Association between cerebrospinal fluid CXCL10 and neurocognitive disorders in people living with HIV: a meta-analysis.

BACKGROUND: C-X-C motif chemokine ligand 10 (CXCL10) is implicated in HIV-associated neuroinflammation, yet its association with HIV-associated neurocognitive disorders (HAND) remains unclear. We conducted a meta-analysis to evaluate cerebrospinal fluid (CSF) CXCL10 differences between people living with HIV (PLWH) with and without HAND and to assess the odds of HAND in relation to high versus low CSF CXCL10 levels. METHODS: PubMed, Embase, and Web of Science were systematically searched. Observational studies reporting CSF CXCL10 levels in adult PLWH with and without HAND were included. Standardized mean difference (SMD) and odds ratio (OR) were pooled using random-effects models accounting for the potential influence of heterogeneity. RESULTS: Eleven studies involving 1,536 PLWH were included. Compared to those without HAND, PLWH with HAND had significantly higher CSF CXCL10 levels (SMD: 0.56, 95% CI: 0.17-0.96; p < 0.001), with high heterogeneity (I² = 86% and τ² = 0.31). The 95% prediction interval (PI: - 0.78 to 1.91) indicated substantial between-study variability. Subgroup analyses showed significantly greater CXCL10 elevation in studies with ≤ 50% ART coverage (SMD: 0.90 vs. 0.17; p = 0.04) and in those evaluating HIV-associated dementia (SMD: 1.45 vs. 0.37; p < 0.001). Meta-regression did not identify any statistically significant moderators, although ART proportion and CD4 + count explained 29.2% and 25.6% of the variance, respectively. No significant association was found between high CSF CXCL10 and HAND (OR: 1.41, 95% CI: 0.90-2.22; p = 0.13). CONCLUSION: Elevated CSF CXCL10 may be associated with HAND in PLWH, particularly among ART-naïve individuals and in more severe cognitive impairment. However, substantial heterogeneity and a wide PI suggest that the strength of this association varies across populations. CSF CXCL10 remains a promising but not definitive biomarker for HAND risk stratification.