Metabolomics Profiling of Antiretroviral Therapy-Associated Metabolic Syndrome in People Living with HIV

Odile Patrick Thalia

Faculty of Biological Sciences Kampala International University Uganda

ABSTRACT

Antiretroviral therapy (ART) has transformed HIV infection into a manageable chronic condition, yet metabolic syndrome (MetS) emerged as a critical comorbidity in people living with HIV (PLHIV), affecting 20–54% of this population compared to 10–25% in the general population. The complex interplayed between viral pathogenesis, immune dysregulation, chronic inflammation, and drug-induced metabolic perturbations necessitates advanced molecular profiling to elucidate underlying mechanisms and identify therapeutic targets. This narrative review critically examined the application of metabolomics in characterizing ART-associated MetS, focusing on mechanistic insights, biomarker discovery, and clinical translation. A comprehensive literature search was conducted using PubMed, Embase, and Web of Science databases (2015–2025), prioritizing metabolomics studies, clinical trials, and mechanistic investigations. Current evidence demonstrated profound alterations in lipid metabolism, particularly increased ceramides, diacylglycerols, and altered sphingolipid profiles, alongside perturbations in branched-chain amino acid catabolism, tricarboxylic acid cycle intermediates, and bile acid homeostasis. Integrase strand transfered inhibitors and protease inhibitors exhibit distinct metabolomic signatures, with the former associated with weight gain through alterations in hypothalamic neuropeptide regulation and adipogenesis pathways. Despite significant advances, metabolomics-guided personalized ART selection remained limited by small cohort sizes, heterogeneous analytical platforms, and insufficient longitudinal validation. Future research must prioritize standardized multi-omics integration, mechanistic validation studies, and biomarker-driven clinical trials to translate metabolomic discoveries into precision medicine approaches that mitigate metabolic complications while maintaining virological efficacy in PLHIV.

Keywords: HIV metabolomics, Antiretroviral therapy, Metabolic syndrome, Lipidomics, Precision medicine.

CITE AS: Odile Patrick Thalia (2026). Metabolomics Profiling of Antiretroviral Therapy-Associated Metabolic Syndrome in People Living with HIV. RESEARCH INVENTION JOURNAL OF RESEARCH IN MEDICAL SCIENCES 5(1):50-61. https://doi.org/10.59298/RIJRMS/2026/515061