{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:40:56Z","timestamp":1777869656007,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transplant Infectious Dis"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Persistent viral replication resulting in ongoing cytomegalovirus (CMV) viremia despite adequate therapy is difficult to manage and associated with negative outcomes. We report a case series of kidney transplant recipients receiving adjunctive letermovir in combination with valganciclovir for refractory CMV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult patients receiving a kidney or kidney\u2010pancreas transplant were included if they developed CMV viremia and initiated letermovir 480\u00a0mg daily as part of a dual therapy regimen with valganciclovir 900\u00a0mg twice daily between 1\/9\/2020 and 31\/12\/2020. Included patients received \u226590 days of valganciclovir and had a detectable viral load less than 1000 Iu\/ml (log<jats:sub>10\u00a0<\/jats:sub>&lt;\u00a03) at the time of letermovir initiation. The primary objective was to evaluate the impact of adjunctive letermovir on viral clearance to negativity. We also evaluated effect of letermovir on tacrolimus levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight patients were included. Letermovir was added 223 \u00b1 105 days after initiation of CMV treatment with ganciclovir derivatives. Median viral load at initiation was 139.7 (range: 73\u2013355) IU\/ml and did not clear or change significantly after 2, 4 and 12\u00a0weeks of adjunctive letermovir (132.5 [range: 34.5\u2013513] IU\/ml vs. 68.7 [range: 34.5\u2013574] IU\/ml vs. 78.3 [range: 34.5\u2013347] IU\/ml, <jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05). Tacrolimus was reduced by \u223c30% in anticipation of a letermovir\u2010tacrolimus drug interaction. Despite this reduction, mean tacrolimus serum levels two weeks after adjunctive letermovir increased by 43% (5.6 \u00b1 1.6\u00a0ng\/ml vs 8.0 \u00b1 4.6\u00a0ng\/ml).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In kidney and kidney\u2010pancreas recipients with refractory CMV, the use of adjunctive letermovir did not result in viral clearance. Additionally, despite a mean tacrolimus dose reduction of 30% at letermovir initiation, serum concentrations increased by over 40%. Further investigation into the optimal approach to refractory CMV is needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tid.13693","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T11:54:35Z","timestamp":1627300475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The addition of adjunctive letermovir to valganciclovir for refractory cytomegalovirus viremia in kidney transplant recipients"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6088-9727","authenticated-orcid":false,"given":"Margaret R.","family":"Jorgenson","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Wisconsin Hospital and Clinics  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1196-5110","authenticated-orcid":false,"given":"Jillian L.","family":"Descourouez","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Wisconsin Hospital and Clinics  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-2168","authenticated-orcid":false,"given":"Neetika","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Nephrology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1667-7465","authenticated-orcid":false,"given":"Sandesh","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Nephrology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3326-8583","authenticated-orcid":false,"given":"Didier A.","family":"Mandelbrot","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Nephrology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-464X","authenticated-orcid":false,"given":"Jon S.","family":"Odorico","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Transplantation University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-981X","authenticated-orcid":false,"given":"Christopher M.","family":"Saddler","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Infectious Diseases University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-6332","authenticated-orcid":false,"given":"Jeannina A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Infectious Diseases University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05265-11"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02337-18"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15135"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002191"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03214-14"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003260"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002785"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13512"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.13489"},{"key":"e_1_2_7_11_1","unstructured":"Cytomegalovirus Antiviral Drug Resistance by Sequencing. ARUP Labs. Accessed May 11 2021.https:\/\/ltd.aruplab.com\/Tests\/Pub\/2004760."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.13570"},{"key":"e_1_2_7_13_1","unstructured":"Letermovir Versus Valganciclovir to Prevent Human Cytomegalovirus Disease in Kidney Transplant Recipients (MK\u20108228\u2010002). Merck Sharp & Dohme Corp. ClinicalTrials.gov Identifier: NCT03443869.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03443869. Accessed May 18 2021."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002886"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.13166"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2021.02.001"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-020-03990-w"},{"issue":"7","key":"e_1_2_7_18_1","article-title":"Suppression of CMV infection with letermovir in a kidney transplant patient","volume":"7","author":"Koepf US","year":"2020","journal-title":"Eur J Case Rep Intern Med"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12225"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03530.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31828555ac"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1423"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02173-07"}],"container-title":["Transplant Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tid.13693","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/tid.13693","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tid.13693","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T11:17:36Z","timestamp":1693221456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tid.13693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/tid.13693"],"URL":"https:\/\/doi.org\/10.1111\/tid.13693","archive":["Portico"],"relation":{},"ISSN":["1398-2273","1399-3062"],"issn-type":[{"value":"1398-2273","type":"print"},{"value":"1399-3062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]},"assertion":[{"value":"2021-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13693"}}