{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:53:22Z","timestamp":1792810402137,"version":"4.5.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2023,7,3]]},"abstract":"\n Importance<\/jats:title>\n Valganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Randomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022).<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized in a 1:1 ratio (stratified by receipt of lymphocyte-depleting induction immunosuppression) to receive letermovir, 480 mg, orally daily (with acyclovir) or valganciclovir, 900 mg, orally daily (adjusted for kidney function) for up to 200 days after transplant, with matching placebos.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was CMV disease, confirmed by an independent masked adjudication committee, through posttransplant week 52 (prespecified noninferiority margin, 10%). CMV disease through week 28 and time to onset of CMV disease through week 52 were secondary outcomes. Exploratory outcomes included quantifiable CMV DNAemia and resistance. The rate of leukopenia or neutropenia through week 28 was a prespecified safety outcome.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 601 participants randomized, 589 received at least 1 dose of the study drug (mean age, 49.6 years; 422 [71.6%] men). Letermovir (n\u2009=\u2009289) was noninferior to valganciclovir (n\u2009=\u2009297) for prevention of CMV disease through week 52 (10.4% vs 11.8% of participants with committee-confirmed CMV disease; stratum-adjusted difference \u22121.4% [95% CI, \u22126.5% to 3.8%]). No participants who received letermovir vs 5 participants (1.7%) who received valganciclovir developed CMV disease through week 28. Time to onset of CMV disease was comparable between the groups (hazard ratio, 0.90 [95% CI, 0.56-1.47]). Quantifiable CMV DNAemia was detected in 2.1% of participants in the letermovir group vs 8.8% in the valganciclovir group by week 28. Of participants evaluated for suspected CMV disease or CMV DNAemia, none (0\/52) who received letermovir and 12.1% (8\/66) who received valganciclovir had resistance-associated substitutions. The rate of leukopenia or neutropenia through week 28 was lower with letermovir vs valganciclovir (26% vs 64%; difference, \u221237.9% [95% CI, \u221245.1% to \u221230.3%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Fewer participants in the letermovir group than the valganciclovir group discontinued prophylaxis due to adverse events (4.1% vs 13.5%) or drug-related adverse events (2.7% vs 8.8%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n Among adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03443869<\/jats:ext-link>\n ;\n EudraCT: 2017-001055-30<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2023.9106","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T20:40:13Z","timestamp":1686084013000},"page":"33","source":"Crossref","is-referenced-by-count":207,"title":["Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients"],"prefix":"10.1001","volume":"330","author":[{"given":"Ajit P.","family":"Limaye","sequence":"first","affiliation":[{"name":"Division of Allergy & Infectious Diseases, Departments of Medicine & Laboratory Medicine and Pathology, University of Washington Medicine, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Budde","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Humar","sequence":"additional","affiliation":[{"name":"Ajmera Transplant Center, University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Vincenti","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk R. J.","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium"},{"name":"Department of Nephrology and Renal Transplantation, UZ Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Department of Health Sciences, University of South Australia, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Stauffer","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Murata","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Strizki","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie L.","family":"Teal","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Haber","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"6","key":"joi230064r1","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1097\/TP.0000000000002191","article-title":"The third International Consensus Guidelines on the management of cytomegalovirus in solid-organ transplantation.","volume":"102","author":"Kotton","year":"2018","journal-title":"Transplantation"},{"issue":"6","key":"joi230064r2","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s11908-012-0292-2","article-title":"Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment.","volume":"14","author":"Beam","year":"2012","journal-title":"Curr