{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T22:47:23Z","timestamp":1793573243089,"version":"4.5.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003605","name":"Korea International Cooperation Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003605","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TB Alliance"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Previously, drug-resistant tuberculosis (DR-TB) patients were treated with long, toxic, and relatively ineffective regimens. However, in recent years, there have been major improvements made. The 2020 World Health Organization DR-TB Treatment guidelines recommended the use of a 6-months all-oral BPaL (bedaquiline, pretomanid and linezolid) regimen under operational research (OR) conditions for selected DR-TB patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The processes, challenges, and interim results of introducing BPaL under OR conditions in 7 countries supported under the Korea International Cooperation Agency\/TB Alliance-funded \u201cLeveraging Innovation for Faster Treatment of Tuberculosis (LIFT-TB)\u201d project are described here. The OR objectives were to explore the feasibility of introducing the BPaL regimen, and to estimate its effectiveness and safety in a select group of DR-TB patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Between November 2020 and the end of March 2023, a total of 574 patients had been enrolled. Interim treatment success stands at an encouraging 90.9% (280\/308). Although adverse events of special interest (AESI) were common, they were manageable, and only 1 patient had to discontinue the complete BPaL treatment regimen. In addition, no unexpected adverse events (AE) were seen.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>With careful advocacy, frequent communication with partners, and following steps to strengthen essential aspects of the delivery system, the project\u2019s experiences show that BPaL OR was feasible across different country settings. Project documents were constantly updated. The sharing of information, experiences, and interim results had a significant positive and motivating effect within and across countries. Interim OR results show excellent patient responses and are comparable to those seen under trial conditions. Although common, the observed AEs and AESIs were manageable, and no unexpected AEs were seen.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0310773","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T18:35:41Z","timestamp":1732041341000},"page":"e0310773","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Introducing BPaL: Experiences from countries supported under the LIFT-TB project"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-9965","authenticated-orcid":true,"given":"D. F.","family":"Wares","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mbenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Mirtskhulava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Quelapio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Slyzkyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Koppelaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. N.","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Go","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.-K.","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Everitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Foraida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Diachenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Juneja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Burhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Totkogonova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Myint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. A.","family":"Lytvynenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Parpieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. V.","family":"Nhung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Gebhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"pone.0310773.ref001","doi-asserted-by":"crossref","DOI":"10.30875\/b75dea7e-en","volume-title":"Global TB report, 2021.","author":"World Health Organization (WHO)","year":"2021"},{"key":"pone.0310773.ref002","volume-title":"Global TB report, 2022.","author":"World Health Organization","year":"2022"},{"key":"pone.0310773.ref003","volume-title":"WHO treatment guidelines for drug-resistant tuberculosis. 2016 update","author":"World Health Organization","year":"2016"},{"key":"pone.0310773.ref004","volume-title":"Rapid Communication: Key changes to the treatment of DR-TB","author":"World Health Organization","year":"2018"},{"issue":"10","key":"pone.0310773.ref005","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1056\/NEJMoa1901814","article-title":"Treatment of highly drug-resistant pulmonary tuberculosis","volume":"382","author":"F Conradie","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0310773.ref006","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/S0140-6736(06)69573-1","article-title":"Extensively drug-resistant TB as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa","volume":"368","author":"NR Gandhi","year":"2006","journal-title":"Lancet"},{"key":"pone.0310773.ref007","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3201\/eid1903.120998","article-title":"Treatment outcomes for extensively drug-resistant tuberculosis and HIV co-infection","volume":"19","author":"MR O\u2019Donnell","year":"2013","journal-title":"Emerg Infect Dis"},{"key":"pone.0310773.ref008","volume-title":"WHO consolidated guidelines on tuberculosis. Module 4: Treatment. Drug-resistant TB treatment","author":"World Health Organization","year":"2020"},{"key":"pone.0310773.ref009","unstructured":"LIFT-TB project website accessible at https:\/\/www.lifttb.org."