Pragney Deme1, Mohammed Moniruzzaman1, David Moore1, Robert Heaton1, Ronald Ellis1, Scott Letendre1, Norman Haughey2. 1. From the Department of Neurology (P.D., M.M., N.H.), Johns Hopkins University School of Medicine, Baltimore, MD; HIV Neurobehavioral Research Program and Departments of Neurosciences and Psychiatry (D.M., R.H., R.E., S.L.), School of Medicine, University of California, San Diego, La Jolla; and the Department of Psychiatry (N.H.), Johns Hopkins University School of Medicine, Baltimore, MD. 2. From the Department of Neurology (P.D., M.M., N.H.), Johns Hopkins University School of Medicine, Baltimore, MD; HIV Neurobehavioral Research Program and Departments of Neurosciences and Psychiatry (D.M., R.H., R.E., S.L.), School of Medicine, University of California, San Diego, La Jolla; and the Department of Psychiatry (N.H.), Johns Hopkins University School of Medicine, Baltimore, MD. nhaughe1@jhmi.edu.
Abstract
BACKGROUND AND OBJECTIVES: To determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with HIV (PWH). METHODS: We measured 42 eicosanoids in a longitudinal study of 95 PWH and 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers, and a neuropsychological test battery assessing 7 cognitive domains were administered to all participants at 2 study visits over an average of 6.5 months. RESULTS: Plasma eicosanoid concentrations were elevated in PWH (n = 95) compared with seronegative controls (n = 25) (100% prediction power at 5% false discovery rate [FDR], α = 0.0531) and were negatively associated with lower current and nadir CD4 lymphocyte counts. Higher levels of eicosanoids were associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated proinflammatory eicosanoids (24% prediction power at 5% FDR and 42.4% prediction power at 10% FDR, α = 0.10). Longitudinal analyses showed that eicosanoid levels were correlated with viral load and with plasma creatinine. Despite associations of eicosanoids with viral loads, elevated plasma eicosanoids were similar in virally suppressed and not fully suppressed PWH. DISCUSSION: These data show that HIV infection is associated with a robust production of eicosanoids that are not substantially reduced by antiretroviral therapy (ART). The sustained elevation of these oxylipins in PWH despite ART may contribute to an accelerated aging phenotype that includes earlier than expected brain and peripheral organ damage.
BACKGROUND AND OBJECTIVES: To determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with HIV (PWH). METHODS: We measured 42 eicosanoids in a longitudinal study of 95 PWH and 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers, and a neuropsychological test battery assessing 7 cognitive domains were administered to all participants at 2 study visits over an average of 6.5 months. RESULTS: Plasma eicosanoid concentrations were elevated in PWH (n = 95) compared with seronegative controls (n = 25) (100% prediction power at 5% false discovery rate [FDR], α = 0.0531) and were negatively associated with lower current and nadir CD4 lymphocyte counts. Higher levels of eicosanoids were associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated proinflammatory eicosanoids (24% prediction power at 5% FDR and 42.4% prediction power at 10% FDR, α = 0.10). Longitudinal analyses showed that eicosanoid levels were correlated with viral load and with plasma creatinine. Despite associations of eicosanoids with viral loads, elevated plasma eicosanoids were similar in virally suppressed and not fully suppressed PWH. DISCUSSION: These data show that HIV infection is associated with a robust production of eicosanoids that are not substantially reduced by antiretroviral therapy (ART). The sustained elevation of these oxylipins in PWH despite ART may contribute to an accelerated aging phenotype that includes earlier than expected brain and peripheral organ damage.
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