Overview on the management of herpes simplex virus infections: Current therapies and future directions

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent, infecting approximately 64 % and 13 % of the world's population, respectively. Traditionally, HSV-1 has been associated with orofacial infections and HSV-2 with anogenital infections, but HSV-1 is increasingly the cause of genital infections. The clinical spectrum of HSV disease ranges from mild cold sores to severe conditions such as encephalitis or systemic infection, particularly in immunocompromised individuals and neonates.

Here we summarize the natural history, epidemiology, manifestations, and treatment options for HSV infections. Current treatments, such as acyclovir, target viral DNA polymerase but have limited efficacy and are susceptible to resistance, especially in immunosuppressed populations. Rescue therapies such as foscarnet exhibit limiting toxicity. Vaccine development has been challenging, and a cure for HSV infection remains distant. Gene therapy is still in its early stages, while novel drugs such as helicase primase inhibitors (HPIs) are emerging as a promising alternative, showing high efficacy and the potential to overcome resistance.

HPIs represent a significant advance in HSV management. Their safety profile and novel mode of action may provide better viral suppression with a lower risk of resistance, offering hope for better control of the disease.