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01-04-2016

Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection

Authors: Josué Pérez-Santiago, Rachel D. Schrier, Michelli F. de Oliveira, Sara Gianella, Susanna R. Var, Tyler R. C. Day, Miguel Ramirez-Gaona, Jesse D. Suben, Ben Murrell, Marta Massanella, Mariana Cherner, Davey M. Smith, Ronald J. Ellis, Scott L. Letendre, Sanjay R. Mehta

Published in: Journal of NeuroVirology | Issue 2/2016

Abstract

Cell-free mitochondiral DNA (mtDNA) is an immunogenic molecule associated with many inflammatory conditions. We evaluated the relationship between cell-free mtDNA in cerebrospinal fluid (CSF) and neurocognitive performance and inflammation during HIV infection. In a cross-sectional analysis, we evaluated the association of mtDNA levels with clinical assessments, inflammatory markers, and neurocognitive performance in 28 HIV-infected individuals. In CSF, we measured mtDNA levels by droplet digital PCR, and soluble CD14 and CD163, neurofilament light, and neopterin by ELISA. In blood and CSF, we measured soluble IP-10, MCP-1, TNF-α, and IL-6 by ELISA, and intracellular expression of IL-2, IFN-γ, and TNF-α in CD4⁺ and CD8⁺ T cells by flow cytometry. We also evaluated the relationship between CSF pleocytosis and mtDNA longitudinally in another set of five individuals participating in an antiretroviral treatment (ART) interruption study. Cell-free CSF mtDNA levels strongly correlated with neurocognitive performance among individuals with neurocognitive impairment (NCI) (r = 0.77, p = 0.001). CSF mtDNA also correlated with levels of IP-10 in CSF (r = 0.70, p = 0.007) and MCP-1 in blood plasma (r = 0.66, p = 0.01) in individuals with NCI. There were no significant associations between inflammatory markers and mtDNA in subjects without NCI, and levels of mtDNA did not differ between subjects with and without NCI. MtDNA levels preceded pleocytosis and HIV RNA following ART interruption. Cell-free mtDNA in CSF was strongly associated with the severity of neurocognitive dysfunction and inflammation only in individuals with NCI. Our findings suggest that within a subset of subjects cell-free CSF mtDNA is associated with inflammation and degree of NCI.

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Title: Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection
Authors: Josué Pérez-Santiago
Rachel D. Schrier
Michelli F. de Oliveira
Sara Gianella
Susanna R. Var
Tyler R. C. Day
Miguel Ramirez-Gaona
Jesse D. Suben
Ben Murrell
Marta Massanella
Mariana Cherner
Davey M. Smith
Ronald J. Ellis
Scott L. Letendre
Sanjay R. Mehta
Publication date: 01-04-2016
Publisher: Springer US
Published in: Journal of NeuroVirology / Issue 2/2016
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-015-0384-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cell-free mitochondrial DNA in CSF is associated with early viral rebound, inflammation, and severity of neurocognitive deficits in HIV infection

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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