Cerebrospinal Fluid Mononuclear Cell Phenotype and Activation Predictors of 2-Week and 1-Year Survival Among Persons With HIV-Associated Cryptococcal Meningitis

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.