{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:39:54Z","timestamp":1770885594095,"version":"3.50.1"},"reference-count":25,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human herpesvirus 6B (HHV-6B) frequently reactivates after allogeneic hematopoietic cell transplantation (HCT). There are no randomized studies of antiviral treatments to prevent HHV-6B reactivation. Brincidofovir has high in vitro activity against HHV-6B and other DNA viruses, but its in vivo activity for HHV-6B has not been demonstrated. We performed a post hoc analysis of a randomized controlled trial of twice-weekly oral brincidofovir for cytomegalovirus prophylaxis after allogeneic HCT to study the effect of brincidofovir on HHV-6B reactivation. We included patients randomized within 2 weeks of HCT and who received at least 6 consecutive doses of study drug after randomization. We tested plasma for HHV-6B through week 6 post-HCT. The cohort consisted of 92 patients receiving brincidofovir and 61 receiving placebo. The cumulative incidence of HHV-6B plasma detection through day 42 post-HCT was significantly lower among patients receiving brincidofovir (14.2%) compared with placebo (32.4%; log-rank, 0.019). In an adjusted Cox model, brincidofovir exposure remained associated with a lower hazard for HHV-6B plasma detection (hazard ratio, 0.40; 95% confidence interval, 0.20-0.80). In conclusion, brincidofovir prophylaxis reduced HHV-6B reactivation after allogeneic HCT in a post hoc analysis of a randomized controlled trial. These data support the study of intravenous brincidofovir for HHV-6B prophylaxis.<\/jats:p>","DOI":"10.1182\/blood.2019004315","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T01:29:33Z","timestamp":1582162173000},"page":"1447-1451","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT"],"prefix":"10.1182","volume":"135","author":[{"given":"Joshua A.","family":"Hill","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA;"},{"name":"Department of Medicine, University of Washington, Seattle, WA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Garrett","family":"Nichols","sequence":"first","affiliation":[{"name":"Chimerix, Durham, NC;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-8734","authenticated-orcid":false,"given":"Francisco M.","family":"Marty","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA;"},{"name":"Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genovefa A.","family":"Papanicolaou","sequence":"first","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Brundage","sequence":"first","affiliation":[{"name":"Chimerix, Durham, NC;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall","family":"Lanier","sequence":"first","affiliation":[{"name":"Chimerix, Durham, NC;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle M.","family":"Zerr","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA;"},{"name":"Department of Pediatrics, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Boeckh","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA;"},{"name":"Department of Medicine, University of Washington, Seattle, WA;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"issue":"11","key":"2020042311583474300_B1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/bmt.2017.175","article-title":"Clinical characteristics and outcome of human herpesvirus-6 encephalitis after allogeneic hematopoietic stem cell transplantation","volume":"52","author":"Ogata","year":"2017","journal-title":"Bone Marrow Transplant"},{"issue":"8","key":"2020042311583474300_B2","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/s41409-019-0457-9","article-title":"Virus detection in the cerebrospinal fluid of hematopoietic stem cell transplant recipients is associated with poor patient outcomes: a CIBMTR contemporary longitudinal study","volume":"54","author":"Abidi","year":"2019","journal-title":"Bone Marrow Transplant"},{"issue":"4","key":"2020042311583474300_B3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/bmt.2012.180","article-title":"HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis","volume":"48","author":"Scheurer","year":"2013","journal-title":"Bone Marrow Transplant"},{"issue":"16","key":"2020042311583474300_B4","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1182\/blood-2016-10-748426","article-title":"The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality","volume":"129","author":"Hill","year":"2017","journal-title":"Blood"},{"issue":"11","key":"2020042311583474300_B5","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1016\/j.bbmt.2018.04.021","article-title":"Human Herpesvirus-6B reactivation is a risk factor for grades II to IV acute graft-versus-host disease after hematopoietic stem cell transplantation: a systematic review and meta-analysis","volume":"24","author":"Phan","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"issue":"1","key":"2020042311583474300_B6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1164\/rccm.201809-1635OC","article-title":"First onset herpesviral infection and lung injury in allogeneic hematopoietic cell transplantation","volume":"200","author":"Zhou","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"issue":"29","key":"2020042311583474300_B7","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1200\/JCO.19.00908","article-title":"Human herpesvirus 6B and lower respiratory tract disease after hematopoietic cell transplantation","volume":"37","author":"Hill","year":"2019","journal-title":"J Clin Oncol"},{"issue":"6","key":"2020042311583474300_B8","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1097\/DAD.0b013e31825667ed","article-title":"Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation","volume":"34","author":"Roux","year":"2012","journal-title":"Am J Dermatopathol"},{"issue":"6","key":"2020042311583474300_B9","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.jaci.2016.12.992","article-title":"Viral reactivations and