4.7 Article

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 224, Issue 6, Pages 1024-1028

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab029

Keywords

cytomegalovirus; CMV; antiviral drug resistance; maribavir; ganciclovir; transplantation

Funding

  1. Fondo de Investigacion en Salud (FIS) of the Instituto de Salud Carlos III [PI 17/0150]
  2. Ministerio de Ciencia e Inovacion del Gobierno de Espana
  3. Ministerio de Economia y Competitividad
  4. Agency for Health Technology Assessment

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For transplant recipients with CMV infection resistant to standard therapy, MBV could be an effective treatment option. However, the emergence of MBV resistance should be carefully monitored through clinical follow-up and genotypic and phenotypic studies.
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.

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