['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.', 'Cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints.', 'AHI (n\u200a=\u200a33) and CHI (n\u200a=\u200a34) 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\u200a=\u200a24], 1 year in CHI participants [n\u200a=\u200a10]). Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations.', 'Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/L; p\u200a=\u200a0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130\u200ang/L; p\u200a=\u200a0.003). In untreated CHI, YKL-40 correlated with neopterin (r\u200a=\u200a0.51, p\u200a=\u200a0.0025), chemokine (CXC-motif) ligand-10 (r\u200a=\u200a0.44, p\u200a=\u200a0.011), and neurofilament light chain (r\u200a=\u200a0.56, p\u200a=\u200a0.0008) in CSF.'] Is immediate initiation of cART associated with lower levels of cerebrospinal fluid YKL-40 , a marker of microglial activation , in HIV-1 infection?