associated outcomes in the context of immune reconstitution after pediatric hematopoietic cell transplantation","volume":"140","author":"Admiraal","year":"2017","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"2020042311583474300_B10","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1182\/bloodadvances.2017012724","article-title":"Human herpesvirus 6 viremia affects T-cell reconstitution after allogeneic hematopoietic stem cell transplantation","volume":"2","author":"de Koning","year":"2018","journal-title":"Blood Adv"},{"issue":"1","key":"2020042311583474300_B11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/bmt.2008.268","article-title":"Primary infection of human herpesvirus-6 in an infant who received cord blood SCT","volume":"43","author":"Muramatsu","year":"2009","journal-title":"Bone Marrow Transplant"},{"issue":"1","key":"2020042311583474300_B12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1399-3062.2011.00662.x","article-title":"Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation","volume":"14","author":"Ishiyama","year":"2012","journal-title":"Transpl Infect Dis"},{"issue":"2","key":"2020042311583474300_B13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/bmt.2012.121","article-title":"Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis","volume":"48","author":"Ogata","year":"2013","journal-title":"Bone Marrow Transplant"},{"issue":"6","key":"2020042311583474300_B14","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.bbmt.2018.02.008","article-title":"Effects of prophylactic foscarnet on human herpesvirus-6 reactivation and encephalitis in cord blood transplant recipients: a prospective multicenter trial with an historical control group","volume":"24","author":"Ogata","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"issue":"3","key":"2020042311583474300_B15","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/sj.bmt.1705907","article-title":"Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy after allogeneic stem cell transplantation: a prospective evaluation","volume":"41","author":"Ogata","year":"2008","journal-title":"Bone Marrow Transplant"},{"issue":"6","key":"2020042311583474300_B16","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/bmt.2010.201","article-title":"Preemptive therapy of human herpesvirus-6 encephalitis with foscarnet sodium for high-risk patients after hematopoietic SCT","volume":"46","author":"Ishiyama","year":"2011","journal-title":"Bone Marrow Transplant"},{"key":"2020042311583474300_B17","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.antiviral.2019.01.008","article-title":"In vitro comparison of currently available and investigational antiviral agents against pathogenic human double-stranded DNA viruses: A systematic literature review","volume":"163","author":"Chemaly","year":"2019","journal-title":"Antiviral Res"},{"issue":"10","key":"2020042311583474300_B18","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1086\/656717","article-title":"Efficacy of CMX001 against herpes simplex virus infections in mice and correlations with drug distribution studies","volume":"202","author":"Quenelle","year":"2010","journal-title":"J Infect Dis"},{"issue":"2","key":"2020042311583474300_B19","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.bbmt.2018.09.038","article-title":"A randomized, double-blind, placebo-controlled phase 3 trial of oral brincidofovir for cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplantation","volume":"25","author":"Marty","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"issue":"11","key":"2020042311583474300_B20","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.bbmt.2012.04.016","article-title":"Cord-blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus-6-associated acute limbic encephalitis: a cohort analysis","volume":"18","author":"Hill","year":"2012","journal-title":"Biol Blood Marrow Transplant"},{"issue":"5","key":"2020042311583474300_B21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/cid\/cit358","article-title":"Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study","volume":"57","author":"Ogata","year":"2013","journal-title":"Clin Infect Dis"},{"issue":"3","key":"2020042311583474300_B22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/rmv.715","article-title":"Chromosomally integrated human herpesvirus 6: questions and answers","volume":"22","author":"Pellett","year":"2012","journal-title":"Rev Med Virol"},{"key":"2020042311583474300_B23","volume-title":"Poster presented at the American Association of Pharmaceutical Scientists Annual Meeting and Exposition","author":"Tippin"},{"issue":"1","key":"2020042311583474300_B24","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.bbmt.2011.07.018","article-title":"The complex relationship between human herpesvirus 6 and acute graft-versus-host disease","volume":"18","author":"Pichereau","year":"2012","journal-title":"Biol Blood Marrow Transplant"},{"issue":"suppl_1","key":"2020042311583474300_B25","doi-asserted-by":"crossref","first-page":"S311","DOI":"10.1093\/ofid\/ofx163.725","article-title":"Pharmacokinetics (PK) and safety of intravenous (IV) brincidofovir (BCV) in healthy adult subjects","volume":"4","author":"Wire","year":"2017","journal-title":". Open Forum Infect. Dis"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/135\/17\/1447\/1724648\/bloodbld2019004315.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/135\/17\/1447\/1724648\/bloodbld2019004315.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T15:59:18Z","timestamp":1587657558000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/135\/17\/1447\/452524\/Oral-brincidofovir-decreases-the-incidence-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,23]]},"references-count":25,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2020,4,23]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2019004315","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,23]]}}}