{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:47:52Z","timestamp":1768567672759,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,12]]},"group-title":"HIV\/AIDS","reference-count":36,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis from being normal to markedly elevated. However, the clinical implications of CSF protein levels in cryptococcal meningitis remain unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analysed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into \u2265100 mg\/dL (n=249) and &lt;100 mg\/dL (n=641). We described baseline clinical variables and mortality by CSF protein levels.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Approximately one-third of individuals had a baseline CSF protein \u2265100 mg\/dL. Those with CSF protein \u2265100 mg\/dL were more likely to present with Glasgow coma scale scores &lt;15 (P&lt;0.01), self-reported seizures at baseline (P=0.02), higher CD4 T-cells (p&lt;0.001), and higher CSF white cells (p&lt;0.001). Moreover, those with a baseline CSF protein \u2265100 mg\/dL also had a lower baseline CSF fungal burden (p&lt;0.001) and a higher percentage of sterile CSF cultures at day 14 (p=0.02). Individuals with CSF protein \u2265100 mg\/dL demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules pro-inflammatory cytokines, type-1 T-helper cell cytokines, type-3 chemokines, and immune-exhaustion marker (p&lt;0.05). 18-week mortality risk in individuals with a CSF protein &lt;100 mg\/dL was 34% higher, (unadjusted Hazard Ratio 1.34; 95% CI, 1.05 to 1.70; p=0.02) than those with \u2265100 mg\/dL.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In cryptococcal meningitis, individuals with CSF protein \u2265100 mg\/dL more frequently presented with seizures, altered mental status, immune activation, and favourable fungal outcomes. Baseline CSF protein levels may serve as a surrogate marker of immune activation and prognosis.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.10.23299793","type":"posted-content","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T11:35:27Z","timestamp":1702380927000},"source":"Crossref","is-referenced-by-count":1,"title":["Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-4052","authenticated-orcid":false,"given":"John","family":"Kasibante","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7748-3598","authenticated-orcid":false,"given":"Eesha","family":"Irfanullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abduljewad","family":"Wele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1495-4596","authenticated-orcid":false,"given":"Elizabeth","family":"Okafor","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\/0000-0002-9292-8687","authenticated-orcid":false,"given":"Samuel","family":"Okurut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enock","family":"Kagimu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Gakuru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris K.","family":"Rutakingirwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8820-288X","authenticated-orcid":false,"given":"Timothy","family":"Mugabi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7526-9504","authenticated-orcid":false,"given":"Edwin","family":"Nuwagira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Jjunju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Mpoza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lillian","family":"Tugume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Nsangi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdu K","family":"Musibire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conrad","family":"Muzoora","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"}]},{"given":"David B.","family":"Meya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-3006","authenticated-orcid":false,"given":"Mahsa","family":"Abassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023121402550718000_2023.12.10.23299793v1.1","unstructured":"UNAIDS. 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