{"doi":"10.1093/infdis/jiaf449","title":"Cerebrospinal Fluid Mononuclear Cell Phenotype and Activation Predictors of 2-Week and 1-Year Survival Among Persons With HIV-Associated Cryptococcal Meningitis","abstract":"BACKGROUND: Despite efforts to optimize therapy for HIV-associated cryptococcal meningitis (CM), survival outcomes remain poor. It is unclear how the cerebrospinal fluid (CSF) cellular immune phenotype and activation contribute to 2-week and 1-year survival following CM. METHODS: We compared baseline CSF mononuclear cell phenotype and activation among adults with HIV-associated CM who died within 2 weeks of CM diagnosis to survivors who were alive at 1 year. The activated CSF T lymphocytes, CD14+ monocytes, and CD56+ natural killer cells were determined from freshly collected CSF using Cytek Aurora Spectroflo cytometry. Quantitative CSF soluble cryptococcal antigen (CrAg) titer from frozen CSF at baseline and 1 year was determined using CrAg lateral flow assay. Data were analyzed using STATA version 9. RESULTS: Compared to survivors, participants who died within 2 weeks had significantly lower absolute CSF CD8+ T cells at baseline. For every 10% increase in PD-1 expression at baseline, the relative risk of 2-week mortality increased by 20%-60%. CSF CD14+ monocytes among those who died demonstrated low HLA-DR+ and high CD163+ expression compared to survivors. We noted a significant reduction in the median CSF CrAg titer from 1:2560 at baseline to 1:5 at 1 year (P < .0001) with 8 of 21 (38%) participants testing negative for CSF CrAg. CONCLUSIONS: Expression of CD163 on CD14+ macrophages and immune exhaustion of CSF mononuclear cells at baseline are associated with an increased risk of early mortality in CM. After 1 year of treatment, approximately 4 in 10 patients with CM have a negative CSF CrAg.","journal":"The Journal of Infectious Diseases","year":2025,"id":572984,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":452980,"name":"Kenneth Ssebambulidde","orcid":"0000-0002-8125-0698","position":1,"is_corresponding":false},{"id":1139012,"name":"Samuel Okurut","orcid":"0000-0002-9292-8687","position":2,"is_corresponding":false},{"id":110706,"name":"Richard Kwizera","orcid":"0000-0002-5270-3539","position":3,"is_corresponding":false},{"id":526789,"name":"Martin Nabwana","orcid":"0000-0003-1727-9813","position":4,"is_corresponding":false},{"id":887950,"name":"Jane Gakuru","orcid":"0000-0003-0150-4887","position":5,"is_corresponding":false},{"id":919883,"name":"Jane Francis Ndyetukira","orcid":"0009-0007-3955-8107","position":6,"is_corresponding":false},{"id":1256956,"name":"Suzan Mulwana","orcid":null,"position":7,"is_corresponding":false},{"id":1479864,"name":"Lydia Nankungu","orcid":null,"position":8,"is_corresponding":false},{"id":1261793,"name":"Kizza Kandole Tadeo","orcid":null,"position":9,"is_corresponding":false},{"id":578702,"name":"Abdu K Musubire","orcid":"0000-0003-2410-5344","position":10,"is_corresponding":false},{"id":267658,"name":"David R. Boulware","orcid":"0000-0002-4715-0060","position":11,"is_corresponding":false},{"id":397657,"name":"David B. Meya","orcid":"0000-0002-8854-0321","position":12,"is_corresponding":false},{"id":644485,"name":"Morris K Rutakingirwa","orcid":"0000-0003-2276-360X","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40839770","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}