Treatment failure in herpes simplex virus type 1 keratitis

Herpes simplex virus type 1 (HSV-1), one of the human herpesviruses, is a frequent cause of recurrent ocular infections. Treatment primarily relies on nucleoside analogues, such as aciclovir (ACV), with or without topical corticosteroids. Treatment failure may be attributed to non-adherence to therapy or inadequate topical corticosteroid dosing, and to a lesser extent to an incorrect diagnosis, coinfection with non-viral pathogens or therapy resistance. ACV resistance (ACV^R) is relatively rare compared with other reasons for treatment failure, but has been documented in 6% of immunocompetent patients with HSV-1 keratitis. ACV^R limits the prophylactic and therapeutic efficacy of nucleoside analogues, potentially leading to clinically refractory disease. In this review, we will address the normal pathogenesis of HSV-1 keratitis, the definition and causes of treatment failure in HSV-1 keratitis, a work-up algorithm to be used in the event of treatment failure, the effect of current treatment regimens on the development of ACV^R keratitis and treatment options for ACV^R keratitis.