Untargeted Metabolite Profile Associations With Body Mass Index, Waist–Hip Ratio, and Antiretroviral Therapy in >1300 People With HIV: The Swiss HIV Cohort Study

Background: How obesity and antiretroviral therapy (ART) are associated with specific metabolite profiles in people with HIV (PWH) is not well described. Methods: In Swiss HIV Cohort Study participants, applying multiple linear regression, we analyzed untargeted metabolite profiles and their association with body mass index (BMI), waist–hip ratio (WHR), and current ART categorized based on the “third drug” plus individual ART drugs. Results: We analyzed 1821 metabolites in 1302 PWH (median age 55 years, 78% male, 94% suppressed HIV RNA, median BMI 24.6 kg/m2, 46% overweight/obese). Ninety-four metabolites were associated with BMI, 66 with WHR, and 31 with either BMI or WHR and ART. 156, 173, and 60 metabolites were associated with non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors, respectively. We identified specific patterns of metabolic perturbation for efavirenz, nevirapine, lopinavir, atazanavir, and elvitegravir. Most metabolites associated with tenofovir alafenamide were not associated with tenofovir disoproxil fumarate and vice versa. We found no evidence of any metabolite profiles associated with past zidovudine or stavudine exposure or any interactions between ART drug classes and BMI. Conclusions: In PWH from Switzerland, untargeted metabolite profiling revealed multiple unreported associations with different ART agents, and previously reported associations with BMI.