{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:31:01Z","timestamp":1789594261444,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretar\u00eda de Educaci\u00f3n, Ciencia, Tecnolog\u00eda e Innovaci\u00f3n (SECTEI), Ciudad de M\u00e9xico","award":["SECTEI\/168\/2023"],"award-info":[{"award-number":["SECTEI\/168\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Excessive weight gain is a growing concern among people living with HIV (PWH) receiving integrase strand transfer inhibitor (INSTI)-based regimens as first-line antiretroviral therapy (ART), as it may contribute to multimorbidity. The mechanisms driving weight gain in INSTI users are not fully understood but are thought to be multifactorial. This study examines the plasma metabolome associated with weight gain in PWH on INSTI-based regimens. Methods: We conducted a nested case\u2013control study within the randomized clinical trial MICTLAN (NCT06629480). Sixty-six participants were randomized to receive INSTI-based regimens, either bictegravir\/tenofovir alafenamide\/emtricitabine (BIC\/TAF\/FTC) or dolutegravir\/abacavir\/lamivudine (DTG\/ABC\/3TC), and followed for 18 months. Weight gain &gt;10% relative to baseline was considered a primary endpoint and used as a criterium to categorize cases (n = 28) and controls (n = 38). Anthropometric and clinical measurements, plasma insulin, and metabolomic profiles were assessed at baseline and 18 months post-ART. Plasma untargeted metabolomics was performed using liquid chromatography\u2013mass spectrometry (LC-MS\/MS) to identify metabolomic changes linked to weight gain. Bioinformatic tools, including Partial Least Squares Discriminant Analysis (PLS-DA), volcano plots, and KEGG pathway enrichment analysis, were used to analyze plasma metabolomes and identify significant differential metabolites. Results: Weight gain at 18 months in PWH on INSTI-based ART was associated with insulin resistance, as measured by HOMA-IR (OR 3.23; 95% CI 1.14\u20139.10; p = 0.023), and visceral adipose tissue thickness &gt; 4 cm (OR 4.50; 95% CI 1.60\u201313.03; 9.10; p = 0.004), and hypertriglyceridemia (OR 3.9; 95% CI 1.38\u201310.94; p = 0.008). Baseline HIV RNA viral load &gt;50,000 copies\/mL (OR 8.05; 95% CI 2.65\u201324.43; p = 0.0002) was identified as a baseline predictor of weight gain (aOR 6.58 (1.83\u201323.58); p = 0.004). In addition, accumulation of circulating medium-chain acylcarnitines, indicative of mitochondrial dysfunction, and insulin resistance were linked to weight gain in PWH on INSTI-based regimens after 18 months of therapy. Conclusions: This metabolomic study identified metabolites reflecting mitochondrial dysfunction, dysregulated lipid metabolism, and altered amino acid metabolism as key mechanisms underlying insulin resistance and weight gain in PWH on INSTI-based ART.<\/jats:p>","DOI":"10.3390\/metabo15110695","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:48:46Z","timestamp":1761716926000},"page":"695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolomic Profile of Weight Gain of People Living with HIV Treated with Integrase Strand Transfer Inhibitor Regimens Reveals Dysregulated Lipid Metabolism and Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"given":"Ana Miriam","family":"Ascencio-Anastacio","sequence":"first","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Larios-Serrato","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda y Bioinform\u00e1tica Gen\u00f3mica, Escuela Nacional de Ciencias Biol\u00f3gicas (ENCB), Instituto Polit\u00e9cnico Nacional (IPN), L\u00e1zaro C\u00e1rdenas Professional Unit, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-9894","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Mata-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Rodr\u00edguez Evaristo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireya","family":"N\u00fa\u00f1ez-Armend\u00e1riz","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9659-746X","authenticated-orcid":false,"given":"Ana Luz","family":"Cano-D\u00edaz","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Chaparro-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria Elizabeth","family":"Salinas-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Radiology Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Maldonado-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Infecciosas, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional S.XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3945-4221","authenticated-orcid":false,"given":"Javier","family":"Torres","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Infecciosas, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional S.XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Martha","family":"Garc\u00eda-Flores","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Inmunolog\u00eda, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional S.XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7469-1479","authenticated-orcid":false,"given":"Zuriel Eduardo","family":"Mart\u00ednez-Valencia","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioengineering, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0134-8066","authenticated-orcid":false,"given":"Beatriz Irene","family":"Arroyo-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioengineering, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-807X","authenticated-orcid":false,"given":"Viridiana","family":"Olin-Sandoval","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioengineering, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Minauro","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Gen\u00e9tica Humana, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional S.XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus Enrique","family":"Gayt\u00e1n-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-3703","authenticated-orcid":false,"given":"Ericka Nelly","family":"Pompa-Mera","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Infecciosas, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional S.XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"},{"name":"Research Unit, Hospital de Infectolog\u00eda \u201cDr. Daniel M\u00e9ndez Hern\u00e1ndez\u201d, Centro M\u00e9dico Nacional \u201cLa Raza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kumar, S., and Samaras, K. 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