{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:23:44Z","timestamp":1793046224570,"version":"4.5.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":366,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp & Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck & Co., Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI116635"],"award-info":[{"award-number":["AI116635"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 &amp;gt;3 weeks after subjects 2 and 3, respectively, had discontinued LET prophylaxis and received preemptive therapy with ganciclovir.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiz577","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T15:11:34Z","timestamp":1573744294000},"page":"1117-1126","source":"Crossref","is-referenced-by-count":82,"title":["Letermovir Resistance Analysis in a Clinical Trial of Cytomegalovirus Prophylaxis for Hematopoietic Stem Cell Transplant Recipients"],"prefix":"10.1093","volume":"221","author":[{"given":"Cameron M","family":"Douglas","sequence":"first","affiliation":[{"name":"Infectious Disease Research, Merck & Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Barnard","sequence":"additional","affiliation":[{"name":"Infectious Disease Research, Merck & Co., Inc., Kenilworth, New Jersey, 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Doorn","sequence":"additional","affiliation":[{"name":"DDL Diagnostics Laboratory, Rijswijk, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunwen","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Strizki","sequence":"additional","affiliation":[{"name":"Infectious Disease Research, Merck & Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"2020120619053772200_CIT0001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.hoc.2010.11.011","article-title":"Cytomegalovirus in hematopoietic stem cell transplant recipients","volume":"25","author":"Ljungman","year":"2011","journal-title":"Hematol Oncol Clin North 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