Lack of selection by acyclovir (ACV) therapy of highly ACV-resistant HSV2 clones detected before therapy in a patient with severe genital lesions

Summary Sequential isolates of herpes simplex virus type 2 (HSV2) from an immunocompetent woman with severe genital herpes infection were examined for their sensitivity to acyclovir. The inhibitory concentration 50% (IC50) values of the HSV2 isolates obtained before, during and after ACV therapy did not show any significant variation. Meanwhile, the direct sampling examination of clinical specimens by a chessboard titration technique revealed three important points: 1) The presence of viruses highly resistant to up to 100 μM of ACV in the pretreatment clinical specimen; 2) The lack of prevalence of these resistant components under ACV therapy; 3) The emergence of a small proportion of 10 μM ACV-resistant viruses in the late recurrence. One of the highly resistant mutants picked up under 100 μM ACV had a 110 μM IC50 value. This mutant exhibited a marked decrease of thymidine kinase activity in vitro and remained sensitive to PAA, an inhibitor of viral DNA polymerase.