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| |  UL97 Genotyping Can Detect Transplant Recipients Resistant to Ganciclovir: Presented at ICC By Louise Gagnon TORONTO -- June 23, 2009 -- Researchers have developed a method to quickly detect for ganciclovir resistance in patients who have undergone a solid organ transplant, providing evidence for physicians to make an adjustment to therapy in transplant recipients, according to researchers here at the 26th International Congress of Chemotherapy and Infection (ICC). The study analysed 650 specimens from patients who had suspected failure of ganciclovir therapy because of the development of mutations that confer resistance to the therapy. Resistance to ganciclovir develops because of mutations in the UL97 protein, explained Detlef Michel, PhD, Virus Diagnostic Lab, Institute of Virology, University Hospital, Ulm, Germany, on June 19. "Clinicians don't test for this, and resistance can develop," Dr. Michel said in an interview. "Clinicians may make a therapeutic decision like increasing the dose when they see there is a loss of activity. That decision is based on a gut feeling and not based on evidence." Because titrating the dose of ganciclovir is not a step that makes therapeutic progress in patients whose human cytomegalovirus DNA is resistant to the antiviral medication, patients worsen and end up going to the intensive care unit in many instances, according to Dr. Michel. A total of 485 specimens allowed amplification of the UL97 region via polymerase chain reaction (PCR). The analysis revealed that 360 specimens carried wild-type UL97 and 135 carried at least 1 mutation, including 4 deletions, that trigger resistance to ganciclovir. In 49 specimens with genotypic resistance, mixed virus populations could be detected. Eighty of the PCR specimens that were positive for HCMV could be isolated for subsequent phenotyping. Investigators detected a sensitive UL97 genotype from isolated viruses coming from specimens containing UL97 sequences with mutations that confer resistance to ganciclovir. Results of the assay can be available in several hours, said Dr. Michel, stressing that transplantation centres should have access to this genotypic analysis of UL97. [Presentation title: Fast Detection of Ganciclovir-Resistant Human Cytomegalovirus by UL97 Genotyping for Therapy Monitoring in Solid Organ Transplant Patients. Abstract 019]
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