{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:13Z","timestamp":1787026573258,"version":"build-2736575974"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Advances in antiretroviral therapy (ART) have substantially improved the lives of people with HIV (PWH) and reduced HIV acquisition through pre-exposure prophylaxis (PrEP). However, the long-term effect of ART on the physiological state of cells remains poorly understood and PWH are currently suffering from a disproportionate burden of non-AIDS comorbidities, including lung diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Given the central function of alveolar macrophages (AM) in pulmonary immunity, we evaluated the impact of ART on AM of PWH and people on PrEP using a systems immunology approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We showed that continuous ART induces a progressive senescence-like pro-inflammatory state in AM characterized by increased constitutive epigenetic and transcriptomic priming of genes involved in cell-cycle arrest and senescence. At the AM single nucleus level, we discovered a coordinated gene regulatory network linking key pro-inflammatory transcription factors to the alterations induced by ART. The senescence ART-linked changes were strongly dependent on the duration of ART and irrespective of HIV infection. A secondary time independent ART-effect was observed for interferon signaling which impaired the AM response to ex vivo challenge with SARS-CoV-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our data indicated that continuous ART promoted a dysregulated physiological state in AM. The results of our study advocate for optimized or adjuvant therapies to mitigate potential long-term adverse ART-effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1805936","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:51:59Z","timestamp":1776837119000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Continuous antiretroviral therapy induces progressive senescence-like reprogramming of alveolar macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Vinicius M.","family":"Fava","sequence":"first","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"McGill International TB Centre, McGill University","place":["Montreal, QC, Canada"]},{"name":"Canadian Centre for Computational Genomics (C3G) McGill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Dallmann-Sauer","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"McGill International TB Centre, McGill University","place":["Montreal, QC, Canada"]},{"name":"Departments of Human Genetics and Medicine, Faculty of Medicine, McGill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Orlova","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"McGill International TB Centre, McGill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilian","family":"Correa-Macedo","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"McGill International TB Centre, McGill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Olivenstein","sequence":"additional","affiliation":[{"name":"Translational Research in Respiratory Diseases Program, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia Theresa","family":"Costiniuk","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"Department of Medicine and Chronic Viral Illnesses Service, McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"Graduate Program in Clinical and Translational Research, McGill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Routy","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"Department of Medicine and Chronic Viral Illnesses Service, McGill University Health Centre","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis B.","family":"Barreiro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Genetic Section, University of Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Schurr","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre","place":["Montreal, QC, Canada"]},{"name":"McGill International TB Centre, McGill University","place":["Montreal, QC, Canada"]},{"name":"Departments of Human Genetics and Medicine, Faculty of Medicine, McGill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12403","article-title":"The evolution of three decades of antiretroviral therapy: challenges, triumphs and the promise of the future","volume":"79","author":"Tseng","year":"2015","journal-title":"Br J Clin Pharmacol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/coh.0000000000000810","article-title":"Decrypting biological hallmarks of aging in people with HIV","volume":"18","author":"Premeaux","year":"2023","journal-title":"Curr Opin HIV AIDS"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/09540121.2012.712669","article-title":"Chronic illness burden and quality of life in an aging HIV population","volume":"25","author":"Balderson","year":"2013","journal-title":"AIDS Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-041734","article-title":"Excess burden of age-associated comorbidities among people living with HIV in British Columbia, Canada: a population-based cohort study","volume":"11","author":"Nanditha","year":"2021","journal-title":"BMJ Open"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-018-0201-6","article-title":"A review of long-term toxicity of antiretroviral treatment regimens and implications for an aging population","volume":"7","author":"Chawla","year":"2018","journal-title":"Infect Dis Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/qad.0000000000001712","article-title":"Pulmonary disease in HIV-infected adults in