Interleukin-6 is associated with mortality and neuropsychiatric outcomes in antiretroviral-naïve adults in Rakai, Uganda
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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.
KeywordsHIV-associated neurocognitive disorder HIV Interleukin-6 Uganda Depression All-cause mortality
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.
Compliance with ethical standards
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.
Conflict of interest
The authors declare that they have no conflict of interest.
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