Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

Objective: To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. Design: A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. Methods: AHI (n=33) and CHI (n=34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow-up on cART in a subset of these individuals [6 months in AHI participants (n=24), 1 year in CHI participants (n-10)]. Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Results: Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/ l; P=0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/l; P=0.003). In untreated CHI, YKL-40 correlated with neopterin (r=0.51, P=0.0025), chemokine (CXC-motif) ligand-10 (r=0.44, P=0.011), and neurofilament light chain (r=0.56, P=0.0008) in CSF. Conclusions: This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.