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J Neurovirol. 2020 Mar 19. doi: 10.1007/s13365-020-00834-3. [Epub ahead of print]

Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV.

Author information

1
Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
2
Department of Biostatistics, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA.
3
Department of Gynecology Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
4
Department of Pharmacology and Neuroscience, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
5
Medical Innovation Collaborative of North Texas, Irving, TX, USA.
6
Department of Microbiology, Immunology and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA. Kathleen.Borgmann@unthsc.edu.
7
Department of Pharmacology and Neuroscience, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA. Kathleen.Borgmann@unthsc.edu.

Abstract

Inflammation in people living with HIV (PLWH) correlates with severity of HIV-associated neurocognitive disorders. The objective of this study is to identify blood-based markers of neurocognitive function in a demographic balanced cohort of PLWH. Seven neurocognitive domains were evaluated in 121 seropositive Black/African American, Non-Hispanic White, and White Hispanic men and women using computerized assessments. Associations among standardized neurocognitive function and HIV-related parameters, relevant sociodemographic variables, and inflammation-associated cytokines measured in plasma and cellular supernatants were examined using multivariate and univariate regression models. Outlier and covariate analyses were used to identify and normalize for education level, CD4 T cell count, viral load, CNS and drug abuse comorbidities, which could influence biomarker and neurocognitive function associations. Plasma levels of chemokine (C-C motif) ligand (CCL) 8 significantly associated with memory, complex attention, cognitive flexibility, psychomotor speed, executive function, and processing speed. Plasma tissue inhibitor of metalloproteinases 1 associated with the aforementioned domains except memory and processing speed. In addition, plasma interleukin-23 significantly associated with processing speed and executive function. Analysis of peripheral blood cell culture supernatants revealed no significant markers for neurocognitive function. In this cohort, CD4 T cell count and education level also significantly associated with neurocognitive function. All identified inflammatory biomarkers demonstrated a negative correlation to neurocognitive function. These cytokines have known connections to HIV pathophysiology and are potential biomarkers for neurocognitive function in PLWH with promising clinical applications.

KEYWORDS:

CNS; Chronic immune activation; HIV-associated neurocognitive disorders (HAND); Health disparities

PMID:
32193795
DOI:
10.1007/s13365-020-00834-3

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