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 cryptococcal meningitis 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 v9. Results Compared to survivors, participants who died within 2 weeks had significantly low 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 <0.0001) with 8/21 (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 one year of treatment, approximately 4 in 10 patients with CM have a negative CSF CrAg.