the era of antiretroviral therapy","volume":"32","author":"Fitzpatrick","year":"2018","journal-title":"AIDS"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201006-0836oc","article-title":"HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era","volume":"183","author":"Crothers","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s2666-7568(23)00037-5","article-title":"Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years","volume":"4","author":"Schoepf","year":"2023","journal-title":"Lancet Healthy Longev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.08.006","article-title":"Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4(+) and CD8(+) T cells","volume":"31","author":"Dube","year":"2023","journal-title":"Cell Host Microbe"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/qad.0000000000002275","article-title":"HIV-mediated immune aging in young adults infected perinatally or during childhood","volume":"33","author":"Fastenackels","year":"2019","journal-title":"AIDS"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa599","article-title":"Occurrence of accelerated epigenetic aging and methylation disruptions in human immunodeficiency virus infection before antiretroviral therapy","volume":"223","author":"Yang","year":"2021","journal-title":"J Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009785","article-title":"Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART","volume":"17","author":"Corley","year":"2021","journal-title":"PloS Pathog"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/s2214-109x(17)30451-5","article-title":"Prevalence of chronic obstructive pulmonary disease in the global population with HIV: a systematic review and meta-analysis","volume":"6","author":"Bigna","year":"2018","journal-title":"Lancet Glob Health"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.864838","article-title":"Systematic review and meta-analyses of the interaction between HIV infection and COVID-19: two years\u2019 evidence summary","volume":"13","author":"Wang","year":"2022","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-3018(22)00097-2","article-title":"Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19","volume":"9","author":"Bertagnolio","year":"2022","journal-title":"Lancet HIV"},{"key":"B16","article-title":"Global tuberculosis report 2023","year":"2023"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/jci148013","article-title":"Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis","volume":"131","author":"Correa-Macedo","year":"2021","journal-title":"J Clin Invest"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(04)01060-6","article-title":"Global strategies to prevent bacterial pneumonia in adults with HIV disease","volume":"4","author":"Feikin","year":"2004","journal-title":"Lancet Infect Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2019.1634546","article-title":"Treating bacterial pneumonia in people living with HIV","volume":"13","author":"Zifodya","year":"2019","journal-title":"Expert Rev Respir Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00359-2018","article-title":"Increasing burden of noninfectious lung disease in persons living with HIV: a 7-year study using the French nationwide hospital administrative database","volume":"52","author":"Maitre","year":"2018","journal-title":"Eur Respir J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-3018(22)00219-3","article-title":"Trends and risk of lung cancer among people living with HIV in the USA: a population-based registry linkage study","volume":"9","author":"Haas","year":"2022","journal-title":"Lancet HIV"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/coh.0000000000000326","article-title":"Lung cancer in persons with HIV","volume":"12","author":"Sigel","year":"2017","journal-title":"Curr Opin HIV AIDS"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201202-0320st","article-title":"An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease","volume":"185","author":"Meyer","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s13073-021-00986-9","article-title":"A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Quebec, Canada","volume":"13","author":"Murall","year":"2021","journal-title":"Genome Med"},{"key":"B25","first-page":"060012","article-title":"An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation","volume-title":"bioRxiv","author":"Sergushichev","year":"2016"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1025","article-title":"The reactome pathway knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"4827","DOI":"10.1038\/s41467-022-32552-1","article-title":"A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues","volume":"13","author":"Saul","year":"2022","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-12-0871","article-title":"p21-mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress","volume":"15","author":"Charrier-Savournin","year":"2004","journal-title":"Mol Biol Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3706","article-title":"GADD45 induction of a G2\/M cell cycle checkpoint","volume":"96","author":"Wang","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mju045","article-title":"CHK2 kinase in the DNA damage response and beyond","volume":"6","author":"Zannini","year":"2014","journal-title":"J Mol Cell Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2784","article-title":"A complex secretory program orchestrated by the inflammasome controls paracrine senescence","volume":"15","author":"Acosta","year":"2013","journal-title":"Nat