Cytomegalovirus (CMV) infections are a major cause of disease among immunocompromised patients. In this population, prolonged antiviral therapy is often necessary to prevent or treat CMV disease, which may lead to development of antiviral resistance (AVR). Timely identification of viral mutations conferring resistance is essential for effective patient management. Nucleotide sequencing provides assessment of mutations in the CMV UL97 and UL54 genes that are known to confer resistance to ganciclovir, cidofovir, and foscarnet. This assay uses polymerase chain reaction (PCR) of the UL97and UL54 sequences followed by Sanger sequencing. Sequences were analyzed with ABIs Variant Reporter v1.0 software. The optimal minimal viral load (VL) for AVR mutation analysis is 1,000 copies/mL, although results were obtained at considerably lower VL values. To assess assay performance, results from a randomly selected period of time were reviewed. In this set of 501 plasma samples, 331 samples (66.1%) were observed to have no mutations known to confer AVR. Of the remaining 170 samples (33.9%) with at one least known AVR mutation, 105 samples had UL97 mutations only, and 28 samples had UL54 mutations only. A total of 37 samples had AVR mutations in both UL97 and UL54 genes. For the 142 samples with at least one UL97 mutation, 20 samples had at least one additional AVR mutation in the same gene. For the 65 of samples with at least one UL54 mutation, 11 had additional AVR mutations in this gene. Samples with no known AVR mutations had a mean (±SD) VL of 3.95 ± 1.03 log10 copies/mL, while samples with one or more mutation in UL97 had a mean (±SD) VL of 4.03 ± 1.08 log10 copies/mL, and samples with one or more mutation in UL54 had a mean (±SD) VL of 3.69 ± 0.76 log10 copies/mL. Samples with mutations in both UL54 and UL97 had a mean (±SD) VL of 3.88 ± 0.81 log10 copies/mL. Regarding elapsed time from sample receipt to release of results to the physician, 9.2% of results were reported within 48 hrs, 43.5% from 48 72 hrs, 33.9% from 72 96 hrs, and 13.4% after 96 hrs. In summary, review of 501 results demonstrated that viral genomic mutations known to confer AVR were common; however, the CMV VL did not differ between samples with or without the presence of AVR mutations. A majority of results were reported within 4 days of sample receipt, allowing physicians to make treatment decisions based on objective data.
Kleiboeker, S.: Employee, Viracor-IBT Laboratories. Schindel, B.: Employee, Viracor-IBT Laboratories. Altrich, M.: Employee, Viracor-IBT Laboratories. Hester, J.: Employee, Viracor-IBT Laboratories. Dannehl, J.: Employee, Viracor-IBT Laboratories. Caton, I.: Employee, Viracor-IBT Laboratories. Nutt, J.: Employee, Viracor-IBT Laboratories.
To cite this abstract in AMA style:Kleiboeker S, Schindel B, Altrich M, Hester J, Dannehl J, Caton I, Nutt J. Assessment of CMV Antiviral Resistance Mutations in Clinical Samples [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/assessment-of-cmv-antiviral-resistance-mutations-in-clinical-samples/. Accessed October 27, 2020.
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