Work

Integrated multi-omics reveals plasma biomarkers of fatigue in HIV immunological non-responders

Year: 2026

Type: article

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.

Source: Frontiers in Cellular and Infection Microbiology

DOI: 10.3389/fcimb.2026.1932594