Infect Dis Rep"},{"issue":"2","key":"joi230064r3","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1016\/j.ajt.2023.02.004","article-title":"OPTN\/SRTR 2021 annual data report: kidney.","volume":"23","author":"Lentine","year":"2023","journal-title":"Am J Transplant"},{"issue":"5","key":"joi230064r4","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1111\/j.1600-6143.2010.03074.x","article-title":"The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients.","volume":"10","author":"Humar","year":"2010","journal-title":"Am J Transplant"},{"issue":"4","key":"joi230064r5","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1111\/j.1600-6143.2004.00382.x","article-title":"Efficacy and safety of valganciclovir vs oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.","volume":"4","author":"Paya","year":"2004","journal-title":"Am J Transplant"},{"issue":"1","key":"joi230064r8","doi-asserted-by":"publisher","DOI":"10.1111\/tid.v25.1","article-title":"Burden of neutropenia and leukopenia among adult kidney transplant recipients: a systematic literature review of observational studies.","volume":"25","author":"Raval","year":"2023","journal-title":"Transpl Infect Dis"},{"issue":"S1","key":"joi230064r9","doi-asserted-by":"publisher","first-page":"S776","DOI":"10.1093\/ofid\/ofab466.1572","article-title":"Real-world effectiveness and complications of valganciclovir (VGC) prophylaxis for kidney transplant (KT) recipients at high risk for cytomegalovirus (CMV) infection (CMV donor (D)+\/recipient (R)-).","volume":"8","author":"Roumpz","year":"2021","journal-title":"Open Forum Infect Dis"},{"issue":"4","key":"joi230064r10","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1093\/ckj\/sfx145","article-title":"High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation.","volume":"11","author":"Rissling","year":"2018","journal-title":"Clin Kidney J"},{"issue":"3","key":"joi230064r11","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02684-21","article-title":"Detection of ganciclovir-resistant cytomegalovirus in a prospective cohort of kidney transplant recipients receiving subtherapeutic valganciclovir prophylaxis.","volume":"10","author":"Wong","year":"2022","journal-title":"Microbiol Spectr"},{"issue":"2","key":"joi230064r12","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.transproceed.2017.09.058","article-title":"Resistant cytomegalovirus infection after renal transplantation: literature review.","volume":"50","author":"Cintra-Cabrera","year":"2018","journal-title":"Transplant Proc"},{"issue":"7","key":"joi230064r13","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/j.transproceed.2017.02.046","article-title":"Ganciclovir dosing strategies and development of cytomegalovirus resistance in a kidney transplant recipient: a case report.","volume":"49","author":"Echenique","year":"2017","journal-title":"Transplant Proc"},{"issue":"1","key":"joi230064r14","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1093\/cid\/cix259","article-title":"Risk factors and outcomes of ganciclovir-resistant cytomegalovirus infection in solid organ transplant recipients.","volume":"65","author":"Fisher","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"20","key":"joi230064r15","doi-asserted-by":"publisher","first-page":"10884","DOI":"10.1128\/JVI.05265-11","article-title":"The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.","volume":"85","author":"Goldner","year":"2011","journal-title":"J Virol"},{"issue":"1","key":"joi230064r16","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/tri.2013.27.issue-1","article-title":"Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a phase 2a study.","volume":"27","author":"Stoelben","year":"2014","journal-title":"Transpl Int"},{"key":"joi230064r18"},{"issue":"12","key":"joi230064r19","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1111\/ajt.15135","article-title":"Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection.","volume":"18","author":"Cherrier","year":"2018","journal-title":"Am J Transplant"},{"issue":"3","key":"joi230064r20","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02337-18","article-title":"Use of letermovir as salvage therapy for drug-resistant cytomegalovirus retinitis.","volume":"63","author":"Turner","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"joi230064r21","doi-asserted-by":"publisher","DOI":"10.1111\/tid.v23.3","article-title":"Emergence of letermovir resistance in solid organ transplant recipients with ganciclovir resistant cytomegalovirus infection: a case series and review of the literature.","volume":"23","author":"Hofmann","year":"2021","journal-title":"Transpl Infect