Substitute CMV therapy in the presence of UL97 mutation – pro
Mutations in the human CMV UL97 kinase gene are a major mechanism of viral resistance to two anti-CMV drugs, ganciclovir (GCV) and maribavir (MBV). GCV, the most widely used and established therapy for CMV, is a substrate for the UL97 kinase. Well-characterised GCV-resistance mutations at UL97 codons 460, 520 and 590-607 impair the phosphorylation of GCV that is necessary for its antiviral activity, presumably by altering substrate recognition.
Prolonged therapy with ganciclovir (GCV) can result in the development of GCV-resistant strains due to mutations in the viral phosphotransferase (UL97 gene) and/or in the viral DNA polymerase (UL54 gene). Case reports suggest that switching to a different drug can reduce viral burdens.
Foscavir is one option and is accepted by the plan. Letermovir is a novel agent that was approved for primary prophylaxis in CMV-seropositive adult allogeneic hematopoietic cell transplant recipients. Since its ability to prevent CMV infections is nto at question, off-label use in this compelx situation appears reasonable and it should be approved as medically necessary.
KatharinaGöhring et al, Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected. SCT Patients.
Computational and Structural Biotechnology Journal Volume 13, 2015, Pages 153-158
Chou S, Bowlin TL. Cytomegalovirus UL97 mutations affecting cyclopropavir and ganciclovir susceptibility. Antimicrob Agents Chemother. 2011;55(1):382-384. doi:10.1128/AAC.01259-10
Foscavir Prescribing Information 2021
Shigle TL, Handy VW, Chemaly RF. Letermovir and its role in the prevention of cytomegalovirus infection in seropositive patients receiving an allogeneic hematopoietic cell transplant. Ther Adv Hematol. 2020;11:2040620720937150. Published 2020 Jun 24. doi:10.1177/2040620720937150