Background

HIV infection and normal aging share immune and inflammatory changes that result in premature aging and non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified the common metabolic pathways underlying various NCDs in treated HIV infection.

Methods

We performed untargeted metabolomics including 87 HIV-negative (–) normal controls (NCs), 87 HIV-positive (+) NCs, and 148 HIV+ subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver fibrosis (LF) and renal impairment. All HIV+ subjects were virally suppressed.

Results

HIV+ patients presented widespread alterations in cellular metabolism compared to HIV– NCs. Glycerophospholipid (GPL) metabolism was the only one disturbed pathway presented in comparisons including HIV– NCs across age groups, HIV+ NCs across age groups, HIV+ NCs vs HIV– NCs and each of HIV+ NCDs vs HIV+ NCs. D-glutamine and D-glutamate metabolism and alanine-aspartate-glutamate metabolism were presented in comparisons between HIV+ NCs vs HIV– NCs, HIV+ LF or HIV+ NCI vs HIV+ NCs. Consistently, subsequent analysis identified a metabolomic fingerprint specific for HIV+ NCDs, containing 42 metabolites whose relative abundance showed either an upward (mainly GPL-derived lipid mediators) or a downward trend (mainly plasmalogen phosphatidylcholines, plasmalogen phosphatidylethanolamines, and glutamine) from HIV– NCs to HIV+ NCs and then HIV+ NCDs, reflecting a trend of increased oxidative stress.

Interpretation

GPL metabolism emerges as the common metabolic disturbance linking HIV to NCDs, followed by glutamine and glutamate metabolism. Together, our data point to the aforementioned metabolisms and related metabolites as potential key targets in studying pathophysiology of NCDs in HIV infection and developing therapeutic interventions.

Funding

China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, Yi-wu Institute of Fudan University, and Shanghai Municipal Health and Family Planning Commission.

中文翻译：

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全面的代谢组学分析揭示了治疗 HIV 感染中四种主要非传染性疾病的常见代谢改变

背景

HIV 感染和正常衰老共享导致过早衰老和非传染性疾病 (NCD) 的免疫和炎症变化，但尚未发现确切的病理生理学。我们确定了治疗 HIV 感染中各种 NCD 的常见代谢途径。

方法

我们进行了非靶向代谢组学，包括 87 名 HIV 阴性 (–) 正常对照 (NCs)、87 名 HIV 阳性 (+) NCs 和 148 名 HIV+ 受试者只有一种 NCD，即亚临床颈动脉粥样硬化、神经认知障碍 (NCI)、肝纤维化（LF）和肾功能损害。所有 HIV+ 受试者都受到病毒抑制。

结果

与 HIV-NC 相比，HIV+ 患者的细胞代谢发生了广泛的变化。甘油磷脂 (GPL) 代谢是在比较中出现的唯一一种受干扰的途径，包括跨年龄组的 HIV-NCs、跨年龄组的 HIV+NCs、HIV+NCs与HIV-NCs 以及每个 HIV+NCDs与HIV+NCs 的比较。D-谷氨酰胺和 D-谷氨酸代谢和丙氨酸-天冬氨酸-谷氨酸代谢在 HIV+ NCs与HIV-NCs、HIV+ LF 或 HIV+ NCI与HIV+ NC。一致地，随后的分析确定了 HIV+ NCD 特有的代谢组学指纹，包含 42 种代谢物，其相对丰度显示出来自 HIV-NC 的上升趋势（主要是 GPL 衍生的脂质介质）或下降趋势（主要是缩醛磷脂磷脂酰胆碱、缩醛磷脂磷脂酰乙醇胺和谷氨酰胺）到 HIV+ NCs，然后是 HIV+ NCDs，反映了氧化应激增加的趋势。

解释

GPL 代谢作为将 HIV 与 NCD 联系起来的常见代谢紊乱出现，其次是谷氨酰胺和谷氨酸代谢。总之，我们的数据表明上述代谢和相关代谢物是研究 HIV 感染中非传染性疾病的病理生理学和开发治疗干预措施的潜在关键目标。

资金

国家传染病科技重大专项，国家自然科学基金委员会，复旦大学义乌研究所，上海市卫生计生委。