Cell Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105089","article-title":"Targeted plasma proteomics reveals upregulation of distinct inflammatory pathways in people living with HIV","volume":"25","author":"Vadaq","year":"2022","journal-title":"iScience"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2020.05.019","article-title":"Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4(+) T cell counts <350 cells\/mm(3) - a potential hallmark of chronic inflammation","volume":"22","author":"Ellwanger","year":"2020","journal-title":"Microbes Infect"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00281","article-title":"Astrocyte senescence and metabolic changes in response to HIV antiretroviral therapy drugs","volume":"9","author":"Cohen","year":"2017","journal-title":"Front Aging Neurosci"},{"key":"B36","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s41572-023-00450-5","article-title":"HIV-associated lung disease","volume":"9","author":"Konstantinidis","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32158","article-title":"Advanced stage at diagnosis and elevated mortality among US patients with cancer infected with HIV in the National Cancer Data Base","volume":"125","author":"Coghill","year":"2019","journal-title":"Cancer"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/jci125366","article-title":"Fra-2-expressing macrophages promote lung fibrosis in mice","volume":"129","author":"Ucero","year":"2019","journal-title":"J Clin Invest"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109408","article-title":"Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases","volume":"64","author":"Birnhuber","year":"2019","journal-title":"Cell Signal"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.4874","article-title":"Role of IL-6 in asthma and other inflammatory pulmonary diseases","volume":"8","author":"Rincon","year":"2012","journal-title":"Int J Biol Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2021-001857","article-title":"Diagnosis values of IL-6 and IL-8 levels in serum and bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in chronic obstructive pulmonary disease","volume":"69","author":"Liu","year":"2021","journal-title":"J Investig Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12931-024-02703-7","article-title":"Upregulated microRNA-125b-5p in patients with asthma-COPD overlap mediates oxidative stress and late apoptosis via targeting IL6R\/TRIAP1 signaling","volume":"25","author":"Chang","year":"2024","journal-title":"Respir Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Lopez-Otin","year":"2023","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101544","article-title":"Oxidative stress-based therapeutics in COPD","volume":"33","author":"Barnes","year":"2020","journal-title":"Redox Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03651-8","article-title":"Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells","volume":"595","author":"Casanova-Acebes","year":"2021","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07711-z","article-title":"Integrative multi-omics identifies AP-1 transcription factor as a targetable mediator of acquired osimertinib resistance in non-small cell lung cancer","volume":"16","author":"Dayanc","year":"2025","journal-title":"Cell Death Dis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s12935-019-0937-4","article-title":"The role of MDM2 amplification and overexpression in therapeutic resistance of Malignant tumors","volume":"19","author":"Hou","year":"2019","journal-title":"Cancer Cell Int"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-19-3674","article-title":"BRD4 levels determine the response of human lung cancer cells to BET degraders that potently induce apoptosis through suppression of Mcl-1","volume":"80","author":"Zong","year":"2020","journal-title":"Cancer Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.808722","article-title":"Pulmonary immune dysregulation and viral persistence during HIV infection","volume":"12","author":"Alexandrova","year":"2021","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41392-022-01106-8","article-title":"Alveolar macrophages: Achilles\u2019 heel of SARS-CoV-2 infection","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ircmb.2022.01.001","article-title":"Pulmonary macrophages and SARS-Cov2 infection","volume":"367","author":"Bain","year":"2022","journal-title":"Int Rev Cell Mol Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-1639631\/v1","article-title":"Immediate myeloid depot for SARS-CoV-2 in the human lung","volume":"10","author":"Magnen","year":"2024","journal-title":"Sci Adv"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.002","article-title":"Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis","volume":"186","author":"Kotov","year":"2023","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"Bastard","year":"2020","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-023-01512-9","article-title":"Autoantibodies neutralizing type I IFNs in the bronchoalveolar lavage of at least 10% of patients during life-threatening COVID-19 pneumonia","volume":"43","author":"Philippot","year":"2023","journal-title":"J ClinImmunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/s2055-6640(20)30312-5","article-title":"How safe is TDF\/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP","volume":"4","author":"Pilkington","year":"2018","journal-title":"J Virus Erad"},{"key":"B57","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1056\/nejmoa1108524","article-title":"Antiretroviral prophylaxis for HIV prevention in heterosexual men and