title: Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.
abstract: BACKGROUND
  Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.
  
  
  METHODS
  With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation.
  
  
  RESULTS
  While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups.
  
  
  CONCLUSIONS
  Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.
authors: Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
authors: Jan
authors: J
authors: Jessen Krut
authors: Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
authors: Tomas
authors: T
authors: Mellberg
authors: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors: Richard W
authors: RW
authors: Price
authors: Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
authors: Lars
authors: L
authors: Hagberg
authors: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors: Dietmar
authors: D
authors: Fuchs
authors: Institute of Neuroscience and Physiology, Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Lars
authors: L
authors: Rosengren
authors: Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors: Staffan
authors: S
authors: Nilsson
authors: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden ; UCL Institute of Neurology, Queen Square, London, United Kingdom.
authors: Henrik
authors: H
authors: Zetterberg
authors: Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
authors: Magnus
authors: M
authors: Gisslén
mesh_terms: D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid*; D000328:Adult; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications*; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000150:complications*; D015497:HIV-1; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009474:Neurons / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D019798:Neopterin