Study of cytomegalovirus resistance in allogeneic hematopoietic cell transplant recipients

Med Clin (Barc). 2020 Jun 12;154(11):433-439. doi: 10.1016/j.medcli.2019.07.027. Epub 2019 Nov 27.
[Article in English, Spanish]

Abstract

Introduction: Cytomegalovirus (CMV) is the most important opportunistic pathogen associated with transplant. The objective of this study was the characterization of CMV resistance mutations in allogeneic haematopoietic cell transplant recipients (allo-TPH) and the study of associated factors.

Methods: A retrospective study of a cohort of allo-TPH recipients with post-transplant CMV reactivations with stable or increasing viral loads (CV), despite adequate antiviral treatment for at least 2weeks. The study of resistance mutations of the UL97 and UL54 genes was carried out by Sanger sequencing.

Results: Refractory CMV infection in our group of allo-TPH patients corresponded with a 21.43% rate of resistant virus infection (3 of 14 patients). All patients with resistance mutations had multiple reactivation episodes (P-value .01). The mutations found were A594V and H520Q in the UL97 gene that confers high-grade resistance to ganciclovir (GCV). One of the 3 cases with antiviral resistance was documented with a low VL (< 1000 copies/ml) and short accumulated GCV treatment (41 days).

Conclusion: Most of the failures in the treatment of CMV were possibly due to clinical resistance; the lack of satisfactory response to antiviral treatment is not always accompanied by virological resistance. However, the appearance of resistances can occur early after the start of the treatment and with VL below 1000 copies / ml. The number of episodes of reactivation was higher among patients with virological resistance than those who did not.

Keywords: Allogeneic haematopoietic cell transplant; Citomegalovirus; Cytomegalovirus; Mutaciones de resistencia; Resistance mutations; Trasplante alogénico de progenitores hematopoyéticos.

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus* / genetics
  • Drug Resistance, Viral / genetics
  • Ganciclovir / therapeutic use
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Mutation
  • Retrospective Studies
  • Transplant Recipients

Substances

  • Antiviral Agents
  • Ganciclovir