women","volume":"367","author":"Baeten","year":"2012","journal-title":"N Engl J Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0464","article-title":"HIV preexposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate among cisgender women","volume":"331","author":"Marrazzo","year":"2024","journal-title":"JAMA"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-3018(23)00268-0","article-title":"Impact of HIV self-testing for oral pre-exposure prophylaxis scale-up on drug resistance and HIV outcomes in western Kenya: a modelling study","volume":"11","author":"Cox","year":"2024","journal-title":"Lancet HIV"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(13)61127-7","article-title":"Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial","volume":"381","author":"Choopanya","year":"2013","journal-title":"Lancet"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-2667(22)00106-2","article-title":"Real-world effectiveness of pre-exposure prophylaxis in men at high risk of HIV infection in France: a nested case-control study","volume":"7","author":"Jourdain","year":"2022","journal-title":"Lancet Public Health"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100096","article-title":"Treatment with commonly used antiretroviral drugs induces a type I\/III interferon signature in the gut in the absence of HIV infection","volume":"1","author":"Hughes","year":"2020","journal-title":"Cell Rep Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01755-20","article-title":"In vitro exposure of leukocytes to HIV preexposure prophylaxis decreases mitochondrial function and alters gene expression profiles","volume":"65","author":"Bowman","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"B64","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.mad.2018.07.008","article-title":"HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs","volume":"175","author":"Cohen","year":"2018","journal-title":"Mech Ageing Dev"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01941-21","article-title":"Anti-HIV drugs cause mitochondrial dysfunction in monocyte-derived macrophages","volume":"66","author":"Wallace","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit006","article-title":"Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging","volume":"207","author":"Leeansyah","year":"2013","journal-title":"J Infect Dis"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.04.039","article-title":"Exosome-based delivery of super-repressor IkappaBalpha ameliorates kidney ischemia-reperfusion injury","volume":"100","author":"Kim","year":"2021","journal-title":"Kidney Int"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14060645","article-title":"Effects of NF-kappaB inhibitor on sepsis depend on the severity and phase of the animal sepsis model","volume":"14","author":"Park","year":"2024","journal-title":"J Pers Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01388-8","article-title":"Exosome-based targeted delivery of NF-kappaB ameliorates age-related neuroinflammation in the aged mouse brain","volume":"57","author":"Lee","year":"2025","journal-title":"Exp Mol Med"},{"key":"B70","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41573-023-00848-6","article-title":"Targeting hypoxia-inducible factors: therapeutic opportunities and challenges","volume":"23","author":"Yuan","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14246054","article-title":"Hypoxia-inducible factor-1: a novel therapeutic target for the management of cancer, drug resistance, and cancer-related pain","volume":"14","author":"Bui","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1172\/jci159839","article-title":"Hypoxia-inducible factors: cancer progression and clinical translation","volume":"132","author":"Wicks","year":"2022","journal-title":"J Clin Invest"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01923-y","article-title":"Cellular senescence and senolytics: the path to the clinic","volume":"28","author":"Chaib","year":"2022","journal-title":"Nat Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr1719","article-title":"Senolytic treatment for low back pain","volume":"11","author":"Mannarino","year":"2025","journal-title":"Sci Adv"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01963-9","article-title":"HIV pre-exposure prophylaxis: new and upcoming drugs to address the HIV epidemic","volume":"83","author":"Rivera","year":"2023","journal-title":"Drugs"},{"key":"B76","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1056\/nejmoa2101016","article-title":"Cabotegravir for HIV prevention in cisgender men and transgender women","volume":"385","author":"Landovitz","year":"2021","journal-title":"N Engl J Med"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00538-4","article-title":"Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial","volume":"399","author":"Delany-Moretlwe","year":"2022","journal-title":"Lancet"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1056\/nejme2204376","article-title":"Lenacapavir for HIV-1 - potential promise of a long-acting antiretroviral drug","volume":"386","author":"Marrazzo","year":"2022","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1805936\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:52:04Z","timestamp":1776837124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1805936\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":78,"alternative-id":["10.3389\/fimmu.2026.1805936"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1805936","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]},"article-number":"1805936"}}