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

Peluso, MJ; Valcour, V; Phanuphak, N; Ananworanich, J; Fletcher, JLK; Chalermchai, T; Krebs, SJ; ... Spudich, S; + view all (2017) Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. AIDS , 31 (2) pp. 247-252. 10.1097/QAD.0000000000001314. Green open access

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Abstract

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.

Type: Article
Title: Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAD.0000000000001314
Publisher version: http://dx.doi.org/10.1097/QAD.0000000000001314
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1538332
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