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Journal of NeuroVirology

, Volume 23, Issue 3, pp 369–375 | Cite as

Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda

  • Mahsa AbassiEmail author
  • Bozena M. Morawski
  • Gertrude Nakigozi
  • Noeline Nakasujja
  • Xiangrong Kong
  • David B. Meya
  • Kevin Robertson
  • Ronald Gray
  • Maria J. Wawer
  • Ned Sacktor
  • David R. Boulware
Article

Abstract

In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/μL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid β42. Individuals with CD4 351–500 cells/μL (N = 40) had significantly higher CSF levels of interleukin (IL)-1β, amyloid β42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.

Keywords

HIV-associated neurocognitive disorders Cytokine expression Neurodegenerative biomarkers Inflammation Dementia 

Notes

Acknowledgements

The authors thank the support from the National Institutes of Health and Fogarty International Center (R01MH099733, R01NS086312, T32AI055433, U01AI089244, and R25TW009345; R01AI110324; U01AI10031) and the Bill and Melinda Gates Foundation (22006).

Compliance with ethical standards

The study, including the optional lumbar puncture, was reviewed and approved by institutional review boards in Uganda (Research and Ethics Committee, Uganda Virus Research Institute; Uganda National Council for Science and Technology) and in the USA (Western Institutional Review Board, Johns Hopkins University).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

13365_2016_505_MOESM1_ESM.docx (42 kb)
Supplemental Table 1 (DOCX 42 kb)
13365_2016_505_MOESM2_ESM.docx (44 kb)
Supplemental Table 2 (DOCX 44 kb)
13365_2016_505_MOESM3_ESM.docx (45 kb)
Supplemental Table 3 (DOCX 45 kb)

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Copyright information

© Journal of NeuroVirology, Inc. 2016

Authors and Affiliations

  • Mahsa Abassi
    • 1
    • 2
    Email author
  • Bozena M. Morawski
    • 1
    • 2
  • Gertrude Nakigozi
    • 3
  • Noeline Nakasujja
    • 2
    • 4
  • Xiangrong Kong
    • 5
  • David B. Meya
    • 1
    • 2
    • 4
  • Kevin Robertson
    • 6
  • Ronald Gray
    • 5
  • Maria J. Wawer
    • 5
  • Ned Sacktor
    • 7
  • David R. Boulware
    • 1
  1. 1.University of MinnesotaMinneapolisUSA
  2. 2.Infectious Diseases InstituteKampalaUganda
  3. 3.Rakai Health Sciences ProgramEntebbeUganda
  4. 4.Makerere UniversityKampalaUganda
  5. 5.Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  6. 6.University of North CarolinaChapel HillUSA
  7. 7.Johns Hopkins University School of MedicineBaltimoreUSA

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