{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:04Z","timestamp":1792785844161,"version":"4.5.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"12","funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01NS086312)"],"award-info":[{"award-number":["R01NS086312)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Matinas BioPharma","award":["AI001123"],"award-info":[{"award-number":["AI001123"]}]},{"name":"Matinas BioPharma","award":["AI001124)"],"award-info":[{"award-number":["AI001124)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus\u2013associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with\/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g\/d oral LNC amphotericin through 2 weeks with 100 mg\/kg\/d flucytosine, then 1.2 g\/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg\/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)\/mL\/d for all-oral LNC amphotericin, 0.42 log10 \u00a0Cryptococcus CFU\/mL\/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU\/mL\/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin.<\/jats:p>\n                    <jats:p>Grade 3\u20134 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P = .05), particularly for anemia (21% vs 44%; P = .01) and potassium (5% vs 17%; P = .04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>NCT04031833.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciad440","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T16:25:07Z","timestamp":1690561507000},"page":"1659-1667","source":"Crossref","is-referenced-by-count":76,"title":["Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-0060","authenticated-orcid":false,"given":"David R","family":"Boulware","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mucunguzi","family":"Atukunda","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enock","family":"Kagimu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdu K","family":"Musubire","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Akampurira","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"Tugume","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Ssebambulidde","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"},{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kasibante","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Nsangi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Mugabi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Gakuru","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kimuda","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick","family":"Kasozi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan","family":"Namombwe","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Turyasingura","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris K","family":"Rutakingirwa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Mpoza","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enos","family":"Kigozi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mbarara University of Science and Technology , Mbarara , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad","family":"Muzoora","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mbarara University of Science and Technology , Mbarara , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne","family":"Ellis","sequence":"additional","affiliation":[{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb P","family":"Skipper","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Matkovits","sequence":"additional","affiliation":[{"name":"Matinas Biopharma Nanotechnologies , Bedminster, New Jersey , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R","family":"Williamson","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlisha A","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Fieberg","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy H","family":"Hullsiek","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Abassi","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyue","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B","family":"Meya","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"},{"name":"Infectious Diseases Institute, Makerere University , Kampala , Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"2023121605175181100_ciad440-B1","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S1473-3099(22)00499-6","article-title":"The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis","volume":"22","author":"Rajasingham","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2023121605175181100_ciad440-B2","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: an updated 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