Pritelivir for the treatment of nucleoside analogue–resistant orolabial herpes simplex virus 2 in a person living with HIV

Abstract

Background: Nucleoside analogue–resistant herpes simplex virus infections are increasingly observed especially in immunocompromised patients. Currently, other options for treatment such as foscarnet and cidofovir are limited by difficulty of administration and significant risk of toxicity. Our report describes use of pritelivir, a novel helicase-primase inhibitor, in the treatment of nucleoside analogue–refractory orolabial HSV-2 infection. Methods: In 2017, a 53-year-old male with HIV on therapy presented with swelling of the right upper lip and a solid lesion inferior to the right nostril. Biopsy revealed cytopathic effects and immunohistochemistry staining confirming herpes simplex virus infection. The patient received multiple treatment courses including nucleoside analogue therapy, topical and intravenous foscarnet and cidofovir, and topical imiquimod but these failed to establish a significant and durable therapeutic response. Results: A swab of the lesion tested positive for HSV-2 via PCR. Subsequent genotyping revealed a M183X mutation in UL23 expected to convey resistance to acyclovir and penciclovir. The patient was started on oral pritelivir 400 mg once followed by 100 mg daily for 27 days, obtained through Health Canada's Special Access Program, resulting in near complete resolution of the lesion. Conclusion: Pritelivir is a novel helicase-primase inhibitor that appears to be an attractive option for management of resistant herpes simplex infections due to its unique mechanism, excellent oral bioavailability, and minimal toxicity. To our knowledge, this is the first described case of treatment of nucleoside analogue–resistant orolabial herpes simplex 2 infection with pritelivir and the first documented use of pritelivir in Canada.