In vitro sensitivity to acyclovir in genital herpes simplex viruses from acyclovir-treated patients

Genital isolates of herpes simplex virus (HSV) from patients given acyclovir or placebo were tested in vitro for sensitivity to acyclovir. Isolates obtained before therapy were sensitive to acyclovir concentrations of 0.01-19 micrograms/ml, with 86 of 97 isolates inhibited by less than 1 microgram/ml. Before therapy, six patients had isolates of HSV type 2 with ID50 values (concentrations of drug reducing viral cytopathic effect by 50%) of greater than 3 micrograms/ml. Plaque purification revealed mixed populations of virus; some clones were associated with high and some with low rates of acyclovir phosphorylation. Sensitivity to acyclovir decreased in isolates obtained after therapy from four of 25 patients given acyclovir and three of 30 patients given placebo. The occurrence of this change with similar frequency in the two groups suggests that factors other than the use of acyclovir influence the in vitro sensitivity of clinical HSV isolates to this agent. In one patient in whom an acyclovir-resistant, thymidine kinase-negative strain of HSV type 2 emerged during therapy, infection subsequently recurred. The isolate responsible for the recurrence was sensitive to acyclovir and had a high level of acyclovir-phosphorylating activity.