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

J Infect Dis. 2021 Sep 17;224(6):1024-1028. doi: 10.1093/infdis/jiab029.

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.

Keywords: CMV; antiviral drug resistance; cytomegalovirus; ganciclovir; maribavir; transplantation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use*
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections / drug therapy*
  • Drug Resistance, Viral / drug effects
  • Drug Resistance, Viral / genetics*
  • Female
  • Ganciclovir / pharmacology
  • Ganciclovir / therapeutic use*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cells
  • Humans
  • Kidney Transplantation / adverse effects*
  • Mutation / drug effects
  • Organ Transplantation
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / therapeutic use
  • Ribonucleosides / pharmacology
  • Ribonucleosides / therapeutic use*
  • Transplant Recipients*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Ribonucleosides
  • Phosphotransferases (Alcohol Group Acceptor)
  • Ganciclovir
  • maribavir