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

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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.

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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).

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Authors and Affiliations

  1. University of Minnesota, Minneapolis, MN, USA

    Mahsa Abassi, Bozena M. Morawski, David B. Meya & David R. Boulware

  2. Infectious Diseases Institute, PO BOX 22148, Mulago Hospital Complex, Kampala, Uganda

    Mahsa Abassi, Bozena M. Morawski, Noeline Nakasujja & David B. Meya

  3. Rakai Health Sciences Program, Entebbe, Uganda

    Gertrude Nakigozi

  4. Makerere University, Kampala, Uganda

    Noeline Nakasujja & David B. Meya

  5. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    **angrong Kong, Ronald Gray & Maria J. Wawer

  6. University of North Carolina, Chapel Hill, NC, USA

    Kevin Robertson

  7. Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ned Sacktor

Authors
  1. Mahsa Abassi
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  2. Bozena M. Morawski
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  3. Gertrude Nakigozi
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  4. Noeline Nakasujja
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  5. **angrong Kong
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  6. David B. Meya
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  7. Kevin Robertson
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  8. Ronald Gray
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  9. Maria J. Wawer
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  10. Ned Sacktor
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  11. David R. Boulware
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Corresponding author

Correspondence to Mahsa Abassi.

Ethics declarations

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.

Additional information

Ned Sacktor and David R. Boulware contributed equally to this work.

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Abassi, M., Morawski, B.M., Nakigozi, G. et al. Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda. J. Neurovirol. 23, 369–375 (2017). https://doi.org/10.1007/s13365-016-0505-9

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  • DOI: https://doi.org/10.1007/s13365-016-0505-9

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