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The contribution of immune senescence to this failure is incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to determine the role of pre\u2010ART immune senescence characterized by lymphocyte profile and lymphocyte cellular senescence markers in nonimmune reconstitution (NIR) after 48 weeks of ART initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We first performed a SenMayo gene set score from publicly available CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell scRNA\u2010seq data. Subsequently, a prospective cohort of 510 ART\u2010initiating PLWHIV was assessed at baseline and week 48. IR was strictly defined as a CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell count increase over 350\u2009cells\/uL. Logistic regression; immunophenotyping; cytokine profiling, including TNF\u2010\u03b1, IFN\u2010\u03b3 and CD\u2010107a; and cellular senescence marker, including p16, p21, p53, and senescence\u2010associated \u03b2\u2010galactosidase assessments identified NIR factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bioinformatics analysis revealed multiple ART\u2010na\u00efve CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell subtypes exhibited elevated cellular senescence scores. Patients with IR were significantly younger than those with NIR (both in AIDS and non\u2010AIDS subcohorts,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009 &lt; 0.05). Multivariable analysis indicated age was an independent risk factor for NIR. Before ART initiation, the NIR group exhibited a distinctly senescent immune profile characterized by reduced na\u00efve T cells, increased terminally differentiated T cells, and heightened chronic inflammation with elevated cytokine secretion. ART failed to fully reverse these immune abnormalities, and cellular senescence was most pronounced in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells within the NIR group prior to treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pre\u2010ART immune senescence is strongly associated with NIR in PLWHIV receiving ART. These findings necessitate considering immunological age and immune senescent status for personalized therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jimr\/8683624","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:55:08Z","timestamp":1780401308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Immune Senescence and Immune Reconstitution Among People Living With HIV Undergoing Antiretroviral Therapy"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-4186","authenticated-orcid":false,"given":"Zhe","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huolan","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houji","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-899X","authenticated-orcid":false,"given":"Jian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-9127","authenticated-orcid":false,"given":"Shaohang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002500"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws321"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.045"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/323898"},{"key":"e_1_2_14_5_2","first-page":"16","article-title":"The Prevalence of HIV-Infected Patients with Virological Suppression but a CD4+ T-Cell Count of\u2009\u2264\u2009200 Cells\/mm3 After Highly Active Antiretroviral Therapy Initiation: A Meta-Analysis","volume":"24","author":"Wu Z.","year":"2022","journal-title":"Aids Reviews"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/695852"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27944"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.13017"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-022-07113-y"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600568"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat7911"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042909-093756"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.05.004"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6825493"},{"key":"e_1_2_14_15_2","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1097\/COH.0000000000000077","article-title":"Immunosenescence and Aging in HIV","volume":"9","author":"Tsoukas C.","year":"2014","journal-title":"Current Opinion in HIV and AIDS"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2020.110887"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.06.011"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20210344"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2017.10.024"},{"key":"e_1_2_14_20_2","first-page":"382","article-title":"Role of CD8 T Cell Replicative Senescence in Human Aging and in HIV-Mediated Immunosenescence","volume":"2","author":"Dock J. 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