},{"key":"pone.0310773.ref010","doi-asserted-by":"crossref","first-page":"e007182","DOI":"10.1136\/bmjgh-2021-007182","article-title":"Budgetary impact of using BPaL for treating extensively drug- resistant TB","volume":"7","author":"C Mulder","year":"2022","journal-title":"BMJ Global Health"},{"key":"pone.0310773.ref011","unstructured":"TB Alliance. A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Drug Resistant Pulmonary Tuberculosis. https:\/\/www.tballiance.org\/portfolio\/trial\/5089. Full Text available via ClinicalTrials.gov"},{"key":"pone.0310773.ref012","unstructured":"TB Alliance. Safety and Efficacy of Various Doses and Treatment Durations of Linezolid Plus Bedaquiline and Pretomanid in Participants with Pulmonary, XDR-TB, Pre- XDR-TB or Non -responsive\/Intolerant MDR-TB (ZeNix-TB). https:\/\/www.tballiance.org\/portfolio\/trial\/11883. Full Text available via ClinicalTrials.gov"},{"issue":"9","key":"pone.0310773.ref013","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1056\/NEJMoa2119430","article-title":"Bedaquiline\u2013Pretomanid\u2013Linezolid Regimens for Drug-Resistant TB","volume":"387","author":"F Conradie","year":"2022","journal-title":"N Engl J Med"},{"key":"pone.0310773.ref014","unstructured":"KNCV TB Foundation\u2019s \u201cGeneric BPaL OR Protocol\u201d available via https:\/\/www.lifttb.org\/resources"},{"issue":"10","key":"pone.0310773.ref015","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.5588\/ijtld.19.0790","article-title":"Introducing bedaquiline: experience from the Challenge TB project","volume":"24","author":"CG Edwards","year":"2020","journal-title":"Int J Tuberc Lung Dis"},{"issue":"3","key":"pone.0310773.ref016","doi-asserted-by":"crossref","first-page":"190","DOI":"10.5588\/pha.16.0037","article-title":"The experience of bedaquiline implementation at a decentralized clinic in South Africa.","volume":"6","author":"R Cariem","year":"2016","journal-title":"Public Health Action"},{"key":"pone.0310773.ref017","volume-title":"Framework for implementation. WHO\/HTM\/TB\/2015.28","author":"World Health Organization","year":"2015"},{"key":"pone.0310773.ref018","unstructured":"GRADE working group website: https:\/\/www.gradeworkinggroup.org\/."},{"key":"pone.0310773.ref019","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1056\/NEJMoa2117166","article-title":"A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis","volume":"387","author":"B-T Nyang\u2019wa","year":"2022","journal-title":"N Engl J Med"},{"issue":"10","key":"pone.0310773.ref020","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1164\/rccm.202107-1779OC","article-title":"An All-Oral 6-Month Regimen for Multidrug-Resistant Tuberculosis A Multicenter, Randomized Controlled Clinical Trial (the NExT Study).","volume":"205","author":"A Esmail","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0310773.ref021","volume-title":"Rapid communication: Key changes to the treatment of drug-resistant tuberculosis.","author":"World Health Organization","year":"2022"},{"key":"pone.0310773.ref022","volume-title":"Module 4: Treatment Drug-resistant tuberculosis treatment 2022 update.","author":"World Health Organization","year":"2022"},{"key":"pone.0310773.ref023","volume-title":"Module 4: Treatment Drug-resistant tuberculosis treatment 2022 update.","author":"World Health Organization","year":"2022"},{"key":"pone.0310773.ref024","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/resp.13143","article-title":"Recent controversies about MDR and XDR-TB: Global implementation of the WHO shorter MDR-TB regimen and bedaquiline for all with MDR-TB?","volume":"23","author":"K Dheda","year":"2018","journal-title":"Respirology"},{"key":"pone.0310773.ref025","doi-asserted-by":"crossref","first-page":"714","DOI":"10.3390\/antibiotics12040714","article-title":"Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis","volume":"12","author":"C Padmapriyadarsini","year":"2023","journal-title":"Antibiotics"},{"key":"pone.0310773.ref026","doi-asserted-by":"crossref","first-page":"1601719","DOI":"10.1183\/13993003.01719-2016","article-title":"Rapid emergence of Mycobacterium tuberculosis bedaquiline resistance: lessons to avoid repeating past errors","volume":"49","author":"N Veziris","year":"2017","journal-title":"Eur Respir J"},{"key":"pone.0310773.ref027","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1164\/rccm.201605-1065LE","article-title":"Reply: call for regular susceptibility testing of bedaquiline and delamanid","volume":"194","author":"H Hoffman","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"pone.0310773.ref028","first-page":"1","article-title":"Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model","volume":"67","author":"Si-Yang Li","year":"2023","journal-title":"Antimicrob Agents Chemother"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T18:35:56Z","timestamp":1732041356000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310773"}},"subtitle":[],"editor":[{"given":"Shahriar","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0310773","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,19]]}}}