Integrated multi-omics reveals plasma biomarkers of fatigue in HIV immunological non-responders
- 1School of Basic Medicine, Chengdu University of Traditional Chinese Medicine , ,
- 2Traditional Chinese Medicine Department, Jianyang Maternal and Child Health Hospital , ,
Abstract
Objective
To characterize the metabolic and inflammatory signatures distinguishing fatigued from non-fatigued HIV immunological non-responders (INRs) and to explore candidate biomarkers and potential mechanistic pathways underlying HIV-associated fatigue.Methods
We performed untargeted metabolomics and cytokinomics on plasma obtained from 18 fatigued and 17 non-fatigued HIV-INRs. Mechanistic insights were explored via Protein-Protein Interaction (PPI) networks and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.Results
Compared to non-fatigued controls, the fatigued cohort showed significant up-regulation of 4-ketopimelic acid, cholesterol, and 1-hexadecyl-sn-glycero-3-phosphocholine, with concurrent down-regulation of DL-arginine and D-pipecolic acid (P < 0.05). Immunologically, the fatigued group displayed elevated macrophage migration inhibitory factor (MIF) but reduced interferon-induced protein 10 (IP-10/CXCL10) and interleukin-18 (IL-18) levels (P < 0.05). Functional enrichment analysis suggested the involvement of necroptosis, lipid metabolism, and atherosclerosis signaling pathways.Conclusion
Fatigue in HIV-INRs receiving long-term antiretroviral therapy was associated with distinct lipidomic and cytokinomic alterations. These results underscore the potential roles of dysregulated fatty acid metabolism, oxidative stress, and chronic low-grade inflammation in the pathophysiology of fatigue. Cholesterol and IL-18 emerged as candidate biomarkers associated with HIV-associated fatigue; however, their combined discriminatory performance was not statistically validated in this exploratory study and requires confirmation in larger, independent cohorts.
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BibTeX
@article{li2026integrated,
title = {{Integrated multi-omics reveals plasma biomarkers of fatigue in HIV immunological non-responders}},
author = {Baixue Li and Xi Chen and Jibin Liu and Li Wen and Zhengnan Shen and Hang Zhou and Peijie Wu and Quansheng Feng},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1932594},
url = {https://europepmc.org/article/PMC/PMC13716617},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated multi-omics reveals plasma biomarkers of fatigue in HIV immunological non-responders
AU - Baixue Li
AU - Xi Chen
AU - Jibin Liu
AU - Li Wen
AU - Zhengnan Shen
AU - Hang Zhou
AU - Peijie Wu
AU - Quansheng Feng
PY - 2026
DA - 2026/10/15
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1932594
UR - https://europepmc.org/article/PMC/PMC13716617
AB - Objective To characterize the metabolic and inflammatory signatures distinguishing fatigued from non-fatigued HIV immunological non-responders (INRs) and to explore candidate biomarkers and potential mechanistic pathways underlying HIV-associated fatigue.Methods We performed untargeted metabolomics and cytokinomics on plasma obtained from 18 fatigued and 17 non-fatigued HIV-INRs. Mechanistic insights were explored via Protein-Protein Interaction (PPI) networks and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.Results Compared to non-fatigued controls, the fatigued cohort showed significant up-regulation of 4-ketopimelic acid, cholesterol, and 1-hexadecyl-sn-glycero-3-phosphocholine, with concurrent down-regulation of DL-arginine and D-pipecolic acid (P < 0.05). Immunologically, the fatigued group displayed elevated macrophage migration inhibitory factor (MIF) but reduced interferon-induced protein 10 (IP-10/CXCL10) and interleukin-18 (IL-18) levels (P < 0.05). Functional enrichment analysis suggested the involvement of necroptosis, lipid metabolism, and atherosclerosis signaling pathways.Conclusion Fatigue in HIV-INRs receiving long-term antiretroviral therapy was associated with distinct lipidomic and cytokinomic alterations. These results underscore the potential roles of dysregulated fatty acid metabolism, oxidative stress, and chronic low-grade inflammation in the pathophysiology of fatigue. Cholesterol and IL-18 emerged as candidate biomarkers associated with HIV-associated fatigue; however, their combined discriminatory performance was not statistically validated in this exploratory study and requires confirmation in larger, independent cohorts.
SN - 2235-2988
ER -