The four most commonly used medications for treatment of cytomegalovirus (CMV) infections are ganciclovir, valganciclovir, foscarnet and cidofovir. Letirmovir is approved for prophylactic therapy in hematopoietic stem cell transplantation.
Ganciclovir targets both the UL97 (phospotransferase) and UL54 (DNA polymerase) genes of CMV, while cidofovir and foscarnet target only UL54. Letermovir, targets subunit 2 of the viral terminase complex (UL56).
During treatment of CMV infections with one of these medications, patients may become resistant and no longer respond to therapy. Mutations in thel UL97 phosphotransferase gene and UL54 polymerase gene lead to resistance to these antiviral drugs. Mutations within UL56 have been shown to confer resistance to Letermovir.
Drug resistance should be suspected when CMV viral loads either persist or increase. Resistance if detected by a combination of PCR to amplify these genes followed by genotypic sequencing. Sequencing detects mutations in UL54, UL56, and UL97 genes.
Results are reported as Resistant or None Detected. CMV resistance testing is available at Eurofins-viracor.
Specimen requirement is a lavender top (EDTA) tube of whole blood.
References
Hakki M, Chou S. The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis. 2011 Dec;24(6):605-11.
Lurain NS and Chou S, Antiviral Drug Resistance of Human Cytomegalovirus, Clin Microbiol Rev 23:.https://doi.org/10.1128/cmr.00009-10
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