Authors: John E Tavis; Hong Wang; Ann E Tollefson; Baoling Ying; Maria Korom; Xiaohong Cheng; Feng Cao; Katie L Davis; William S M Wold; Lynda A Morrison Journal: Antimicrob Agents Chemother Date: 2014-09-29 Impact factor: 5.191
Authors: Peter J Ireland; John E Tavis; Michael P D'Erasmo; Danielle R Hirsch; Ryan P Murelli; Mark M Cadiz; Bindi S Patel; Ankit K Gupta; Tiffany C Edwards; Maria Korom; Eileen A Moran; Lynda A Morrison Journal: Antimicrob Agents Chemother Date: 2016-03-25 Impact factor: 5.191
Authors: James M Hill; Debra C Quenelle; Rhonda D Cardin; Jodi L Vogel; Christian Clement; Fernando J Bravo; Timothy P Foster; Marta Bosch-Marce; Priya Raja; Jennifer S Lee; David I Bernstein; Philip R Krause; David M Knipe; Thomas M Kristie Journal: Sci Transl Med Date: 2014-12-03 Impact factor: 17.956
Authors: Natacha Coen; Sophie Duraffour; Kazuhiro Haraguchi; Jan Balzarini; Joost J van den Oord; Robert Snoeck; Graciela Andrei Journal: Antimicrob Agents Chemother Date: 2014-05-12 Impact factor: 5.191
Authors: Takashi Masaoka; Haiyan Zhao; Danielle R Hirsch; Michael P D'Erasmo; Christine Meck; Brittany Varnado; Ankit Gupta; Marvin J Meyers; Joel Baines; John A Beutler; Ryan P Murelli; Liang Tang; Stuart F J Le Grice Journal: Biochemistry Date: 2016-02-01 Impact factor: 3.162