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Cytokine. 2016 Jul;83:139-146. doi: 10.1016/j.cyto.2016.04.004. Epub 2016 Apr 28.

CSF/plasma HIV-1 RNA discordance even at low levels is associated with up-regulation of host inflammatory mediators in CSF.

Author information

1
Institute of Infection and Global Health, University of Liverpool, UK; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK; Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK. Electronic address: s.nightingale@liv.ac.uk.
2
Institute of Infection and Global Health, University of Liverpool, UK; Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
3
Brighton and Sussex University Hospitals NHS Trust, UK.
4
St Marys' Hospital, Imperial College Heathcare NHS Trust, London, UK.
5
St Stephen's AIDS Research Trust and Chelsea and Westminster Hospital NHS Foundation Trust, UK.
6
Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, UK.
7
North Manchester General Hospital, Pennine Acute Hospitals NHS Trust, UK.
8
North Middlesex University Hospital NHS Trust, UK.
9
Research Department of Infection and Population Health, University College London, UK.
10
Victoria Royal Infirmary, Newcastle upon Tyne Hospitals NHS Trust, UK.
11
Royal Infirmary of Edinburgh, NHS Lothian, UK.
12
Leeds General Infirmary, Leeds Teaching Hosptials NHS Trust, UK.
13
Kings College Hospital NHS Foundation Trust, London, UK.
14
Institute of Infection and Global Health, University of Liverpool, UK.
15
Vaccine Evaluation Unit at the Health Protection Agency (HPA) North West, Manchester, UK.
16
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.

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 non-discordant 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.

KEYWORDS:

CSF escape; Cerebrospinal fluid; HIV; Inflammation; Sanctuary site

PMID:
27131579
PMCID:
PMC4889775
DOI:
10.1016/j.cyto.2016.04.004
[Indexed for MEDLINE]
Free PMC Article

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