Untargeted Metabolite profile associations with Body Mass Index, waist-hip ratio, and antiretroviral therapy in >1300 people with HIV: the Swiss HIV Cohort Study
Labarile et al. analyzed the metabolic profiles of 1’302 people with HIV (PWH) in Switzerland to understand how obesity and different antiretroviral therapies (ART) are linked to changes in blood metabolites. The researchers looked at over 1’800 different metabolites and examined their relationships with body mass index (BMI), waist-hip ratio (WHR), and the use of specific ART medications.
Main Outcomes
- The study found 94 metabolites associated with BMI and 66 with WHR in PWH, including several amino acids and lipids. Many of these associations mirrored findings from the general population, suggesting strong links between certain metabolites, obesity, and fat distribution in PWH.
- ART regimens had distinct impacts on participants’ metabolic profiles. For example, non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase inhibitors (INSTIs) each influenced a different set of metabolites.
- The study found that most metabolites associated with tenofovir alafenamide (TAF) were not associated with tenofovir disoproxil fumarate (TDF), and vice versa, suggesting these drugs may have unique impacts on metabolism.
- No strong evidence was found that past exposure to older, more toxic drugs like zidovudine or stavudine had lasting effects on metabolic profiles.
- The effects of individual ART drugs on the metabolome were notable, with certain regimens clustering strongly in analysis, stressing the importance of considering current ART when interpreting metabolomic results in PWH.
Why this matters for people with HIV
Obesity, diabetes, and cardiovascular disease are significant long-term health concerns for people living with HIV. As ART regimens have evolved, newer drugs have been linked to metabolic changes and weight gain. This large, untargeted metabolomic analysis provides new insights into how specific ART agents and obesity markers are tied to biological changes in PWH. The results highlight the need to carefully consider both ART regimen and body weight when studying health outcomes, as both can have strong and sometimes separate effects on metabolism. Ultimately, identifying which metabolites are connected to ART or obesity may help pinpoint those at risk for unhealthy changes—and guide future HIV care towards personalized prevention and treatment strategies.