Longitudinal Serum Metabolomic Signatures Related to Integrase Strand-Transfer Inhibitors-Associated Weight Gain in Women With HIV Enrolled in the MACS/WIHS Combined Cohort Study
Year: 2026
Type: article
Abstract: BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH), particularly in women with HIV (WWH), but underlying mechanisms remain unclear. We used longitudinal untargeted metabolomics to identify metabolic signatures of INSTI-related weight gain in WWH. METHODS: We analyzed serum from 192 participants in the Women's Interagency HIV Study: 38 virologically suppressed WWH who initiated INSTIs (INSTI group), 88 virologically suppressed WWH who remained on their original antiretroviral therapy (non-INSTI group), and 66 women without HIV (WWoH). Samples were collected at baseline (6-12 months before INSTI initiation), 1-6 months post-initiation, and 1-2 years post-initiation, with matched visits for controls. High-resolution metabolomics was performed by liquid chromatography-mass spectrometry. Within each group, linear mixed-effects models adjusted for baseline age and BMI compared longitudinal metabolite changes between weight gainers and maintainers, and significant features were analyzed by Mummichog v2.0 pathway enrichment. RESULTS: Mean age was 45.7 ± 8.9 years and mean BMI 32.4 ± 8.3 kg/m2, with no differences across groups; within each group, gainers and maintainers were demographically comparable (p > 0.05). In the INSTI group, metabolites differentiating gainers from maintainers were enriched in 16 pathways across timepoints, predominantly lipid-related (56%), including the polyunsaturated fatty acid (PUFA) pathways linoleic acid and arachidonic acid metabolism. In the non-INSTI and WWoH groups, differentiating metabolites spanned a broader range of pathways, including amino acid metabolism. CONCLUSIONS: Weight gain among INSTI-treated WWH is characterized by a distinct, lipid- and PUFA-dominated metabolic profile, providing mechanistic insight that may inform therapeutic strategies.
Authors: Chin-An Yang, Young-Mi Go, Dean P Jones, Brahmchetna Bedi, Qian Yang, C Christina Mehta, Igho Ofotokun, Anandi N Sheth, Mohammed K Ali, Sami Teeny, Maria L Alcaide, Frank J Palella, Jordan E Lake, Leah H Rubin, Elizabeth F Topper, Julie Schexnayder, Anjali Sharma, Julie B Dumond, Jennifer Cocohoba, Seble G Kassaye, Michael Augenbraun, Audrey French, Thomas R Ziegler, Jessica A Alvarez, Cecile D Lahiri
Institutions: Emory University, University of Miami, University of Miami Health System, Northwestern University, The University of Texas Health Science Center at Houston, Johns Hopkins University, University of Alabama at Birmingham, Albert Einstein College of Medicine, University of North Carolina at Chapel Hill, University of California, San Francisco, Georgetown University, SUNY Downstate Health Sciences University, University of Illinois Chicago
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Funders: NHS Innovation Accelerator, Georgia Clinical and Translational Science Alliance, National Institute of Development Administration, National Institutes of Health, University of California, San Francisco, Center for AIDS Research, University of Alabama at Birmingham, National Cancer Institute, Cairo University, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Nursing Research, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, Office of AIDS Research, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Center for AIDS Research, University of North Carolina at Chapel Hill, NOAA Research, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: Translational Biomedical Science Training Grant, Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS), G2247312219, G2462492050, G2682576363, G4119783234, G4322643608, G4654328136, Clinical and Translational Science Institute, G614941763, G6320762085, University of Miami Developmental HIV/AIDS Mental Health Research Center (D-ARC), G6902054257, G6945880900, Institutional Career Development Core, G7572942959, Johns Hopkins Institute for Clinical and Translational Research, G8640572611, University of Pittsburgh MACS/WIHS CCS, MACS/WIHS -CCS, ERC Einstein-Rockefeller-CUNY Center for AIDS research, SF Bay Area MACS/WIHS Combined Cohort Study, UNC MACS/WIHS Combined Cohort Study Clinical Research Site, Mentoring in Sex and Gender-informed Multidisciplinary Research on Cardiometabolic Comorbidities in Persons with HIV, Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studies, Center for AIDS Research at Emory University, Northwestern CORE Clinical Research Site: Trans-omics for HIV/AIDS Research, Los Angeles CRS for the MACS/WIHS Combined Cohort Study, Data Analysis and Coordination Center for the MACS-WIHS Combined Cohort Study, MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS), SPPACE INSTI Study: Sex-specific Predictors, Pathways, And Cardiometabolic Effects of Weight Gain Associated with Integrase Strand-Transfer Inhibitors, The University of North Carolina Center for AIDS Research, MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS), Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center, Atlanta MACS/WIHS Combined Cohort Study Clinical Research Site, UAB-MISS MACS/WIHS Combined Cohort Study, Miami Center for AIDS Research, UCLA Clinical and Translational Science Institute, Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS), UAB Center for AIDS Research (CFAR)
OpenAlex ID: W7166529266