{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:52:45Z","timestamp":1788562365189,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2022\/SKK12\/UM\/02\/34"],"award-info":[{"award-number":["FRGS\/1\/2022\/SKK12\/UM\/02\/34"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In people living with HIV (PLWH), persistent viral replication and antiretroviral therapy (ART)\u2010associated toxicity contribute to T cell exhaustion, characterised by significant metabolic reprogramming that negatively impacts cellular function and longevity. Understanding the metabolic dysregulation in exhausted T cells could unveil novel therapeutic strategies to rejuvenate immune responses in PLWH. This study investigated the prevalence and metabolic gene expression profiles of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells across three PLWH cohorts: viremic treatment\u2010na\u00efve (TN), viremic treatment\u2010failure (TF) and aviremic treatment\u2010responders (TR). Our analysis revealed that the proportion of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (PD1\n                    <jats:sup>+<\/jats:sup>\n                    CD107a\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) was markedly higher in viremic TN (5.1%) and TF (4.2%) groups compared to the aviremic TR cohort (2.2%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Similarly, the percentage of terminally differentiated T\n                    <jats:sub>EMRA<\/jats:sub>\n                    cells (CCR7\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD45RA\n                    <jats:sup>+<\/jats:sup>\n                    ) was elevated in TN (38.0%) and TF (44.7%) compared with TR (21.5%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), indicating a higher prevalence of late\u2010stage differentiation and exhaustion in viremic individuals. NanoString analysis revealed a broad downregulation of metabolic genes in exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from viremic individuals, suggesting a shift toward a metabolically quiescent state akin to na\u00efve T cells. Seahorse analysis revealed impaired mitochondrial respiration in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from viremic PLWH, characterised by reductions in both ATP\u2010linked respiration and proton leak. Furthermore, we reported that combined treatment with MitoTEMPO and N\u2010acetyl\u2010\n                    <jats:sc>l<\/jats:sc>\n                    \u2010cysteine (NAC) improved mitochondrial function but failed to restore the effector capacity of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. In summary, this study highlights the defective metabolic programming of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in viremic PLWH, underscoring potential metabolic targets for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1111\/imm.70054","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:58:50Z","timestamp":1761703130000},"page":"413-431","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exhausted\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T Cell in\n                    <scp>HIV<\/scp>\n                    Infection Exhibits an Impaired Bioenergetic Metabolism Driven by Mitochondrial Dysfunction"],"prefix":"10.1111","volume":"177","author":[{"given":"Yee Teng","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar Min","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Ying","family":"Phong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting Fang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Howe","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Saeidi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng Choon","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Ying","family":"Cheok","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong Xiang","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"},{"name":"Centre of Excellence for Research in Infectious Diseases and AIDS (CERIA) Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja Iskandar Shah Raja","family":"Azwa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"},{"name":"Centre of Excellence for Research in Infectious Diseases and AIDS (CERIA) Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kian\u2010Kai","family":"Cheng","sequence":"additional","affiliation":[{"name":"Faculty of Chemical and Energy Engineering Universiti Teknologi Malaysia  Johor Bahru Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Yeng","family":"Looi","sequence":"additional","affiliation":[{"name":"School of Biosciences, Faculty of Health &amp; Medical Sciences Taylor's University  Subang Jaya Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeeba","family":"Kamarulzaman","sequence":"additional","affiliation":[{"name":"Monash University Malaysia  Subang Jaya Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Rajasuriar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"},{"name":"Centre of Excellence for Research in Infectious Diseases and AIDS (CERIA) Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-1956","authenticated-orcid":false,"given":"Won Fen","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine Universiti Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Global HIV Statistics \u201cGlobal HIV Statistics\u2014Fact Sheet 2023 \u201d 2023 https:\/\/www.unaids.org\/en\/resources\/fact\u2010sheet."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31819675e9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2055-6640(20)30490-8"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.4709-4722.2002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00291"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.42"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1482"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-849886-6.00016-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.02.012"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.007"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.078"},{"key":"e_1_2_11_15_1","article-title":"Immune Checkpoint Molecules and Glucose Metabolism in HIV\u2010Induced T Cell Exhaustion","volume":"10","author":"Chan Y. 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