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



A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints.



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.



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.



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.
aDepartment of Medicine, Brigham and Women's Hospital, Boston, Massachusetts bDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA cSEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand dUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring eHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland , USA fDepartment of Infectious Diseases, Institute of Biomedicine, Gothenburg gDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden hUniversity College London Institute of Neurology, London, UK iYale University School of Medicine, New Haven, Connecticut, USA.
Michael J
MJ
Peluso
Victor
V
Valcour
Nittaya
N
Phanuphak
Jintanat
J
Ananworanich
James L K
JL
Fletcher
Thep
T
Chalermchai
Shelly J
SJ
Krebs
Merlin L
ML
Robb
Joanna
J
Hellmuth
Magnus
M
Gisslén
Henrik
H
Zetterberg
Serena
S
Spudich
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D019965:Neurocognitive Disorders / Q000473:pathology*; D055502:Secondary Prevention; D055815:Young Adult
D044966:Anti-Retroviral Agents; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1