Added-value of high-throughput sequencing for early detection of HSV-2 resistant subpopulations in the helicase-primase inhibitors era: A case report.

Immunocompromised patients are at high risk of developing acyclovir-resistant (ACV) herpes simplex virus (HSV) infections. Helicase-primase inhibitors, including pritelivir (PTV), represent an antiviral option to nephrotoxic alternatives. This report describes the course of an immunocompromised patient infected with HSV-2 treated with PTV and highlights the importance of high throughput sequencing (HTS) for resistance emergence monitoring. After 7 months of ACV treatment, resistance was detected and associated with the emergence of minority subpopulations. Several PTV courses were then administered, which were associated with clinical improvement. HTS technologies enhance sensitivity over conventional methods and provide valuable insights for managing antiviral resistance. Continuous monitoring and research to elucidate the functional impact of specific mutations of unknown significance on drug resistance are essential for building robust HSV resistance databases.