Emergence of Letermovir-resistant HCMV UL56 mutant during rescue treatment in a liver transplant recipient with ganciclovir-resistant infection HCMV: a case report.
Case report
HCMV
Letermovir
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
23 Sep 2021
23 Sep 2021
Historique:
received:
03
12
2020
accepted:
14
09
2021
entrez:
24
9
2021
pubmed:
25
9
2021
medline:
28
9
2021
Statut:
epublish
Résumé
Human Cytomegalovirus (HCMV) still represents a crucial concern in solid organ transplant recipients (SOTRs) and the use of antiviral therapy are limited by side effects and the selection of viral mutations conferring antiviral drug resistance. Here we reported the case of an HCMV seronegative patient with common variable immunodeficiency (CVID), multiple hepatic adenomatosis, hepatopulmonary syndrome and portal hypertension who received a liver transplant from an HCMV seropositive donor. The patient was treated with Valganciclovir (vGCV) and then IV Ganciclovir (GCV) at 5 week post-transplant for uncontrolled HCMV DNAemia. However, since mutation A594V in UL97 gene conferring resistance to ganciclovir was reported, GCV therapy was interrupted. Due to the high toxicity of Foscarnet (FOS) and Cidofovir (CDV), Letermovir (LMV) monotherapy at the dosage of 480 mg per day was administered, with a gradual viral load reduction. However, a relapse of HCMV DNAemia revealed the presence of mutation C325Y in HCMV UL56 gene conferring resistance to LMV. In conclusion, even if LMV is an effective and favorable safety molecule it might have a lower genetic barrier to resistance. A warning on the use of LMV monotherapy as rescue treatments for HCMV GCV-resistant infections in transplant recipients is warranted.
Sections du résumé
BACKGROUND
BACKGROUND
Human Cytomegalovirus (HCMV) still represents a crucial concern in solid organ transplant recipients (SOTRs) and the use of antiviral therapy are limited by side effects and the selection of viral mutations conferring antiviral drug resistance.
CASE PRESENTATION
METHODS
Here we reported the case of an HCMV seronegative patient with common variable immunodeficiency (CVID), multiple hepatic adenomatosis, hepatopulmonary syndrome and portal hypertension who received a liver transplant from an HCMV seropositive donor. The patient was treated with Valganciclovir (vGCV) and then IV Ganciclovir (GCV) at 5 week post-transplant for uncontrolled HCMV DNAemia. However, since mutation A594V in UL97 gene conferring resistance to ganciclovir was reported, GCV therapy was interrupted. Due to the high toxicity of Foscarnet (FOS) and Cidofovir (CDV), Letermovir (LMV) monotherapy at the dosage of 480 mg per day was administered, with a gradual viral load reduction. However, a relapse of HCMV DNAemia revealed the presence of mutation C325Y in HCMV UL56 gene conferring resistance to LMV.
CONCLUSIONS
CONCLUSIONS
In conclusion, even if LMV is an effective and favorable safety molecule it might have a lower genetic barrier to resistance. A warning on the use of LMV monotherapy as rescue treatments for HCMV GCV-resistant infections in transplant recipients is warranted.
Identifiants
pubmed: 34556034
doi: 10.1186/s12879-021-06694-4
pii: 10.1186/s12879-021-06694-4
pmc: PMC8461837
doi:
Substances chimiques
Acetates
0
Antiviral Agents
0
Quinazolines
0
letermovir
1H09Y5WO1F
Ganciclovir
P9G3CKZ4P5
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
994Subventions
Organisme : Fondazione IRCCS Policlinico San Matteo
ID : 80207
Informations de copyright
© 2021. The Author(s).
Références
Antimicrob Agents Chemother. 2019 Feb 26;63(3):
pubmed: 30642941
J Clin Virol. 2014 Sep;61(1):65-73
pubmed: 24961915
J Virol. 2011 Oct;85(20):10884-93
pubmed: 21752907
Med Mal Infect. 2018 Dec;48(8):495-502
pubmed: 29650261
Curr Opin Infect Dis. 2018 Aug;31(4):286-291
pubmed: 29746444
J Antimicrob Chemother. 2004 Mar;53(3):536-9
pubmed: 14739146
N Engl J Med. 2014 May 8;370(19):1781-9
pubmed: 24806159
Antimicrob Agents Chemother. 2014;58(1):128-35
pubmed: 24145525
Curr Opin Pharmacol. 2008 Oct;8(5):541-8
pubmed: 18662804
Bone Marrow Transplant. 2019 Jun;54(6):911-912
pubmed: 30401966
Transplantation. 2016 Oct;100(10):e74-80
pubmed: 27495775
Mediterr J Hematol Infect Dis. 2019 Jan 01;11(1):e2019001
pubmed: 30671207
Clin Microbiol Rev. 2010 Oct;23(4):689-712
pubmed: 20930070
Antimicrob Agents Chemother. 2001 Oct;45(10):2775-80
pubmed: 11557468
BMC Infect Dis. 2019 May 8;19(1):388
pubmed: 31068147
Transpl Infect Dis. 2021 Jun;23(3):e13515
pubmed: 33210830
Am J Transplant. 2018 Dec;18(12):3060-3064
pubmed: 30286286
Antimicrob Agents Chemother. 2015 Oct;59(10):6588-93
pubmed: 26259791
Transplantation. 2018 Jun;102(6):900-931
pubmed: 29596116
Antiviral Res. 2014 Nov;111:8-12
pubmed: 25194992
N Engl J Med. 2017 Dec 21;377(25):2433-2444
pubmed: 29211658
Antimicrob Agents Chemother. 2014;58(1):610-3
pubmed: 24189264