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Войти в исследования Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 1999
Ganciclovir resistance and UL97 gene mutations in cytomegalovirus blood isolates from patients with AIDS treated with ganciclovir.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Abraham B, Lastere S, Reynes J, Bibollet-Ruche F, Vidal N, Segondy M
Аннотация
BACKGROUND: Treatment of cytomegalovirus (CMV) diseases with protracted administration of ganciclovir can promote the development of resistant CMV that 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 patients with AIDS treated with ganciclovir and to identify the UL97 gene mutations associated with ganciclovir resistance.
STUDY DESIGN: Analysis of CMV blood isolates obtained over 1 year from patients treated with ganciclovir. CMV susceptibility to ganciclovir was determined by an immediate early antigen plaque reduction assay; UL97 gene mutations 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 duration of 5.5 months, were resistant to ganciclovir. Five of the seven patients 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 developed a ganciclovir-resistant virus after a ganciclovir treatment shorter than 60 days (28-58 days). In another patient, we observed that ganciclovir resistance persisted 4 months after discontinuation of ganciclovir therapy.
CONCLUSION: Our results indicate that ganciclovir resistance due to UL97 gene mutations is common in subjects with AIDS-related CMV diseases treated with ganciclovir. Detection of these mutations represents a tool for the management of patients with ganciclovir therapy.
OBJECTIVES: To evaluate the frequency of CMV resistance to ganciclovir in patients with AIDS treated with ganciclovir and to identify the UL97 gene mutations associated with ganciclovir resistance.
STUDY DESIGN: Analysis of CMV blood isolates obtained over 1 year from patients treated with ganciclovir. CMV susceptibility to ganciclovir was determined by an immediate early antigen plaque reduction assay; UL97 gene mutations 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 duration of 5.5 months, were resistant to ganciclovir. Five of the seven patients 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 developed a ganciclovir-resistant virus after a ganciclovir treatment shorter than 60 days (28-58 days). In another patient, we observed that ganciclovir resistance persisted 4 months after discontinuation of ganciclovir therapy.
CONCLUSION: Our results indicate that ganciclovir resistance due to UL97 gene mutations is common in subjects with AIDS-related CMV diseases treated with ganciclovir. Detection of these mutations represents a tool for the management of patients with ganciclovir therapy.