Susceptibility to acyclovir of herpes simplex virus isolates obtained between 1977 and 1996 in Japan

The susceptibility of genital herpes to acyclovir (ACV) in immunocompetent women was examined, as was the frequency of ACV-resistant viruses by analyz ing 56 clinical isolates in Japan between 1977 and 1996. The mean susceptib ilities of herpes simplex virus (HSV) type 1 and type 2 were 0.13 +/- 0.74 and 0.42 +/- 0.14 mug/ml, respectively, assessed by the 50% inhibitory conc entration of plaque formation. The susceptibility to ACV of clinical isolat es did not changed since 1977, and also that of nine pairs of HSV-1 and HSV -2 isolates was not affected by ACV treatment. In order to characterize the change in the virus population, the quantitation of the ACV-resistant viru s in 10(4) plaque forming units (PFU) of clinical isolates was adopted. The mean frequencies of ACV-resistant viruses per 10(4) PFU for all strains of HSV-1 and HSV-2 were 0.31 +/- 0.41 and 9.74 +/- 14.83, respectively, and w ere not influenced by ACV treatment. Additionally, the phenotypes of ACV-re sistance were not influenced by ACV treatment, and more than 90% of ACV-res istant viruses were found to be thymidine kinase-deficient. This study char acterized clinical isolates with respect to ACV susceptibility as a populat ion and the quantitative and qualitative characterization of ACV-resistant virus in the virus population of clinical isolates was also studied. The su sceptibility of isolates from genital lesions, the frequency of ACV-resista nt viruses, and also the phenotypic characterization of ACV-resistant virus es was maintained between 1977 and 1996, even after the introduction of ACV treatment for genital herpes in Japan. (C) 2001 Wiley-Liss, Inc.