Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection.

08:00 EDT 4th October 2018 | BioPortfolio

Summary of "Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection."

Following a year of valganciclovir prophylaxis, a lung transplant recipient developed cytomegalovirus (CMV) infection that became resistant to ganciclovir, as confirmed by detection of UL97 kinase mutation M460V and a previously uncharacterized UL54 DNA polymerase mutation L516P. The latter mutation is now shown to confer ganciclovir and cidofovir resistance. As predicted from the viral genotype, foscarnet therapy was effective, but resumption of valganciclovir as secondary prophylaxis resulted in a plasma viral load rebound to 3.6 log copies/mL several weeks later. Valganciclovir was then replaced by letermovir, resulting in gradual viral load reduction in the first 5 weeks to below the quantitation limit (2.7 log copies/mL) for one week, followed by 10 weeks of rising viral loads reaching 4.3 log copies/mL while on letermovir. At this point, CMV genotypic testing revealed UL56 mutation C325Y, which confers absolute resistance to letermovir. Retreatment with foscarnet was successful. This case adds to the considerable list of proven ganciclovir resistance mutations, and provides an early experience with letermovir resistance after off-label therapeutic use. This experience is consistent with in vitro observations of rapid emergence of letermovir-resistant CMV after drug exposure. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143


DeepDyve research library

PubMed Articles [11087 Associated PubMed Articles listed on BioPortfolio]

Donor Lung Sequence Number and Survival after Lung Transplantation in the United States.

In the United States, an algorithm known as the 'match-run' creates an ordered ranking of potential recipients for available lung allografts. A recipient's match-run position, or 'sequence number,' is...

Double-lung versus heart-lung transplantation for pre-capillary pulmonary arterial hypertension; A 24-year single-center retrospective study.

Transplant type for end-stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart-lung(HLT) versus double-lung(DLT) transplantation.

Detection of engraftment of donor-derived antibody producing cells in a lung transplant recipient by anti-cytomegalovirus IgG avidity test.

Transplant recipients become immunocompromised through the use of immunosuppressive therapy to prevent allograft rejection. These recipients readily experience human cytomegalovirus (CMV) infection or...

HLA class II Eplet mismatch predicts De Novo DSA formation post lung transplant.

The use of algorithms such as HLAMatchmaker to redefine donor-recipient HLA matching is gaining increasing attention. Our research has previously demonstrated that higher HLA class II eplet mismatches...

Clinical development of letermovir and maribavir: Overview of human cytomegalovirus drug resistance.

The prevention and treatment of human cytomegalovirus (HCMV) infections is based on the use of antiviral agents that currently target the viral DNA polymerase and that may cause serious side effects. ...

Clinical Trials [10017 Associated Clinical Trials listed on BioPortfolio]

Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK-8228-002)

The primary objective of this study is to evaluate the efficacy of letermovir (LET) versus valganciclovir (VGCV) in preventing CMV disease in adult kidney transplant recipients. The primar...

Advanced Immunoclinical Phenotyping of Rejection in Lung Transplant

Chronic allograft rejection of the transplanted lung (CLAD) is a major health issue in patients after lung transplant. This study is a registry-forming study with concurrent tissue banking...

Emergence of Gram-negative Resistance in Blood Culture Isolates of Solid-organ Transplant Recipients

The information collected will provide insight in to the epidemiology of antibiotic resistance in a transplant compared to a non-transplant population. Data is needed regarding the date of...

Ganciclovir by Infusion and by Mouth in Treating Patients With Cytomegalovirus After Donor Bone Marrow Transplant

RATIONALE: Antiviral drugs, such as ganciclovir, act against viruses. Giving ganciclovir by infusion and then by mouth may be effective treatment for cytomegalovirus that has become active...

A Relative Bioavailability Study of Valcyte (Valganciclovir) in Lung Transplant Recipients With or Without Cystic Fibrosis.

This study will assess the relative bioavailability of ganciclovir from the pro-drug valganciclovir in lung transplant recipients with or without cystic fibrosis. Each patient will receive...

Medical and Biotech [MESH] Definitions

An ACYCLOVIR analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.

An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.

RESPIRATORY MUSCLE contraction during INHALATION. The work is accomplished in three phases: LUNG COMPLIANCE work, that required to expand the LUNGS against its elastic forces; tissue resistance work, that required to overcome the viscosity of the lung and chest wall structures; and AIRWAY RESISTANCE work, that required to overcome airway resistance during the movement of air into the lungs. Work of breathing does not refer to expiration, which is entirely a passive process caused by elastic recoil of the lung and chest cage. (Guyton, Textbook of Medical Physiology, 8th ed, p406)

An HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS.

Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.

Quick Search


DeepDyve research library

Relevant Topics

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Searches Linking to this Article