Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV

Abstract

Objective.To determine if plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with the human immunodeficiency virus (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 seven cognitive domains was administered to all participants at two study visits over an average of 6.5 months.Results.Plasma eicosanoid concentrations were elevated in PWH (n=95) compared to seronegative controls (n=25) (100% prediction power at 5% FDR, α=0.0531) and in PWH 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 pro-inflammatory 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.Conclusions.These data show that HIV infection is associated with a robust production of eicosanoids that is 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.

Alterations in glutamate, arginine, and energy metabolism characterize cerebrospinal fluid and plasma metabolome of persons with HIV-associated dementia

“…Coherently with an in-vivo deregulation of eicosanoids' metabolism, previous reports suggested that arachidonic acid levels may be increased in the CSF of HIV-1 patients with neurocognitive impairment [21]. Additionally, more recent studies confirmed that plasma eicosanoids are increased in PWH, correlate directly with viral load and negatively with cognitive performances, and are persistently elevated also in ART-treated persons with neurological impairment [24,42].…”

Neuroinflammation and HIV-Associated Cognitive Impairment

“…There are limited studies associating eicosanoids with HIV infection and particularly with HAND. 8 Deme et al 3 show an increase in proinflammatory eicosanoid plasma levels in HIV-infected participants, which was independent from viral load or ART treatment at baseline evaluation (visit 1). However, the eicosanoid plasma levels in HIV-infected participants were associated with lower current and nadir CD4 lymphocyte counts.…”

“…In the brain, HIV infection promotes and perpetuates chronic neuroinflammation with an eventual irreversible brain injury and HIV-associated neurocognitive disorder (HAND). 1,2 In this issue of Neurology, Deme et al 3 published a study evaluating the association between eicosanoids and cognition in an observational cross-sectional and longitudinal cohort of PWH and the way that antiretroviral treatment (ART) modifies this association. The study used clinical data and plasma samples from 95 PWH and 25 matched controls enrolled in the CNS HIV Anti-Retroviral Therapy Effects Research.…”