Cerebrospinal fluid CXCL13 identifies a subgroup of people living with HIV with prominent intrathecal synthesis, immune activation, and neurocognitive impairment regardless of effective antiretroviral therapy

BackgroundPlasma C-X-C-motif chemokine ligand-13 (CXCL13) has been linked to disease progression and mortality in people living with HIV (PLWH) and is a candidate target for immune-based strategies for HIV cure. Its role in central nervous system (CNS) of PLWH has not been detailed. We described CSF CXCL13 levels and its potential associations with neurological outcomes. MethodsCross-sectional study enrolling PLWH without confounding for CXCL13 production. Subjects were divided according to CSF HIV-RNA in controllers (<20 cp/mL) and viremics. CSF CXCL13, and biomarkers of blood-brain barrier (BBB) impairment, intrathecal synthesis, and immune activation were measured by commercial immunoturbidimetric and ELISA assays. All subjects underwent neurocognitive assessment. Sensitivity analyses were conducted in subjects with intact BBB only. Results175 subjects were included. Prevalence of detectable CSF CXCL13 was higher in viremics (31.4%) compared to controllers (13.5%; OR 2.9 [1.4-6.3], p=0.006), but median CSF levels did not change (15.8 [8.2-91.0] vs 10.0 [8.1-14.2] pg/mL). In viremics (n=86), CXCL13 associated with higher CSF HIV-RNA, proteins, neopterin, Tourtelotte index, and CSF-to-serum albumin ratio. In controllers (n=89), CXCL13 associated with higher CD4+T-cells count, CD4/CD8 ratio, CSF proteins, neopterin, and several intrathecal synthesis markers. Detection of CSF CXCL13 in controllers increased the likelihood of HIV-associated neurocognitive disorders (58.3% vs 28.6%, p=0.041) and HIV-related CNS disorders (8.3% vs 0%, p=0.011). Sensitivity analyses confirmed all these findings. ConclusionsCSF CXCL13 identified a subgroup of PLWH presenting increased CNS IgG synthesis, and immune activation. In controllers, CSF CXCL13 associated with increased likelihood of neurocognitive impairment and HIV-related CNS disorders. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC="FIGDIR/small/22283427v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@bfe68aorg.highwire.dtl.DTLVardef@b87cc4org.highwire.dtl.DTLVardef@766cdorg.highwire.dtl.DTLVardef@1ee510f_HPS_FORMAT_FIGEXP M_FIG C_FIG