Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

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Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

Gisslén, Magnus, 1962 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine

Keating, S. M. (author)

Spudich, S. (author)

Arechiga, V. (author)

Stephenson, S. (author)

Zetterberg, Henrik, 1973 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Di Germanio, C. (author)

Blennow, Kaj, 1958 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Fuchs, D. (author)

Hagberg, Lars, 1951 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine

Norris, P. J. (author)

Peterson, J. (author)

Shacklett, B. L. (author)

Yiannoutsos, C. T. (author)

Price, R. W. (author)

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2021-05-13
2021
English.
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5

Related links:: https://journals.plo...; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Objective To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control. Methods This is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with >= 1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau. Findings HIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200-350 blood CD4+ T cells/mu L and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.

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By the author/editor: Gisslén, Magnus, ...; Keating, S. M.; Spudich, S.; Arechiga, V.; Stephenson, S.; Zetterberg, Henr ...; show more...; Di Germanio, C.; Blennow, Kaj, 19 ...; Fuchs, D.; Hagberg, Lars, 1 ...; Norris, P. J.; Peterson, J.; Shacklett, B. L.; Yiannoutsos, C. ...; Price, R. W.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

Articles in the publication: PLoS ONE

By the university: University of Gothenburg

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Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

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