Journal Article

Emergence of Letermovir-resistant HCMV UL56 mutant during rescue treatment in a liver transplant recipient with ganciclovir-resistant infection HCMV: a case report

Tebaldi, Alessandra, Plebani, Alessandro, Fratini, Alice, Campanini, Giulia, Novazzi, Federica, Baldanti, Fausto, Girelli, Federica, Meini, Antonella, Cassaniti, Irene, Palumbo, Laura, Paolucci, Stefania

2021

Overview

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 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 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Anemia / Antiviral agents / Antiviral drugs / Care and treatment / Case Report / Case reports / Cidofovir / Common variable immunodeficiency / Cytomegalovirus / Cytomegalovirus infections / Diagnosis / Disease prevention / Drug dosages / Drug resistance / Foscarnet / Ganciclovir / HCMV / Hypertension / Hypothyroidism / Immune system / Infectious Diseases / Internal Medicine / Letermovir / Liver / Liver transplantation / Liver transplants / Lymphocytes / Medical Microbiology / Medicine / Medicine & Public Health / Mortality / Mutation / Neutropenia / Parasitology / Patients / Side effects / Staphylococcus infections / Stem cells / Steroids / Toxicity / Transplantation / Tropical Medicine / Viral diseases