Acyclovir-resistant HSV-1 keratitis: a concerning and emerging clinical challenge

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Rousseau, Antoine | Burrel, Sonia | Gueudry, Julie | Deback, Claire | Haigh, Oscar | Schweitzer, Cedric | Boutolleau, David | Labetoulle, Marc

Edité par CCSD ; Elsevier Masson -

International audience. Purpose To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACV(R)) strains of herpes simplex virus 1 (HSV-1). Design Multicenter retrospective case series. Methods HSV-1 resistance to ACV was confirmed using sequencing of genes encoding HSV-1 thymidine kinase (TK) and DNA polymerase (DNA pol). Data were collected on the number of HSK episodes before and after the diagnosis of resistance, ocular findings including the type of HSK, immune status of patients, antiviral treatments and HSV-1 genotypic resistance profiles. Results This study evaluated 18 HSK patients (13 males, 5 females, 66.8±4.7 years) with ACV(R) HSV-1 positive ocular samples. Genotypic resistance testing was performed due to frequent recurrences despite adequate antiviral prophylaxis (AVP) (N=13, 72%), or poor response to suppressive antiviral therapy (N=5, 28%). Resistance mutations were found in the TK (N=15, 83%) or in the DNA pol gene (N=3, 17%). Prior to the diagnosis of resistance, duration of disease was 29.8±20.4 years with more than 10 HSK recurrences in 15 patients (83%). The number of recurrences between the first episode and the diagnosis of resistance was significantly lower in immunocompromised patients (N=6, 33%), than in immunocompetent patients (N=12; 67%) (11.5±4.9 versus 16.4±1.9, P=0.05). Conclusion HSV-1 resistance to ACV must be suspected in HSK patients with recurrences despite AVP and/or in cases that respond poorly to a suppressive antiviral regimen. Immunocompromised patients and/or those with a long-standing disease, may be particularly at risk for developing resistance.

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