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

AIDS. 2017 Jan 14;31(2):247-252. doi: 10.1097/QAD.0000000000001314.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Cerebrospinal Fluid / chemistry*
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid*
  • Cross-Sectional Studies
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Neurocognitive Disorders / pathology*
  • Secondary Prevention*
  • Young Adult


  • Anti-Retroviral Agents
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1