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Growth differentiation factor 15 (GDF-15) is a mitokine released upon mitochondrial stress and is a validated aging biomarker. Herein, we assessed associations between plasma GDF-15 levels, inflammation, and HIV reservoir markers in ART-treated people with HIV (PWH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood samples were collected from 78 ART-naive, 140 ART-treated PWH (median ART duration, 15.6 years) and 83 uninfected control participants. GDF-15 and markers of inflammation were quantified in plasma by enzyme-linked immunosorbent assay (ELISA) and multiplex assays. Integrated HIV DNA levels were measured in isolated CD4 T cells by ultrasensitive quantitative Alu polymerase chain reaction. Intracellular GDF-15 production was assessed ex vivo by flow cytometry, and in supernatants by ELISA after in vitro stimulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma GDF-15 levels were higher in ART-treated PWH compared to ART-naive PWH or controls, independently of age. Ex vivo, GDF-15 was produced by classical, intermediate, and nonclassical monocytes, but absent in T cells, B cells, natural killer cells, and dendritic cells. Plasma and monocyte intracellular GDF-15 levels correlated strongly (r = 0.96, P = .002). Plasma GDF-15 levels did not correlate with the majority of inflammatory markers quantified in plasma. Conversely, plasma GDF-15 levels correlated with the validated non-AIDS inflammatory comorbidity marker suPAR (soluble urokinase plasminogen activator receptor; r = 0.59, P &amp;lt; .001), as well as with integrated HIV DNA levels in CD4+ T cells (r = 0.47, P &amp;lt; .01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma levels of GDF-15, mainly produced by monocytes, were positively associated with HIV reservoir markers and coincided with increased level of suPAR, suggesting that HIV persistence is associated with increased mitochondrial stress and comorbidity risks in ART-treated PWH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag202","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:51:04Z","timestamp":1775217064000},"page":"e374-e384","source":"Crossref","is-referenced-by-count":4,"title":["Plasma GDF-15 Levels Are Associated With HIV Reservoir Markers Independently of Inflammation in People With HIV on Antiretroviral Therapy"],"prefix":"10.1093","volume":"234","author":[{"given":"Stephane","family":"Isnard","sequence":"first","affiliation":[{"name":"Research Institute, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Chronic Viral Illness Service, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2367-7682","authenticated-orcid":false,"given":"L\u00e9na","family":"Royston","sequence":"additional","affiliation":[{"name":"Research Institute, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Chronic Viral Illness Service, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Geneva University Hospitals Division of Infectious Diseases, , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina A","family":"Berini","sequence":"additional","affiliation":[{"name":"Research Institute, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Chronic Viral Illness Service, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsoarello","family":"Mabanga","sequence":"additional","affiliation":[{"name":"Research Institute, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Chronic Viral Illness Service, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec 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University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Chronic Viral Illness Service, McGill University Health Centre , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Far","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-2607","authenticated-orcid":false,"given":"Am\u00e9lie","family":"Pagliuzza","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montr\u00e9al, Qu\u00e9bec 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A systematic review and meta-analysis","volume":"15","author":"Ron","year":"2024","journal-title":"Front Immunol"},{"key":"2026090212234571100_jiag202-B3","doi-asserted-by":"crossref","first-page":"102865","DOI":"10.1016\/j.arr.2025.102865","article-title":"Pathogens accelerate features of human aging: a review of molecular mechanisms","volume":"112","author":"Proal","year":"2025","journal-title":"Age Res Rev"},{"issue":"Suppl 1","key":"2026090212234571100_jiag202-B4","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1097\/QAI.0000000000002838","article-title":"Aging with grace for people living with HIV: strategies to overcome leaky gut and cytomegalovirus coinfection","volume":"89","author":"Routy","year":"2022","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026090212234571100_jiag202-B5","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.chom.2023.08.006","article-title":"Spontaneous HIV expression during suppressive ART is associated with the 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