Department of Internal Medicine, Division Infectious Diseases, Erasmus Medical Center, Wytemaweg 80, 3015 CE, Rotterdam, The Netherlands.
Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Wytemaweg 80, 3015 CE, Rotterdam, The Netherlands.
Sci Rep. 2018 Nov 16;8(1):16947. doi: 10.1038/s41598-018-35271-0.
The HIV-human metabolic relationship is a complex interaction convoluted even more by antiretroviral therapy (cART) and comorbidities. The ability of cART to undo the HIV induced metabolic dysregulation is unclear and under-investigated. Using targeted metabolomics and multiplex immune biomarker analysis, we characterized plasma samples obtained from 18 untreated HIV-1-infected adult patients and compared these to a non-HIV infected (n = 23) control population. The biogenic amine perturbations during an untreated HIV infection implicated altered tryptophan- nitrogen- and muscle metabolism. Furthermore, the lipid profiles of untreated patients were also significantly altered compared to controls. In untreated HIV infection, the sphingomyelins and phospholipids correlated negatively to markers of infection IP-10 and sIL-2R whereas a strong association was found between triglycerides and MCP-1. In a second cohort, we characterized plasma samples obtained from 28 HIV-1-infected adult patients before and 12 months after the start of cART, to investigate the immune-metabolic changes associated with cART. The identified altered immune-metabolic pathways of an untreated HIV infection showed minimal change after 12 months of cART. In conclusion, 12 months of cART impacts only mildly on the metabolic dysregulation underlying an untreated HIV infection and provide insights into the comorbidities present in virally suppressed HIV patients.
HIV 与人体代谢的关系非常复杂,抗逆转录病毒疗法 (cART) 和合并症使这种关系更加复杂。cART 消除 HIV 引起的代谢失调的能力尚不清楚,也未得到充分研究。本研究使用靶向代谢组学和多重免疫生物标志物分析,对 18 名未经治疗的 HIV-1 感染成年患者的血浆样本进行了特征描述,并将其与未感染 HIV 的对照组(n = 23)进行了比较。未经治疗的 HIV 感染期间生物胺的改变提示色氨酸-氮代谢和肌肉代谢发生改变。此外,未经治疗的患者的脂质谱与对照组相比也有明显改变。在未经治疗的 HIV 感染中,鞘磷脂和磷脂与感染标志物 IP-10 和 sIL-2R 呈负相关,而甘油三酯与 MCP-1 之间存在强烈关联。在第二个队列中,我们对 28 名 HIV-1 感染成年患者在开始 cART 前和 12 个月后的血浆样本进行了特征描述,以研究与 cART 相关的免疫代谢变化。未经治疗的 HIV 感染中确定的改变的免疫代谢途径在 cART 12 个月后变化很小。总之,cART 治疗 12 个月仅对未治疗的 HIV 感染引起的代谢失调产生轻微影响,并为了解病毒抑制的 HIV 患者中存在的合并症提供了依据。