We have examined the susceptibility to
acyclovir and frequency of
acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive
therapy (200 mg/day) for 1-9 years and 15 patients naive to
acyclovir. Suppressive
therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml
acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of
acyclovir, were subjected to the
acyclovir susceptibility test, and 155 clones isolated in the presence of
acyclovir were analysed for the mechanisms of resistance to
acyclovir. There were no significant differences in the susceptibility to
acyclovir, the frequency of
acyclovir-resistant virus and the ratio of
thymidine kinase-deficient viruses in
acyclovir-resistant viruses between the two groups. The frequency of
acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with
genital herpes with or without
acyclovir-suppressive
therapy. Thus, the low dose of
acyclovir suppressive
therapy did not affect the susceptibility to
acyclovir or increase the frequency of
acyclovir-resistant viruses in the genital lesions.