Antiviral drug resistance in cytomegalovirus complicating hematopoietic stem cell transplantation: prevalence, genotypic analysis and novel <i>UL97/UL54</i> variants

This study investigated antiviral resistance by sequencing <i>UL97</i> and <i>UL54</i> in cytomegalovirus (CMV) strains from haematology and hematopoietic stem cell transplant (HSCT) patients. Fifty-one samples from 48 patients (21 paediatric and 27 adult) with CMV DNA ≥1000 IU/mL and persistent viremia despite therapy were analysed. Resistance-associated mutations were identified in 6/48 patients (12.5%), all HSCT recipients - three paediatric and three adults. Detected mutations included <i>UL97</i> (A591V, E596G and C603W), combined <i>UL97</i> (M460I and C592G) and <i>UL54</i> (F412L) mutations, and a <i>UL54</i> (L957F) mutation. Additionally, 28 patients harboured 11 previously reported variants not associated with resistance. Novel <i>UL97</i> (<i>n</i> = 18) and <i>UL54</i> (<i>n</i> = 20) variants were also identified. In conclusion, prevalence of CMV antiviral resistance was 14.2% in CMV-infected HSCT recipients, slightly higher in paediatric patients. Detection of known and novel <i>UL97</i>/<i>UL54</i> mutations highlights the importance of monitoring and the need for studies to assess the clinical impact of novel variants.