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

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], alpha = 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, alpha = 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.

Automated summary

This study aimed to determine the association between plasma eicosanoid levels and immune, viral, and cognitive outcomes in people with HIV (PWH). The results showed that plasma eicosanoid concentrations were elevated in PWH and negatively associated with CD4 lymphocyte counts. Higher levels of eicosanoids were also associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated proinflammatory eicosanoids. Despite antiretroviral therapy, plasma eicosanoids remained elevated in PWH.