{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T16:50:58Z","timestamp":1793638258073,"version":"4.5.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prevention and Control of Emerging"},{"name":"Major Infectious Diseases-National Science and Technology Major Project","award":["2025ZD01904900"],"award-info":[{"award-number":["2025ZD01904900"]}]},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Fund for Medical Sciences","award":["2021-I2M-1-037"],"award-info":[{"award-number":["2021-I2M-1-037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Integrase strand transfer inhibitors (INSTI) are recommended as first-line antiretroviral therapy for human immunodeficiency virus (HIV) infection, yet are frequently associated with excessive weight gain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multiomics study on male people with HIV (PWH). A total of 64 male PWH were enrolled and stratified based on their therapeutic history and weight changes over the first year (G1 receiving INSTI with weight gain \u2265 5%; G2 switching to INSTI with weight gain \u2265 5%; and G3 switching to INSTI without weight gain). Integrase strand transfer inhibitor-based regimens included bictegravir-, elvitegravir-, and dolutegravir-containing combinations. Twenty-six healthy male controls were also included. Plasma untargeted metabolomics and proteomics were analyzed longitudinally. Machine learning models were employed to integrate multiomics data and identify predictive biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Metabolomic analysis revealed that switching to INSTI induced a generalized hypometabolic state, characterized by a universal decline in thyroxine and an increase in N-acetylputrescine across all switching groups, independent of weight outcomes. In contrast, proteomic profiling identified distinct molecular drivers specific to the weight-gain groups. Random forest modeling identified transthyretin (TTR) as the top predictive biomarker among pre-INSTI multiomics features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our integrated multiomics approach reveals that INSTI-based regimens induce universal metabolic changes. The change of thyroxine and the predictability of TTR in multiomics studies show the critical role of thyroxine metabolism in INSTI-associated weight gain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag385","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:52:43Z","timestamp":1784807563000},"source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Mechanisms of Integrase Strand Transfer Inhibitor-Associated Weight Gain: A Multiomics Study in Male People With HIV"],"prefix":"10.1093","author":[{"given":"Xin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leidan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fada","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-5675","authenticated-orcid":false,"given":"Taisheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]},{"name":"Center for AIDS Research, Chinese Academy of Medical Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-7493","authenticated-orcid":false,"given":"Wei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026081021265937600_jiag385-B1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12977-022-00608-1","article-title":"A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection","volume":"19","author":"Zhao","year":"2022","journal-title":"Retrovirology"},{"key":"2026081021265937600_jiag385-B2","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.3390\/jcm10163456","article-title":"Do all integrase strand transfer inhibitors have the same lipid profile? 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