CSF/plasma HIV-1 RNA discordance even at low levels is associated with up-regulation of host inflammatory mediators in CSF
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Introduction: HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed
CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree
of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines,
chemokines and associated mediators were raised in patients with CSF/plasma discordance at different
levels.
Methods: A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric
bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples
matched for plasma HIV-1 RNA. Discordant samples were subdivided into ‘high discordance’ (>1log10)
and ‘low discordance’ (0.5–1log10, or ultrasensitive discordance). CSF mediators significant in univariate
analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative
mediator concentrations.
Results: In univariate analysis 19 of 21 CSF mediators were significantly higher in discordant than nondiscordant
samples. There were no significant differences between samples with high versus low discordance.
The samples grouped into two clusters which corresponded to CSF/plasma discordance
(p < 0.0001). In cluster one all mediators had relatively high abundance; this included 18 discordant samples
and three non-discordant samples. In cluster two all mediators had relatively low abundance; this
included 18 non-discordant samples and one non-discordant sample with ultrasensitive discordance only.
Conclusions: CSF/plasma discordance is associated with potentially damaging neuroinflammatory process.
Patients with discordance at lower levels (ie. 0.5–1log10) should also be investigated as mediator profiles
were similar to those with discordance >1log10. Sensitive testing may have a role to determine whether
ultrasensitive discordance is present in those with low level CSF escape.
CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree
of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines,
chemokines and associated mediators were raised in patients with CSF/plasma discordance at different
levels.
Methods: A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric
bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples
matched for plasma HIV-1 RNA. Discordant samples were subdivided into ‘high discordance’ (>1log10)
and ‘low discordance’ (0.5–1log10, or ultrasensitive discordance). CSF mediators significant in univariate
analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative
mediator concentrations.
Results: In univariate analysis 19 of 21 CSF mediators were significantly higher in discordant than nondiscordant
samples. There were no significant differences between samples with high versus low discordance.
The samples grouped into two clusters which corresponded to CSF/plasma discordance
(p < 0.0001). In cluster one all mediators had relatively high abundance; this included 18 discordant samples
and three non-discordant samples. In cluster two all mediators had relatively low abundance; this
included 18 non-discordant samples and one non-discordant sample with ultrasensitive discordance only.
Conclusions: CSF/plasma discordance is associated with potentially damaging neuroinflammatory process.
Patients with discordance at lower levels (ie. 0.5–1log10) should also be investigated as mediator profiles
were similar to those with discordance >1log10. Sensitive testing may have a role to determine whether
ultrasensitive discordance is present in those with low level CSF escape.
Date Issued
2016-04-28
Date Acceptance
2016-04-05
Citation
Cytokine, 2016, 83, pp.139-146
ISSN
1096-0023
Publisher
Elsevier
Start Page
139
End Page
146
Journal / Book Title
Cytokine
Volume
83
Copyright Statement
Creative Commons Attribution 4.0 International (CC BY 4.0)
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Immunology
HIV
Cerebrospinal fluid
CSF escape
Sanctuary site
Inflammation
IMMUNODEFICIENCY-VIRUS INFECTION
CENTRAL-NERVOUS-SYSTEM
CEREBROSPINAL-FLUID
NEUROCOGNITIVE DISORDERS
ANTIRETROVIRAL THERAPY
IMPAIRMENT
BIOMARKERS
MARKERS
PLASMA
ERA
Publication Status
Published