{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:47:32Z","timestamp":1768567652417,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,31]]},"group-title":"HIV\/AIDS","reference-count":42,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Cryptococcal meningitis remains a prominent cause of death in persons with advanced HIV disease. CSF leukocyte infiltration predicts survival at 18 weeks; however, how CSF immune response relates to CSF leukocyte infiltration is unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled 401 adults with HIV-associated cryptococcal meningitis in Uganda who received amphotericin and fluconazole induction therapy. We assessed the association of CSF leukocytes, chemokine, and cytokine responses with 18-week survival.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Participants with CSF leukocytes \u226550\/\u00b5L, had higher probability 68% (52\/77) of 18-week survival compared with 52% (151\/292) 18-week survival in those with \u226450 cells\/\u00b5L (Hazard Ratio=1.63, 95% confidence intervals 1.14-2.23; p=0.008). Survival was also associated with higher expression of T helper (Th)-1, Th17 cytokines, and immune regulatory elements. CSF levels of Programmed Death-1 Ligand, CXCL10, and Interleukin (IL)-2 independently predicted survival. In multivariate analysis, CSF leukocytes were inversely associated with CSF fungal burden and positively associated with CSF protein, interferon-gamma (IFN-\u03b3), IL-17A, tumor necrosis factor (TNF)-\u03b1, and peripheral blood CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells expression.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    18-week survival after diagnosis of cryptococcal meningitis was associated with higher CSF leukocytes at baseline with greater T helper 1 (IFN-\u03b3, IL-2 and TNF-\u03b1 cytokines), T helper 17 (IL-17A cytokine) and CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    T cell (CXCL10 chemokine) responses. These results highlight the interdependent contribution of soluble and cellular immune responses in predicting survival with HIV-associated cryptococcal meningitis.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.05.29.24308130","type":"posted-content","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T11:10:43Z","timestamp":1717153843000},"source":"Crossref","is-referenced-by-count":0,"title":["Impact of Cerebrospinal Fluid Leukocyte Infiltration and Neuroimmmune Mediators on Survival with HIV-Associated Cryptococcal Meningitis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-8687","authenticated-orcid":false,"given":"Samuel","family":"Okurut","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-0060","authenticated-orcid":false,"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-5598","authenticated-orcid":false,"given":"Yukari C.","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-1545","authenticated-orcid":false,"given":"Lillian","family":"Tugume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0000-8876","authenticated-orcid":false,"given":"Caleb P.","family":"Skipper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8125-0698","authenticated-orcid":false,"given":"Kenneth","family":"Ssebambulidde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-9646","authenticated-orcid":false,"given":"Joshua","family":"Rhein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2410-5344","authenticated-orcid":false,"given":"Abdu K.","family":"Musubire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Akampurira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Okafor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5148-8876","authenticated-orcid":false,"given":"Joseph O.","family":"Olobo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2702-5729","authenticated-orcid":false,"given":"Edward N.","family":"Janoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-0321","authenticated-orcid":false,"given":"David 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B cell responses, immune modulation, and survival among patients with HIV-associated cryptococcal meningitis. Doctoral thesis, Makerere University. 2023."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.05.29.24308130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:02:07Z","timestamp":1768507327000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2024.05.29.24308130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":42,"URL":"https:\/\/doi.org\/10.1101\/2024.05.29.24308130","relation":{},"subject":[],"published":{"date-parts":[[2024,5,31]]},"subtype":"preprint"}}