Pathophysiology and treatment of acyclovir-resistant herpes simplex virus keratitis

Herpetic keratitis (HK) caused by herpes simplex virus 1 (HSV-1) is the major cause of infection-related blindness in developed countries. Current treatment is based on curative and preventive use of antiherpetic acyclic nucleoside analogues (ANAs), namely acyclovir (ACV) or other molecules with the same mechanism of action. The frequency of HK caused by acyclovir-resistant viruses is steadily increasing. Virological proof of resistance is obtained from an ocular sample sent to a specialized laboratory. Genotypic characterization by DNA sequencing of the viral enzymes targeted by antivirals allows adaptation of treatment according to the mutation identified. Mutations of the viral thymidine kinase (TK) are the most frequent and leave few viable alternatives for long-term prophylactic treatment among currently available drugs. Amenamevir (AMNV), a new drug targeting the viral helicase-primase (HP) enzyme complex, with proven efficacy for treatment of herpetic infections of other sites, has recently shown value in the management of ACV-resistant HK. Its TK-independent mechanism allows it to retain its antiviral activity even in cases of patient resistance to ACV.