PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF ACYCLOVIR-RESISTANT VARICELLA-ZOSTER VIRUSES ISOLATED FROM PERSONS WITH AIDS

Phenotypic and genotypic analyses were done on 17 varicella-zoster vir us (VZV) isolates recovered from 10 persons with AIDS (mean CD4 cell c ount, 16.4/mm(3)) who had chronic VZV lesions. Eleven acyclovir-resist ant isolates were recovered from 10 patients after a mean of 20.1 week s of therapy. Six susceptible isolates were recovered before acyclovir treatment (n = 1), early during therapy (n = 4; mean time, 4.2 weeks) , or after discontinuation of acyclovir (n = 1). Acyclovir-resistant V ZV isolates were deficient in thymidine kinase (TK) or induced a TK wi th altered substrate specificity; all isolates were susceptible to fos carnet. Ten of 11 acyclovir-resistant mutants contained tk gene mutati ons, including single nucleotide substitutions in highly conserved bin ding sites (n = 2) as well as nucleotide deletions (n = 4) and inserti ons (n = 4). These findings suggest that multiple, nonuniform mutation s within the Ik gene are associated with acyclovir-resistant VZV pheno types.