Cerebrospinal Fluid Transcriptional Immune Pathways Linked to Survival in HIV-Associated Tuberculous Meningitis

BACKGROUND: TB meningitis (TBM) has up to 50% mortality in people living with HIV. We investigated differences in cerebrospinal fluid (CSF) host immune responses associated with short-term mortality. METHODS: We enrolled a prospective cohort of adults with definite, probable and possible HIV-related TBM in Kampala, Uganda. Metagenomic next-generation sequencing (mNGS) of bulk CSF RNA was used to detect co-infecting or alternate CNS pathogens and refine cohort diagnosis. Host transcriptomic profiles from the refined cohort were then compared between 14-day survivors and non-survivors. RESULTS: CSF mNGS reclassified or excluded 14% of participants based on pathogen detection, yielding 110 participants for transcriptomic analysis, of whom 23% (n=25) died within 14 days. More than 2000 genes were differentially expressed in the CSF based on 14-day mortality (adjusted p-value