Positive HCMV DNAemia in stem cell recipients undergoing letermovir prophylaxis is expression of abortive infection.

Affiliation

Cassaniti I(1), Colombo AA(2), Bernasconi P(2), Malagola M(3), Russo D(3), Iori AP(4), Girmenia C(4), Greco R(5), Peccatori J(5), Ciceri F(5), Bonifazi F(6), Percivalle E(1), Campanini G(1), Piccirilli G(7), Lazzarotto T(7), Baldanti F(1)(8).
Author information:
(1)Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
(2)Hemopoietic Stem Cell Unit, Division of Haematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
(3)Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, Spedali Civili of Brescia, University of Brescia, Brescia, Italy.
(4)Department of Haematology, Oncology and Dermatology, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy.
(5)Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
(6)Department of Experimental, Diagnostic and Specialty Medicine, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.
(7)Department of Specialized, Experimental, and Diagnostic Medicine, Operative Unit of Clinical Microbiology, St. Orsola Polyclinic, University of Bologna, Bologna, Italy.
(8)Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.

Abstract

Letermovir (LMV) inhibits HCMV replication by binding to components of the HCMV-terminase complex showing a potential role in prevention of HCMV-related complications in allogenic hematopoietic stem cell transplant recipients (allo-HSCTRs). However, little is known about breakthrough HCMV infection and the relevance of HCMV DNAemia during prophylaxis. We reported the results of a multicenter prospective study involving five Italian centers in the management of HCMV DNAemia in 75 adult HCMV-seropositive allo-HSCTRs undergoing LMV prophylaxis. The aim of the present study was to characterize the presence of real HCMV reactivation during LMV prophylaxis. Then, the presence of circulating infectious HCMV particles was determined by virus isolation and degradation of free-floating viral DNA. This report provides the first evidence that during LMV prophylaxis the clinical relevance of HCMV DNAemia should be critically considered.