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

Deanna Saylor, Anupama Kumar, Gertrude Nakigozi, Aggrey Anok, James Batte, Alice Kisakye, Richard Mayanja, Noeline Nakasujja, Kevin R. Robertson, Ronald H. Gray, Maria J. Wawer, Carlos A. Pardo, Ned Sacktor

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)735-740
Number of pages6
JournalJournal of neurovirology
Volume25
Issue number6
DOIs
StatePublished - Dec 1 2019

Keywords

  • All-cause mortality
  • Depression
  • HIV
  • HIV-associated neurocognitive disorder
  • Interleukin-6
  • Uganda

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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