Objectives: The study aimed to assess and compare cerebrospinal fluid (CSF)-CXCL13 levels in People with HIV (PWH) with suspected neurosyphilis (NS), those with syphilis but without NS, and patients without treponema infection. Additionally, it aimed to evaluate changes in CSF-CXCL13 concentrations before and after antibiotic treatment., Design: This was a prospective cohort study involving 93 PWH suspected of NS. All participants underwent lumbar puncture, with CSF-CXCL13 levels measured at baseline and during follow-up in patients diagnosed with NS., Methods: CSF-CXCL13 levels were quantified using ELISA. The Mann-Whitney U test was used to analyze differences between groups, while the Wilcoxon test assessed within subject changes. ROC curve analysis determined the diagnostic efficacy of CSF-CXCL13 for NS., Results: Significantly higher CSF-CXCL13 levels were observed in patients with NS compared to those with syphilis without NS and non-syphilis patients. Posttreatment, a decline in CSF-CXCL13 levels was noted in all NS cases. A CSF-CXCL13 threshold exceeding 60.0 pg/ml, in conjunction with reactive CSF-FTA-ABS, yielded a sensitivity of 88.9% and a specificity of 97.6% for NS diagnosis., Conclusions: CSF-CXCL13 emerges as a valuable adjunctive biomarker for detecting NS in PWH, especially in cases with nonreactive CSF-VDRL. Monitoring CSF-CXCL13 levels also appears effective in evaluating therapeutic response in PWH undergoing NS treatment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)