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The introduction of combination antiretroviral therapy (ART) has dramatically improved life expectancy in human immunodeficiency virus (HIV) infected individuals by suppressing viral replication and increasing CD4<jats:sup>+<\/jats:sup> T\u2010cell counts. Immunosenescence\u2010like changes, including the expansion of memory CD8<jats:sup>+<\/jats:sup> T cells with senescent features, are reported in young HIV\u2010infected individuals who do not have clinically detectable viremia on ART. However, it is less known whether HIV infection affects the immunosenescent status in older HIV\u2010infected individuals. Here, we addressed this question in older HIV\u2010infected, HIV\u2010uninfected, and frail individuals (all groups age \u226565\u2009years) by examining a set of aging\u2010associated genes in peripheral blood mononuclear cells (PBMCs) as well as by analyzing subsets of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells in depth using high\u2010dimensional CyTOF analysis. Older HIV\u2010infected individuals had increased expression of aging\u2010associated genes such as <jats:italic>CX3CR1<\/jats:italic> in PBMCs which are related to IL\u20107 receptor low effector memory (IL\u20107R\u03b1<jats:sup>low<\/jats:sup> EM) CD8<jats:sup>+<\/jats:sup> T cells, a cell population known to expand with age. The subsets of IL\u20107R\u03b1<jats:sup>low<\/jats:sup> EM CD8<jats:sup>+<\/jats:sup> T cells expressing senescent, cytotoxic, and inflammatory molecules, including CD57, perforin, and CX3CR1, as well as memory CD4<jats:sup>+<\/jats:sup> T cells expressing CD161 and CXCR3, molecules associated with replication\u2010competent HIV\u20101 harboring cells, were increased in older HIV\u2010infected individuals. Overall, older HIV\u2010infected individuals without detectable viremia on ART had augmented levels of age\u2010associated immune alterations in PBMCs, suggesting that HIV infection has a persistent impact on senescence in older HIV\u2010infected individuals despite the clinically controlled viremia.<\/jats:p>","DOI":"10.1111\/acel.13702","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T13:15:25Z","timestamp":1661778925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Alterations in high\u2010dimensional T\u2010cell profile and gene signature of immune aging in <scp>HIV<\/scp>\u2010infected older adults without viremia"],"prefix":"10.1111","volume":"21","author":[{"given":"Min Sun","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Jai","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syim","family":"Salahuddin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth R.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brinda","family":"Emu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert C.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7483-1171","authenticated-orcid":false,"given":"Insoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut 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