{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:17:52Z","timestamp":1793755072674,"version":"4.6.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T00:00:00Z","timestamp":1724457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"US National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01 NS086312"],"award-info":[{"award-number":["R01 NS086312"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"US National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["K23 NS110470"],"award-info":[{"award-number":["K23 NS110470"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43 TW009345"],"award-info":[{"award-number":["D43 TW009345"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute for Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI170158"],"award-info":[{"award-number":["R01 AI170158"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23 AI138851"],"award-info":[{"award-number":["K23 AI138851"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["203905\/Z\/16\/Z"],"award-info":[{"award-number":["203905\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","award":["NIHR-RP-2017-08-ST2-012"],"award-info":[{"award-number":["NIHR-RP-2017-08-ST2-012"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","award":["NIHR134342"],"award-info":[{"award-number":["NIHR134342"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013986","name":"United Kingdom Government","doi-asserted-by":"publisher","award":["TRIA2015-1092"],"award-info":[{"award-number":["TRIA2015-1092"]}],"id":[{"id":"10.13039\/100013986","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004441","name":"Swedish International Development Cooperation Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004441","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Department of Health and Social Care"},{"name":"UK Foreign Commonwealth and Development Office"},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust via the Joint Global Health Trials","award":["MR\/P006922\/1"],"award-info":[{"award-number":["MR\/P006922\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In 2022, the World Health Organization (WHO) recommended a single 10\u2005mg\/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022\u20132023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During 2022\u20132023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95% confidence interval [CI]: 61.6%\u201376.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95% CI: 65.2%\u201378.8%; absolute risk difference = \u22123.1%; 95% CI: \u221213.1% to 6.9%; P = .61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU\/mL\/day; P = .80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4\/144).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciae413","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T23:37:29Z","timestamp":1724369849000},"page":"417-424","source":"Crossref","is-referenced-by-count":10,"title":["Implementation of Single High-dose Liposomal Amphotericin B Based Induction Therapy for Treatment of HIV-associated Cryptococcal Meningitis in Uganda: A Comparative Prospective Cohort Study"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-4887","authenticated-orcid":false,"given":"Jane","family":"Gakuru","sequence":"first","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0291-651X","authenticated-orcid":false,"given":"Enock","family":"Kagimu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyue","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Okurut","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Nsangi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan C","family":"Bahr","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Okirwoth","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivie C","family":"Namuju","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]},{"name":"Botswana Harvard Health Partnership , Gaborone ,","place":["Botswana"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]},{"name":"Botswana Harvard Health Partnership , Gaborone ,","place":["Botswana"]},{"name":"School of Pathology, Faculty of Health Sciences, University of the Witwatersrand , Johannesburg ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Ahimbisibwe","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne","family":"Ellis","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]},{"name":"Clinical Research Department, London School of Hygiene and Tropical Medicine , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kizza Kandole","family":"Tadeo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-0060","authenticated-orcid":false,"given":"David R","family":"Boulware","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-0321","authenticated-orcid":false,"given":"David B","family":"Meya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]},{"name":"Division of Infectious Diseases & International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]},{"name":"College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"Tugume","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,24]]},"reference":[{"key":"2025022409340502600_ciae413-B1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11046-020-00512-2","article-title":"HIV-associated cryptococcal meningitis patients treated with amphotericin B deoxycholate plus flucytosine under routine care conditions in a referral center in Sao Paulo, 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cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy","volume":"46","author":"Kambugu","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2025022409340502600_ciae413-B5","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1056\/NEJMoa2111904","article-title":"Single-dose liposomal amphotericin B treatment for cryptococcal meningitis","volume":"386","author":"Jarvis","year":"2022","journal-title":"N Engl J Med"},{"key":"2025022409340502600_ciae413-B6","doi-asserted-by":"crossref","first-page":"e1845","DOI":"10.1016\/S2214-109X(22)00450-8","article-title":"Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial","volume":"10","author":"Lawrence","year":"2022","journal-title":"Lancet Glob 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trial","volume":"19","author":"Lawrence","year":"2018","journal-title":"Trials"},{"key":"2025022409340502600_ciae413-B10","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1093\/cid\/ciac853","article-title":"Recurrence of symptoms following cryptococcal meningitis: characterizing a diagnostic conundrum with multiple etiologies","volume":"76","author":"Bahr","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2025022409340502600_ciae413-B11","author":"Unitaid"},{"key":"2025022409340502600_ciae413-B12","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/cid\/ciu596","article-title":"The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis","volume":"59","author":"Rolfes","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2025022409340502600_ciae413-B13","doi-asserted-by":"crossref","first-page":"ofac416","DOI":"10.1093\/ofid\/ofac416","article-title":"Therapeutic lumbar punctures in human immunodeficiency virus-associated cryptococcal meningitis: should opening pressure direct management?","volume":"9","author":"Kagimu","year":"2022","journal-title":"Open Forum Infect Dis"},{"key":"2025022409340502600_ciae413-B14","doi-asserted-by":"crossref","first-page":"e0000254","DOI":"10.1371\/journal.pgph.0000254","article-title":"Impact of a cryptococcal meningitis diagnosis and treatment program at Lira Regional Referral Hospital in rural, Northern Uganda","volume":"2","author":"Link","year":"2022","journal-title":"PLoS Glob Public Health"},{"key":"2025022409340502600_ciae413-B15","doi-asserted-by":"crossref","first-page":"e759","DOI":"10.1093\/cid\/ciac599","article-title":"Outpatient cryptococcal antigen screening is associated with favorable baseline characteristics and improved survival in persons with cryptococcal meningitis in Uganda","volume":"76","author":"Levin","year":"2023","journal-title":"Clin Infect 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outcomes","volume":"58","author":"Jarvis","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2025022409340502600_ciae413-B19","first-page":"1122","article-title":"Long-term mortality and disability in cryptococcal meningitis: a systematic literature review","volume":"66","author":"Pasquier","year":"2018","journal-title":"Clin Infect Dis"}],"container-title":["Clinical Infectious 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