Ganciclovir resistance and UL97 gene mutations in cytomegalovirus blood isolates from patients with AIDS treated with ganciclovir

Background: Treatment of cytomegalovirus (CMV) diseases with protracted adm inistration of ganciclovir can promote the development of resistant CMV tha t is associated with a poor response to therapy. It has been shown that the majority of ganciclovir-resistant CMV isolates carry mutations in the UL97 phosphotransferase gene. Objectives: To evaluate the frequency of CMV resistance to ganciclovir in p atients with AIDS treated with ganciclovir and to identify the UL97 gene mu tations associated with ganciclovir resistance. Study design: Analysis of CMV blood isolates obtained over 1 year from pati ents treated with ganciclovir. CMV susceptibility to ganciclovir was determ ined by an immediate early antigen plaque reduction assay; UL97 gene mutati ons were identified by restriction enzyme digest analysis and sequencing. Results: Twenty-nine patients were followed-up; 17 CMV blood isolates were obtained from 10 ganciclovir-experienced patients. Thirteen (76%) of these isolates, obtained from seven (24%) patients after a median treatment durat ion of 5.5 months, were resistant to ganciclovir. Five of the seven patient s who had a ganciclovir-resistant CMV in blood showed retinitis progression . UL97 gene mutations were identified in nine CMV isolates at codons 460 (M --> V), 594 (A --> V and A --> T), and 595(L --> S). Three patients develo ped a ganciclovir-resistant virus after a ganciclovir treatment shorter tha n 60 days (28-58 days). In another patient, we observed that ganciclovir re sistance persisted 4 months after discontinuation of ganciclovir therapy. Conclusion: Our results indicate that ganciclovir resistance due to UL97 ge ne mutations is common in subjects with AIDS-related CMV diseases treated w ith ganciclovir. Detection of these mutations represents a tool for the man agement of patients with ganciclovir therapy. (C) 1999 Elsevier Science B.V . All rights reserved.