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

Nightingale, S, Michael, BD ORCID: 0000-0002-8693-8926, Fisher, M, Winston, A, Nelson, M, Taylor, S, Ustianowski, A, Ainsworth, J, Gilson, R, Haddow, L
et al (show 10 more authors) (2016) CSF/plasma HIV-1 RNA discordance even at low levels is associated with up-regulation of host inflammatory mediators in CSF. Cytokine, 83. pp. 139-146.

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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.

Item Type: Article
Uncontrolled Keywords: HIV, Cerebrospinal fluid, CSF escape, Sanctuary site, Inflammation
Depositing User: Symplectic Admin
Date Deposited: 17 Aug 2018 14:24
Last Modified: 19 Jan 2023 01:28
DOI: 10.1016/j.cyto.2016.04.004
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3025152

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