Antiretroviral treatment affects HIV/TB individuals differently based on sex: A GC MS metabolomics proof of concept study

ABSTRACT: Introduction: Human immunodeficiency virus (HIV) and tuberculosis (TB) coinfection presents complex treatment challenges, with growing evidence that sex-specific metabolic responses influence antiretroviral treatment (ART) effectiveness. Metabolomic profiling offers a powerful tool to elucidate these biochemical differences, paving the way for more precise, sex-informed therapeutic strategies in coinfected individuals. Aim: To characterise sex-specific metabolic alterations associated with ART in HIV/TB coinfected individuals using non-targeted urine metabolomics. Methods: Urine samples (n = 27) were analysed using gas chromatography–mass spectrometry (GC–MS) in two experimental setups: individual sampling (Experiment 1) and pooled sampling (Experiment 2), implemented due to limited sample size. Univariate statistical analyses included pairwise comparisons, fold-change analysis, and effect size calculation. Non-parametric tests (Wilcoxon rank-sum and Kruskal–Wallis) were used to evaluate significant multi-group differences. Results: Distinct sex-related metabolic patterns were identified, comprising 51 significantly altered metabolites. Males exhibited greater mitochondrial-associated metabolic dysregulation, including elevated Krebs cycle intermediates, ketone bodies, and oxidative stress-related markers. Females showed enhanced amino acid turnover, increased nitrogen clearance, and higher detoxification-linked metabolites. Microbial metabolism also differed, with evidence of dysbiosis and microbial overgrowth in females, and impaired tryptophan metabolism in males. These findings likely reflect complex host–microbial metabolic interactions under ART. Conclusion: This study underscores the importance of considering biological sex in metabolomic assessments of HIV/TB coinfection. The findings provide novel insight into sex-specific biochemical responses to ART, particularly regarding mitochondrial and microbial-linked metabolic health in coinfected individuals.

ORGANISM(S): Homo sapiens (human)

SUBMITTER: Bianca Allen 

PROVIDER: S-BSST2261 | biostudies-other |

REPOSITORIES: biostudies-other