Dis"},{"issue":"1","key":"joi230064r22","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1186\/s12879-021-06694-4","article-title":"Emergence of Letermovir-resistant HCMV UL56 mutant during rescue treatment in a liver transplant recipient with ganciclovir-resistant infection HCMV: a case report.","volume":"21","author":"Paolucci","year":"2021","journal-title":"BMC Infect Dis"},{"issue":"3","key":"joi230064r23","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1128\/AAC.31.3.361","article-title":"Acyclovir prophylaxis for herpes simplex virus infection.","volume":"31","author":"Gold","year":"1987","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"joi230064r25","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1093\/infdis\/jiz577","article-title":"Letermovir resistance analysis in a clinical trial of cytomegalovirus prophylaxis for hematopoietic stem cell transplant recipients.","volume":"221","author":"Douglas","year":"2020","journal-title":"J Infect Dis"},{"issue":"1","key":"joi230064r26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1093\/cid\/ciw668","article-title":"Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials.","volume":"64","author":"Ljungman","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"2","key":"joi230064r28","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/(ISSN)1097-0258","article-title":"Comparative analysis of two rates.","volume":"4","author":"Miettinen","year":"1985","journal-title":"Stat Med"},{"issue":"6","key":"joi230064r29","doi-asserted-by":"publisher","DOI":"10.1111\/tid.v24.6","article-title":"Cytomegalovirus in the transplant setting: where are we now and what happens next? a report from the International CMV Symposium 2021.","volume":"24","author":"Kotton","year":"2022","journal-title":"Transpl Infect Dis"},{"issue":"9","key":"joi230064r30","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.v33.9","article-title":"Cytomegalovirus in solid organ transplant recipients: guidelines of the American Society of Transplantation Infectious Diseases Community of Practice.","volume":"33","author":"Razonable","year":"2019","journal-title":"Clin Transplant"},{"issue":"25","key":"joi230064r31","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1056\/NEJMoa1706640","article-title":"Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation.","volume":"377","author":"Marty","year":"2017","journal-title":"N Engl J Med"},{"issue":"4","key":"joi230064r33","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.v36.4","article-title":"Outcomes among CMV-mismatched and highly sensitized kidney transplants recipients who develop neutropenia.","volume":"36","author":"Brar","year":"2022","journal-title":"Clin Transplant"},{"key":"joi230064r34","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2022.101677","article-title":"Risk factors for cytomegalovirus infection and disease after kidney transplantation: a meta-analysis.","volume":"74","author":"Tang","year":"2022","journal-title":"Transpl Immunol"},{"issue":"2","key":"joi230064r35","doi-asserted-by":"publisher","DOI":"10.1111\/tid.v23.2","article-title":"Epidemiology, risk factors, and outcomes associated with cytomegalovirus in adult kidney transplant recipients: a systematic literature review of real-world evidence.","volume":"23","author":"Raval","year":"2021","journal-title":"Transpl Infect Dis"},{"key":"joi230064r27","author":"Koch","year":"1990"},{"key":"joi230064r32","author":"Dadwal","year":"2023"},{"key":"joi230064r6","unstructured":"Valcyte (valganciclovir): US prescribing information. Genentech USA, Inc. Accessed January 3, 2023. https:\/\/www.gene.com\/download\/pdf\/valcyte_prescribing.pdf"},{"key":"joi230064r7","unstructured":"Ganciclovir injection: US prescribing information. Sagent Pharmaceuticals, Inc. Accessed January 3, 2023. https:\/\/www.sagentpharma.com\/wp-content\/uploads\/2021\/07\/Ganciclovir_PI_November-2020.pdf"},{"key":"joi230064r17","unstructured":"Prevymis (letermovir): US prescribing information. Merck & Co, Inc. Accessed May 22, 2023. https:\/\/www.merck.com\/product\/usa\/pi_circulars\/p\/prevymis\/prevymis_pi.pdf"},{"key":"joi230064r24","unstructured":"Zovirax (acyclovir): US prescribing information. GlaxoSmithKline. Accessed March 27, 2023. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2005\/018828s030,020089s019,019909s020lbl.pdf"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2805945\/jama_limaye_2023_oi_230064_1690470727.1245.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T11:00:38Z","timestamp":1690542038000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2805945"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2023,7,3]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2023.9106","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7,3]]}}}