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Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: an evidence-based review

Authors El Helou G, Razonable RR

Received 25 January 2019

Accepted for publication 8 April 2019

Published 4 June 2019 Volume 2019:12 Pages 1481—1491


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Professor Suresh Antony

Guy El Helou,1,2 Raymund R Razonable1,2

1Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA; 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA

Abstract: Cytomegalovirus (CMV) is a leading opportunistic infection in immune compromised patients, including allogeneic hematopoietic stem cell (HSCT) or solid organ transplant (SOT) recipients, where primary infection or reactivation is associated with increased morbidity and mortality. Antiviral drugs are the mainstay for the prevention of CMV infection and disease, most commonly with valganciclovir. However, valganciclovir use is often associated with adverse drug reactions, most notably leukopenia and neutropenia, and its widespread use has led to emergence of antiviral resistance. Foscarnet and cidofovir, however, are associated with nephrotoxicity. Letermovir, a novel CMV viral terminase inhibitor drug, was recently approved for CMV prophylaxis in allogeneic HSCT recipients. It has a favorable pharmacokinetic and tolerability profile. The aim of this paper is to review the evidence supporting the use of letermovir in allogeneic HSCT recipients, and how the drug impacts our contemporary clinical practice. In addition, we discuss the ongoing clinical trial of letermovir for the prevention of CMV in SOT recipients. The use of letermovir for treatment of CMV infection and disease is not yet approved. However, because of a unique mechanism of activity, we provide our perspective on the potential role of letermovir in the treatment of ganciclovir-resistant CMV infection and disease. Furthermore, drug-resistant CMV has emerged during use of letermovir for prophylaxis and treatment. Caution is advised on its use in order to preserve its therapeutic lifespan.

Keywords: letermovir, valganciclovir, cytomegalovirus, UL56, UL97, transplantation

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