Phenotype and genotype study of novel C480F maribavir-ganciclovir cross-resistance mutation detected in hematopoietic stem cell and solid organ transplanted patients.

Two kidney and hematopoietic stem-cell transplant recipients 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 cumulative 2 months of MBV and 15 or 4 weeks of valganciclovir/gangciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up, genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.