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Interleukin-6 is associated with mortality and neuropsychiatric outcomes in antiretroviral-naïve adults in Rakai, Uganda

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Abstract

Serum interleukin-6 (IL-6) and D-dimer have been associated with multiple adverse outcomes in HIV-infected (HIV+) individuals, but their association with neuropsychiatric outcomes, including HIV-associated neurocognitive disorder (HAND) and depression, headaches, and peripheral neuropathy have not been investigated. Three hundred ninety-nine HIV+ antiretroviral therapy (ART)-naïve adults in Rakai, Uganda, were enrolled in a longitudinal cohort study and completed a neurological evaluation, neurocognitive assessment, and venous blood draw. Half of the participants had advanced immunosuppression (CD4 count < 200 cells/μL), and half had moderate immunosuppression (CD4 count 350–500 cells/μL). All-cause mortality was determined by verbal autopsy within 2 years. HAND was determined using Frascati criteria, and depression was defined by the Center for Epidemiologic Studies-Depression (CES-D) scale. Neuropathy was defined as the presence of > 1 neuropathy symptom and > 1 neuropathy sign. Headaches were identified by self-report. Serum D-dimer levels were determined using ELISA and IL-6 levels using singleplex assays. Participants were 53% male, mean age 35 + 8 years, and mean education 5 + 3 years. Participants with advanced immunosuppression had significantly higher levels of IL-6 (p < 0.001) and a trend toward higher D-dimer levels (p = 0.06). IL-6 was higher among participants with HAND (p = 0.01), with depression (p = 0.03) and among those who died within 2 years (p = 0.001) but not those with neuropathy or headaches. D-dimer did not vary significantly by any outcome. Systemic inflammation as measured by serum IL-6 is associated with an increased risk of advanced immunosuppression, all-cause mortality, HAND, and depression but not neuropathy or headaches among ART-naïve HIV+ adults in rural Uganda.

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Acknowledgments

The authors would like to thank the study participants and staff at the Rakai Health Sciences Program for the time and effort they dedicated to this study.

Sources of support

This study was supported by the National Institutes of Health (MH099733, MH075673, MH080661-08, L30NS088658, NS065729-05S2, P30AI094189-01A1) with additional funding from the Johns Hopkins Center for Global Health.

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Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, Meyer 6-113, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    Deanna Saylor, Anupama Kumar, Carlos A. Pardo & Ned Sacktor

  2. Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia

    Deanna Saylor

  3. Rakai Health Sciences Program, Kalisizo, Uganda

    Gertrude Nakigozi, Aggrey Anok, James Batte, Alice Kisakye & Richard Mayanja

  4. Department of Psychiatry, Makerere University, Kampala, Uganda

    Noeline Nakasujja

  5. Department of Neurology, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA

    Kevin R. Robertson

  6. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Ronald H. Gray & Maria J. Wawer

Authors
  1. Deanna Saylor
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  2. Anupama Kumar
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  3. Gertrude Nakigozi
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  4. Aggrey Anok
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  6. Alice Kisakye
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  7. Richard Mayanja
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  8. Noeline Nakasujja
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  9. Kevin R. Robertson
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  10. Ronald H. Gray
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  12. Carlos A. Pardo
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  13. Ned Sacktor
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Corresponding author

Correspondence to Deanna Saylor.

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Written informed consent was obtained from all participants. This study was approved by the Western Institutional Review Board, the Uganda Virus Research Institute Research and Ethics Committee, and the Uganda National Council for Science and Technology.

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The authors declare that they have no conflict of interest.

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Saylor, D., Kumar, A., Nakigozi, G. et al. Interleukin-6 is associated with mortality and neuropsychiatric outcomes in antiretroviral-naïve adults in Rakai, Uganda. J. Neurovirol. 25, 735–740 (2019). https://doi.org/10.1007/s13365-019-00759-6

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  • DOI: https://doi.org/10.1007/s13365-019-00759-6

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