CSF CXCL13 as a longitudinal marker for neurocognition in HIV-1-associated dementia after start of treatment in cART-naïve patients

Jürgen Panholzer , Anna R. Tröscher , Vincent Böhm , Raimund Helbok , Christian Eggers ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-7748397/v1

Objectives Despite suppression of viral replication by antiretroviral therapy (cART) HIV-associated neurocognitive disorders (HAND) may persist. This involves chronic inflammation with activation of the monocyte-macrophage-microglia axis. We examined CXCL13, a chemokine released by these cells, as a possible marker for HAND treatment response. Methods We longitudinally analyzed cerebrospinal fluid (CSF) from before and during newly initiated cART of people living with HIV (PLWH) with HIV-associated dementia (HAD). CXCL13_CSF was determined by ELISA. We studied the correlation of CXCL13_CSF with HAD as measured by the Memorial Sloan Kettering score (MSK-score) and with CSF and blood parameters. Results Twelve treatment-naïve patients with HAD were included. Prior to cART the correlation of CXCL13_CSF (τ_b = .575, p = 0.051) with MSK-score narrowly missed significance. At an average of 2,9 months after start of cART, CXCL13_CSF strongly correlated with MSK-score (τ_b = .746, p = 0.005). Also, the magnitude of the longitudinal change of CXCL-13_CSF correlated with the change of MSK-score (τ_b = .460, p = 0.048). No correlation was found between MSK-score and CSF white blood cell count (WBC_CSF) as well as HIV-RNA (plasma, CSF). Conclusions CXCL13_CSF showed a significant correlation with HAD but not with WBC_CSF and HIV-RNA. As CXCL13 in the CNS is secreted by macrophages and microglia our results suggest a significant role of the monocyte-macrophage-microglia axis as a line of immunological defense relatively independent of viral replication. If supported by further studies CXCL13 might serve as CSF biomarker in HIV patients with HAD.