Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection
MJ Peluso, V Valcour, N Phanuphak, J Ananworanich… - Aids, 2017 - journals.lww.com
Aids, 2017•journals.lww.com
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 …
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 …
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.
Background
Even in the age of widely available combination antiretroviral therapy (cART), the burden of neurologic disease in HIV-infected patients is significant and persistent [1, 2]. Investigations into the neuropathogenesis of HIV-1 in the central nervous system (CNS) demonstrate viral penetration into the cerebrospinal fluid (CSF) during acute infection [3], suggesting the virus could affect long-term neurologic outcomes from early timepoints.
Lippincott Williams & Wilkins