Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients

Abstract Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurr...

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Bibliographic Details
Published in:The Journal of infectious diseases 2021-09, Vol.224 (6), p.1024-1028
Main Authors: Santos Bravo, Marta, Plault, Nicolas, Sánchez Palomino, Sonsoles, Mosquera Gutierrez, María Mar, Fernández Avilés, Francesc, Suarez Lledo, María, Sabé Fernández, Nuria, Rovira, Montserrat, Alain, Sophie, Marcos Maeso, M Ángeles
Format: Article
Language:English
Subjects:
Adult
Antiviral Agents - pharmacology
Antiviral Agents - therapeutic use
Antiviral drugs
Benzimidazoles - pharmacology
Benzimidazoles - therapeutic use
Cross-resistance
Cytomegalovirus
Cytomegalovirus - drug effects
Cytomegalovirus - genetics
Cytomegalovirus Infections - drug therapy
Drug Resistance, Viral - drug effects
Drug Resistance, Viral - genetics
Female
Ganciclovir
Ganciclovir - pharmacology
Ganciclovir - therapeutic use
Genotypes
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cells
Humans
Kidney Transplantation - adverse effects
Kidney transplants
Mutation - drug effects
Organ Transplantation
Patients
Phenotypes
Phenotyping
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - therapeutic use
Recurrent infection
Ribonucleosides - pharmacology
Ribonucleosides - therapeutic use
Stem cell transplantation
Stem cells
Transplant Recipients
Treatment Outcome
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Summary:Abstract Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance. A cytomegalovirus UL97 C480F mutation emerged after maribavir treatment in 2 transplant recipients (1 kidney, 1 hematopoietic stem cell). Phenotypic assay confirmed that C480F confers a high level of maribavir resistance and ganciclovir cross-resistance, with a decreased replicative capacity.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiab029