Hello Iara Zanella Guterres

In herpes viruses, introduction of single base mutation into the thymidine kinase (TK) and/or DNA polymerase (DNA Pol) genes during low level of replication error associated with DNA synthesis, results in drug resistance in the viruses. This naturally occurring mutation is thought to be a major cause of drug-resistant viruses with some variations in frequencies observed between HSV-1 and HSV-2 and their associated strains.

It is likely that acyclovir resistant (ACVr) mutant induction can occur during prolonged ACV therapy. You may want to refer to the article attached below for more information.

https://www.researchgate.net/publication/7455872_Differential_Mutation_Patterns_in_Thymidine_Kinase_and_DNA_Polymerase_Genes_of_Herpes_Simplex_Virus_Type_1_Clones_Passaged_in_the_Presence_of_Acyclovir_or_Penciclovir

Best.