{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:03:54Z","timestamp":1785438234673,"version":"3.56.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23AI138851"],"award-info":[{"award-number":["K23AI138851"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Neurologic Disorders","award":["D43TW009345"],"award-info":[{"award-number":["D43TW009345"]}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2TR002492"],"award-info":[{"award-number":["KL2TR002492"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%\u201330% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg\/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (\u22641:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>168 participants enrolled into the ACACIA trial had low plasma CrAg titers (\u22641:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12\/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9\/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60\u20133.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among CrAg-positive persons with low titers (\u22641:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>Clinicaltrials.gov (NCT03945448).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciae266","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:09:45Z","timestamp":1721866185000},"page":"129-136","source":"Crossref","is-referenced-by-count":9,"title":["Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With HIV\u2013Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen Titers"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-0321","authenticated-orcid":false,"given":"David B","family":"Meya","sequence":"first","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]},{"name":"Department of Medicine, School of Medicine, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Nalintya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb P","family":"Skipper","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kirumira","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peruth","family":"Ayebare","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Naluyima","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teopista","family":"Namuli","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Turya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Walukaga","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-4194","authenticated-orcid":false,"given":"Nicole","family":"Engen","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy H","family":"Hullsiek","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abduljewad","family":"Wele","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"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":"David R","family":"Boulware","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, Minnesota 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