title: Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury in HIV.
abstract: OBJECTIVE
  Although blood-brain barrier (BBB) impairment has been reported in HIV-infected individuals, characterization of this impairment has not been clearly defined.
  
  
  METHODS
  BBB integrity was measured by CSF/plasma albumin ratio in this cross-sectional study of 631 HIV-infected individuals and 71 controls. We also analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and neurofilament light chain protein (NFL) concentrations. The HIV-infected participants included untreated neuroasymptomatic patients, patients with untreated HIV-associated dementia (HAD), and participants on suppressive antiretroviral treatment (ART).
  
  
  RESULTS
  The albumin ratio was significantly increased in patients with HAD compared to all other groups. There were no significant differences between untreated neuroasymptomatic participants, treated participants, and controls. BBB integrity, however, correlated significantly with CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated neuroasymptomatic participants. In a multiple linear regression analysis, age, CSF neopterin, and CSF leukocyte count stood out as independent predictors of albumin ratio. A significant correlation was found between albumin ratio and CSF NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin ratio, age, and CD4 cell count were confirmed as independent predictors of CSF NFL in multivariable analysis.
  
  
  CONCLUSIONS
  BBB disruption was mainly found in patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin ratios also correlated with CSF inflammatory markers and NFL in untreated neuroasymptomatic participants. These findings give support to the association among BBB deterioration, intrathecal immunoactivation, and neuronal injury in untreated neuroasymptomatic HIV-infected individuals.
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Anesten
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Aylin
authors.initials: A
authors.lastname: Yilmaz
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine (B.A., A.Y., L.H., M.G.), and Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology (H.Z.), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg, Sweden; Departments of Neurology and HIV Medicine (B.J.B.), St Vincent's Hospital and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia; Division of Biological Chemistry (D.F.), Biocenter, Innsbruck Medical University, Innsbruck, Austria; and Department of Neurology (R.W.P.), University of California San Francisco.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén