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.
Neurology. 2022 Sep 20;99(12):e1251-e1264. doi: 10.1212/WNL.0000000000200945. Epub 2022 Jul 18.
To determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with HIV (PWH).
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.
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.
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.
为了确定血浆花生四烯酸代谢产物水平是否与 HIV 感染者（PWH）的免疫、病毒和认知结果相关。
我们在一项针对 95 名 PWH 和 25 名具有相似人口统计学特征的未感染参与者的纵向研究中测量了 42 种花生四烯酸代谢产物。所有参与者在平均 6.5 个月的 2 次研究访问中接受了常规临床化学、病毒学、免疫标志物以及评估 7 个认知域的神经心理学测试组合。
与血清阴性对照者（n = 25）相比，PWH（n = 95）的血浆花生四烯酸代谢产物浓度升高（在 5%假发现率 [FDR] 下具有 100%的预测能力，α = 0.0531），且与当前和最低 CD4 淋巴细胞计数较低呈负相关。较高的花生四烯酸代谢产物水平与工作记忆、言语流畅性和执行功能受损有关。较高的血浆病毒载量与促炎花生四烯酸代谢产物升高有关（在 5%FDR 下具有 24%的预测能力，在 10%FDR 下具有 42.4%的预测能力，α = 0.10）。纵向分析表明，花生四烯酸代谢产物水平与病毒载量和血浆肌酐相关。尽管花生四烯酸代谢产物与病毒载量相关，但在病毒抑制和未完全抑制的 PWH 中，升高的血浆花生四烯酸代谢产物相似。
这些数据表明，HIV 感染与大量产生花生四烯酸代谢产物相关，而抗逆转录病毒治疗（ART）并不能显著降低这些代谢产物。尽管接受 ART，这些氧化脂类仍持续升高，可能导致加速衰老表型，包括比预期更早的大脑和外周器官损伤。
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