10.7272/Q61R6NRZ
Price, Richard
0000-0001-5429-6044
University of California, San Francisco
Gisslen, Magnus
University of Gothenburg
Keating, Sheila
Vitalant
Spudich, Serena
Yale University
Arechiga, Victor
University of California, San Francisco
Stephenson, Sophie
University of California, San Francisco
Zetterberg, Henrik
University of Gothenburg
Di Germanio, Clara
Vitalant
Blennow, Kaj
University of Gothenburg
Hagberg, Lars
University of Gothenburg
Norris, Philip
0000-0003-0526-2088
Vitalant
Peterson, Julia
University of California, San Francisco
Shacklett, Barbara
0000-0002-7067-732X
University of California, Davis
Yiannoutsos, Constantin
Indiana University
Compartmentalization of cerebrospinal fluid inflammation across the
spectrum of HIV infection
Dryad
dataset
2021
FOS: Medical and health sciences
National Institute of Neurological Disorders and Stroke
https://ror.org/01s5ya894
R01 NS094067 and R01 NS094067-05S1
National Institute of Mental Health
https://ror.org/04xeg9z08
R21 MH096619
National Institute of Mental Health
https://ror.org/04xeg9z08
P01 MH094177
National Institute of Mental Health
https://ror.org/04xeg9z08
R01 MH081772
2021-04-09T00:00:00Z
2021-04-09T00:00:00Z
en
74602 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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/µL 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.
CSF was collected by lumbar puncture and plsama/serum by phlebotomy. CSF
was placed immediately on wet ice and subsequently subjected to low-speed
centrifugation to remove cells, aliquoted and stored within 2 hours of
collection at <-70°C until the time of HIV-1 RNA and biomarker
assays. Blood was collected either in EDTA or as serum, aliquoted and
stored in parallel with CSF for later batch assays. Details are outlined
in the manuscript derived from this data.
This dataset details the results of inflammatory biomarker measurements
and background biomarkers in CSF and blood in a spectrum of HIV-infected
individuals along with uninfected controls. The samples were selected from
archived samples collected in San Francisco and Gothenburg as detailed in
the parent manuscript.