Letermovir Resistance Analysis in a Clinical Trial of Cytomegalovirus Prophylaxis for Hematopoietic Stem Cell Transplant Recipients.
In: Journal of Infectious Diseases, Jg. 221 (2020-03-16), S. 1117-1126
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Zugriff:
Background: Letermovir (LET), a cytomegalovirus (CMV) deoxyribonucleic acid (DNA) terminase inhibitor, was recently approved for prophylaxis of CMV infection in adult CMV-seropositive recipients of allogeneic hematopoietic stem cell transplantation. Cytomegalovirus genotyping was performed to identify LET-resistance-associated variants (RAVs) among subjects in a Phase 3 trial. Methods: The CMV UL56 and UL89 genes, encoding subunits of CMV DNA terminase, were sequenced from plasma collected from subjects with clinically significant CMV infection (CS-CMVi). Novel variants were evaluated by recombinant phenotyping to assess their potential to confer resistance to LET. Results: Genotyping was successful for 50 of 79 LET subjects with CS-CMVi. Resistance-associated variants (encoding pUL56 V236M and C325W) were detected independently in subjects 1 and 3 who experienced CS-CMVi while receiving LET prophylaxis, and 2 other variants (encoding pUL56 E237G and R369T) were detected >3 weeks after subjects 2 and 3, respectively, had discontinued LET prophylaxis and received preemptive therapy with ganciclovir. Conclusions: The detected incidence of CMV resistance among subjects who received LET as prophylaxis in this Phase 3 trial was low. The LET RAVs that were detected mapped to the CMV UL56 gene at positions associated with reduced susceptibility to LET based on resistance selections in cell culture. [ABSTRACT FROM AUTHOR]
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Letermovir Resistance Analysis in a Clinical Trial of Cytomegalovirus Prophylaxis for Hematopoietic Stem Cell Transplant Recipients.
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Autor/in / Beteiligte Person: | Douglas, Cameron M ; Barnard, Richard ; Holder, Daniel ; Leavitt, Randi ; Levitan, Diane ; Maguire, Maureen ; Nickle, David ; Teal, Valerie ; Wan, Hong ; van Alewijk, Dirk C J G ; van Doorn, Leen-Jan ; Chou, Sunwen ; Strizki, Julie |
Zeitschrift: | Journal of Infectious Diseases, Jg. 221 (2020-03-16), S. 1117-1126 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 0022-1899 (print) |
DOI: | 10.1093/infdis/jiz577 |
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