Untargeted Metabolite Profile Associations with Body Mass Index, Waist-Hip Ratio, and Antiretroviral Therapy in >1300 People with HIV: the Swiss HIV Cohort Study

Marco Labarile^{1

2}, Isabella C Schoepf^{3

4}, Chloé Pasin^{1

2}, Mariam Ait Oumelloul⁵, Christian W Thorball^{5

6}, Carlotta Riebensahm^{7

8}, Bernard Surial⁷, Gilles Wandeler⁷, Dominique L Braun¹, Catia Marzolini^{9

10}, Christian R Kahlert¹¹, Enos Bernasconi¹², Matthias Cavassini¹³, Alexandra Calmy¹⁴, Johannes Nemeth^{1

2}, Lia Bally¹⁵, Peter Reiss¹⁶, Amalio Telenti¹⁷, Bruno Ledergerber¹, Huldrych F Günthard^{1

2}, Jacques Fellay^{6

7}, Nicola Zamboni^{18

19}, Roger D Kouyos^{1

2}, Philip E Tarr³; Swiss HIV Cohort Study

Collaborators, Affiliations

Collaborators

Swiss HIV Cohort Study:
I A Abela, K Aebi-Popp, A Anagnostopoulos, M Battegay, E Bernasconi, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J S Fehr, J Fellay, H Furrer, C A Fux, H F Günthard, A Hachfeld, D H U Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, D Jackson-Perry, C R Kahlert, O Keiser, T Klimkait, R D Kouyos, H Kovari, K Kusejko, N D Labhardt, K Leuzinger, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, J Nemeth, D Nicca, J Notter, P Paioni, G Pantaleo, M Perreau, A Rauch, L P Salazar-Vizcaya, P Schmid, O Segeral, R F Speck, M Stöckle, P E Tarr, A Trkola, G Wandeler, M Weisser, S Yerly

Affiliations

¹ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
² Institute of Medical Virology, University of Zurich, Zurich, 8091 Zurich, Switzerland.
³ University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.
⁴ Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁵ School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
⁶ Precision Medicine Unit, CHUV, University of Lausanne, Switzerland.
⁷ Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁸ Institute of Social and Preventive Medicine, University of Bern, Switzerland.
⁹ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, 4031 Basel, Switzerland.
¹⁰ Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, University Hospital of Lausanne and University of Lausanne, Switzerland.
¹¹ Division of Infectious Diseases, Kantonsspital St Gallen, 9007 St. Gallen, Switzerland.
¹² Division of Infectious Diseases, Ente Ospedaliero Cantonale, University of Geneva and University of Southern Switzerland, 6900 Lugano, Switzerland.
¹³ Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
¹⁴ Division of Infectious Disease, Geneva University Hospital, 1205 Geneva, Switzerland.
¹⁵ Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁶ Department of Global Health and Division of Infectious Disease, Amsterdam University Medical Centers, University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
¹⁷ Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, California, USA.
¹⁸ Swiss Multi-Omics Center, Zurich, Switzerland.
¹⁹ Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.

PMID: 40858302
DOI: 10.1093/infdis/jiaf438

Untargeted Metabolite Profile Associations with Body Mass Index, Waist-Hip Ratio, and Antiretroviral Therapy in >1300 People with HIV: the Swiss HIV Cohort Study

Marco Labarile et al. J Infect Dis. 2025.

. 2025 Aug 27:jiaf438.

doi: 10.1093/infdis/jiaf438. Online ahead of print.

Authors

Collaborators

Swiss HIV Cohort Study:
I A Abela, K Aebi-Popp, A Anagnostopoulos, M Battegay, E Bernasconi, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J S Fehr, J Fellay, H Furrer, C A Fux, H F Günthard, A Hachfeld, D H U Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, D Jackson-Perry, C R Kahlert, O Keiser, T Klimkait, R D Kouyos, H Kovari, K Kusejko, N D Labhardt, K Leuzinger, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, J Nemeth, D Nicca, J Notter, P Paioni, G Pantaleo, M Perreau, A Rauch, L P Salazar-Vizcaya, P Schmid, O Segeral, R F Speck, M Stöckle, P E Tarr, A Trkola, G Wandeler, M Weisser, S Yerly

Affiliations

¹ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
² Institute of Medical Virology, University of Zurich, Zurich, 8091 Zurich, Switzerland.
³ University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.
⁴ Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁵ School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
⁶ Precision Medicine Unit, CHUV, University of Lausanne, Switzerland.
⁷ Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁸ Institute of Social and Preventive Medicine, University of Bern, Switzerland.
⁹ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, 4031 Basel, Switzerland.
¹⁰ Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, University Hospital of Lausanne and University of Lausanne, Switzerland.
¹¹ Division of Infectious Diseases, Kantonsspital St Gallen, 9007 St. Gallen, Switzerland.
¹² Division of Infectious Diseases, Ente Ospedaliero Cantonale, University of Geneva and University of Southern Switzerland, 6900 Lugano, Switzerland.
¹³ Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
¹⁴ Division of Infectious Disease, Geneva University Hospital, 1205 Geneva, Switzerland.
¹⁵ Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Bern, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁶ Department of Global Health and Division of Infectious Disease, Amsterdam University Medical Centers, University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
¹⁷ Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, California, USA.
¹⁸ Swiss Multi-Omics Center, Zurich, Switzerland.
¹⁹ Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.

PMID: 40858302
DOI: 10.1093/infdis/jiaf438

Abstract

Background: Obesity is a major concern in people with HIV (PWH). How obesity and antiretroviral therapy (ART) are associated with specific metabolite profiles in PWH is not well described.

Methods: We included Swiss HIV Cohort Study participants aged ≥45 years. We analyzed untargeted metabolite profiles and their association with BMI, waist-hip ratio (WHR), and ART, both current ART regimen categorized based on the "third drug" plus individual ART drugs. Metabolite profiles were clustered with hierarchical clustering and visualized as heatmaps and Uniform Manifold Approximation and Projection.

Results: We analyzed 1821 putative metabolite ions in 1302 PWH (median age 55 years, 78% male, 94% suppressed HIV RNA, median BMI 24.6kg/m2, 46% overweight/obese). 94 metabolites were associated with BMI and 66 with WHR; the strongest associations were found with amino acids/peptides. 156, 173, and 60 metabolites were associated with exposure to non-nucleoside reverse transcriptase inhibitors, protease-inhibitors, and integrase strand transfer inhibitors, respectively; most associations were found among carbohydrates. 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. 31 metabolites were associated with either BMI or WHR and ART-exposure. We found no evidence of any metabolite profiles associated with past zidovudine or stavudine exposure or any interactions between ART drug classes and BMI, after adjusting for multiple testing.

Discussion: In PWH from Switzerland, untargeted metabolite profiling revealed multiple unreported associations with different ART agents, and previously reported associations with BMI.

Keywords: ART; BMI; HIV infection; multivariable analysis; untargeted metabolite profiles; waist-hip ratio.

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Untargeted Metabolite Profile Associations with Body Mass Index, Waist-Hip Ratio, and Antiretroviral Therapy in >1300 People with HIV: the Swiss HIV Cohort Study

Collaborators

Affiliations

Untargeted Metabolite Profile Associations with Body Mass Index, Waist-Hip Ratio, and Antiretroviral Therapy in >1300 People with HIV: the Swiss HIV Cohort Study

Authors

Collaborators

Affiliations

Abstract

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