{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:49:19Z","timestamp":1791488959555,"version":"4.3.4"},"reference-count":32,"publisher":"American Society of Tropical Medicine and Hygiene","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,8]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Immunological discordance, the persistence of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell depletion despite sustained virological suppression on antiretroviral therapy (ART) in people with HIV, remains incompletely characterized in the contemporary integrase strand transfer inhibitor (INSTI) era. A multicenter, retrospective cohort study was conducted through chart review at four Turkish tertiary infectious diseases units across three regions. Adults with HIV-1 who had received ART for at least 12 consecutive months were eligible. The primary outcome was immunological discordance, defined as a current CD4\n                    <jats:sup>+<\/jats:sup>\n                    count &lt;350 cells\/\n                    <jats:italic>\u00b5<\/jats:italic>\n                    L despite plasma HIV-1 RNA &lt;50 copies\/mL. Associations were examined using Firth-penalized logistic regression with bootstrap internal validation and E-value sensitivity analysis. Among 207 participants (median age 38 years, 85.5% male, 99.0% on INSTI-based regimens), 23 (11.1%; 95% CI: 7.5\u201316.2) had immunological discordance, 180 (87.0%) had concordant responses, three (1.4%) had virological discordance (HIV-1 RNA \u226550 copies\/mL despite CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2265350 cells\/\n                    <jats:italic>\u00b5<\/jats:italic>\n                    L), and one (0.5%) had dual nonresponse. In the multivariable Firth-penalized analysis, advanced disease at diagnosis (adjusted odds ratio: 5.74; 95% CI: 2.08\u201316.34), age greater than 50 years (3.71; 1.25\u201311.07), and previous AIDS-defining opportunistic infection (3.42; 1.09\u201310.85) were independent predictors of immunological discordance (area under the curve: 0.81; optimism-corrected: 0.78). In this contemporary INSTI-treated cohort, approximately one in nine virologically suppressed patients failed to achieve adequate CD4\n                    <jats:sup>+<\/jats:sup>\n                    recovery. Late HIV diagnosis emerged as the principal modifiable upstream driver of incomplete immune recovery, reinforcing the need for earlier diagnosis and rapid linkage to care in T\u00fcrkiye.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.26-0399","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:52:07Z","timestamp":1791485527000},"source":"Crossref","is-referenced-by-count":0,"title":["Immunological Discordance in People with HIV Receiving Contemporary Integrase Inhibitor-Based Antiretroviral Therapy: A Multicenter Retrospective Cohort Study from T\u00fcrkiye"],"prefix":"10.4269","author":[{"given":"Enes","family":"Dalmano\u011flu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bal\u0131kesir University, Bal\u0131kesir, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u015fim","family":"\u00c7a\u011flar","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bal\u0131kesir University, Bal\u0131kesir, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukiye","family":"\u0130nan Sar\u0131kaya","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bal\u0131kesir University, Bal\u0131kesir, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sel\u00e7uk","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, \u00c7anakkale Onsekiz Mart University, \u00c7anakkale, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Erdem K\u0131vrak","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Manisa Celal Bayar University, Manisa, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayten","family":"Yan\u0131k","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Erzurum City Hospital, Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fclce Eyl\u00fcl","family":"Aldemir","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bal\u0131kesir University, Bal\u0131kesir, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serenay","family":"\u00c7akmak Uzun","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, \u00c7anakkale Onsekiz Mart University, \u00c7anakkale, T\u00fcrkiye;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","article-title":"Global HIV Statistics: Fact Sheet 2025","year":"2025"},{"key":"b2","article-title":"HIV Data and Statistics 2025","year":"2025"},{"issue":"4","key":"b3","series-title":"Curr HIV Res","first-page":"258","article-title":"Temporal trends in the epidemiology of HIV in Turkey","volume":"18","author":"Erdinc","year":"2020"},{"issue":"3","key":"b4","series-title":"Cent Eur J Public Health","first-page":"229","article-title":"Late presentation among patients with human immunodeficiency virus infection in Turkey","volume":"27","author":"Karaosmano\u011flu","year":"2019"},{"issue":"1","key":"b5","series-title":"Curr HIV Res","first-page":"60","article-title":"Epidemiological profile of naive HIV-1\/AIDS patients in Istanbul: The largest case series from 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A systematic review and meta-analysis","volume":"15","author":"Ron","year":"2024"},{"issue":"5","key":"b26","series-title":"PLoS Pathog","first-page":"e1004078","article-title":"HIV-infected individuals with low CD4\/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality","volume":"10","author":"Serrano-Villar","year":"2014"},{"key":"b27","series-title":"EBioMedicine","first-page":"104773","article-title":"Expanding HIV clinical monitoring: The role of CD4, CD8, and CD4\/CD8 ratio in predicting non-AIDS events","volume":"95","author":"Mart\u00ednez-Sanz","year":"2023"},{"issue":"3","key":"b28","series-title":"Lancet HIV","first-page":"e98","article-title":"CD4\/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: An observational cohort study","volume":"2","author":"Mussini","year":"2015"},{"issue":"1","key":"b29","series-title":"Expert Rev Anti Infect Ther","first-page":"29","article-title":"Discordant responses to cART in HIV-1 patients in the era of high potency antiretroviral drugs: Clinical evaluation, classification, management prospects","volume":"14","author":"Cenderello","year":"2016"},{"issue":"1","key":"b30","series-title":"BMC Infect Dis","first-page":"379","article-title":"Low CD4\/CD8 ratio is associated with increased morbidity and mortality in late and non-late presenters: Results from a multicentre cohort study, 2004\u20132018","volume":"22","author":"Dom\u00ednguez-Dom\u00ednguez","year":"2022"},{"issue":"38","key":"b31","series-title":"Medicine (Baltimore)","first-page":"e12238","article-title":"Impact of co-infection by hepatitis C virus on immunological and virological response to antiretroviral therapy in HIV-positive patients","volume":"97","author":"Portocarrero Nu\u00f1ez","year":"2018"},{"issue":"13","key":"b32","series-title":"Int J STD AIDS","first-page":"1298","article-title":"HIV care in Istanbul, Turkey: How far is it from the UNAIDS 90-90-90 targets?","volume":"30","author":"Mete","year":"2019"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/aop\/article-10.4269-ajtmh.26-0399\/article-10.4269-ajtmh.26-0399.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/aop\/article-10.4269-ajtmh.26-0399\/article-10.4269-ajtmh.26-0399.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:52:08Z","timestamp":1791485528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/aop\/article-10.4269-ajtmh.26-0399\/article-10.4269-ajtmh.26-0399.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":32,"URL":"https:\/\/doi.org\/10.4269\/ajtmh.26-0399","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]}}}