Metabolic Reprogramming in HIV+ CD4T-Cells: Implications for Immune Dysfunction and Therapeutic Targets inCo-Infection.

HIV and() co-infection presents a major global health burden. The immune response tois largely orchestrated by cluster of differentiation 4-positive (CD4) T cells, with CD8T cells playing an auxiliary role. This study aims to investigate the immunometabolic response of CD4and CD8T cells toantigens, analysed using metabolomics, to elucidate metabolic shifts that may influence immune function in an HIV+ environment.Whole blood samples from newly diagnosed, treatment-naïve HIV+ individuals were stimulated withantigens early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) using the QuantiFERON(QFT) Gold Plus assay. Following incubation, plasma samples were analysed through untargeted nuclear magnetic resonance (1-NMR) spectroscopy. Metabolomic data were processed using MetaboAnalyst, with differential metabolites identified through multivariate statistical analyses.Metabolic profiling of PBMCs revealed distinct differences in response toantigens between CD4and CD4/CD8T-cell activation. CD4T cells exhibited enhanced glycolysis, with elevated levels of metabolites that are linked largely to the Warburg effect. Additionally, vitamin D levels were found to correlate with certain metabolites, suggesting a role in modulating immune responses.These findings suggest a complex interplay between immune cell metabolism and activation in HIV+ individuals. The study demonstrates that HIV andco-infection significantly influences the broader metabolic profile of peripheral blood mononuclear cells (PBMCs), highlighting the altered metabolic pathways that are critical in immune responses and disease progression. These findings contribute to the understanding of immunometabolism in co-infection and emphasise the need for further research into targeted metabolic interventions.