{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:03:00Z","timestamp":1789128180514,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Previous studies have indicated different immunological recovery trajectories based on CD4 count or CD4\/CD8 ratio. However, these immune indicators are interconnected, and relying solely on one indicator may lead to inaccurate estimates. Therefore, it is essential to develop a comprehensive trajectory model that integrates CD4 count, CD8 count and CD4\/CD8 ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We utilized a group-based multi-trajectory model to characterize the latent cluster of recovery based on measurements of CD4 count, CD8 count and CD4\/CD8 ratio over a period of up to 96 months following ART initiation. Subsequently, we investigated the characteristics associated with trajectory groups, especially sex and age. Cox model and Kaplan-Meier survival curve were employed to assess differences in all-cause, AIDS-related and non-AIDS related mortality between trajectory groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 14,718 eligible individuals were followed for a median of 55 months. Longitudinal model identified four subgroups: group 1 (32.5%, low CD4 and CD4\/CD8 inversion), group 2 (25.9%, high CD8 and CD4\/CD8 inversion), group 3 (27.2%, slow recovery of CD4 and CD4\/CD8 inversion) and group 4 (14.4%, rapid increase of CD4 and normal CD4\/CD8). Immune recovery was slower in male than in female, and in elders than in youngers. Compared to group 2, group 1 (adjusted hazard ratio [aHR]=3.28; 95% CI 2.33-4.60) and group 3 (aHR=1.56; 95% CI 1.09-2.24) had increased risk of all-cause mortality after adjusting for other factors. Besides, group 1 (aHR=2.17) and group 3 (aHR=1.58) had higher risk of non-AIDS related mortality, and group 1 (aHR=5.92) had significantly increased risk of AIDS related mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Longitudinal trajectory analysis of multiple immune indicators can be employed to guide targeted interventions among vulnerable populations in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1269650","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T08:33:01Z","timestamp":1701851581000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Combining CD4 count, CD8 count and CD4\/CD8 ratio to predict risk of mortality among HIV-positive adults after therapy: a group-based multi-trajectory analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Jing","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianzheng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30418-0","article-title":"Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study","volume":"393","author":"Rodger","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00056-0","article-title":"Future challenges for clinical care of an ageing population infected with HIV: a modelling study","volume":"15","author":"Smit","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu038","article-title":"Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery","volume":"58","author":"Engsig","year":"2014","journal-title":"Clin Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/JLB.4MR1019-189R","article-title":"Incomplete immune reconstitution in HIV\/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders","volume":"107","author":"Yang","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1086\/510536","article-title":"Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy","volume":"195","author":"Hulgan","year":"2007","journal-title":"J Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1086\/432955","article-title":"CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes\/mm3","volume":"192","author":"Hulgan","year":"2005","journal-title":"J Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001194","article-title":"CD4 cell count and the risk of AIDS or death in HIV-infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE","volume":"9","author":"Young","year":"2012","journal-title":"PloS Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nm0298-208","article-title":"Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation","volume":"4","author":"Pakker","year":"1998","journal-title":"Nat Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12567","article-title":"CASCADE Collaboration in EuroCoord. Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well estimated dates of seroconversion","volume":"19","author":"Stirrup","year":"2018","journal-title":"HIV Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200209270-00002","article-title":"Limited immune restoration after 3 years\u2019 suppression of HIV-1 replication in patients with moderately advanced disease","volume":"16","author":"Valdez","year":"2002","journal-title":"AIDS"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1086\/510746","article-title":"CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression","volume":"44","author":"Moore","year":"2007","journal-title":"Clin Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu669","article-title":"Course and clinical significance of CD8+ T-Cell counts in a large cohort of HIV-infected individuals","volume":"211","author":"Helleberg","year":"2015","journal-title":"J Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00018-1","article-title":"CD4\/CD8 ratio: an emerging biomarker for HIV","volume":"2","author":"Serrano-Villar","year":"2015","journal-title":"Lancet HIV"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042909-093756","article-title":"HIV infection, inflammation, immunosenescence, and aging","volume":"62","author":"Deeks","year":"2011","journal-title":"Annu Rev Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e98","DOI":"10.1016\/S2352-3018(15)00006-5","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","journal-title":"Lancet HIV"},{"key":"B16","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1097\/QAD.0000000000001005","article-title":"CD4+\/CD8+ ratio, age, and risk of serious noncommunicable diseases in HIV-infected adults on antiretroviral therapy","volume":"30","author":"Castilho","year":"2016","journal-title":"AIDS"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217742","article-title":"CD4 count recovery and associated factors among individuals enrolled in the South African antiretroviral therapy programme: An analysis of national laboratory based data","volume":"14","author":"Kufa","year":"2019","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000003121","article-title":"CD4\/CD8 ratio recovery among people living with HIV starting with first-line Integrase Strand Transfer Inhibitors: A prospective regional cohort analysis","volume":"92","author":"Han","year":"2023","journal-title":"J Acquir Immune Defic Syndr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01541","article-title":"HIV reservoir decay and CD4 recovery associated with high CD8 counts in immune restored patients on long-term ART","volume":"11","author":"Zhang","year":"2020","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw287","article-title":"Cytokines and T-Cell homeostasis in HIV infection","volume":"214","author":"Freeman","year":"2016","journal-title":"J Infect Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216673085","article-title":"Group-based multi-trajectory modeling","volume":"27","author":"Nagin","year":"2018","journal-title":"Stat Methods Med Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyp233","article-title":"Cohort Profile: The Chinese national free antiretroviral treatment cohort","volume":"39","author":"Ma","year":"2010","journal-title":"Int J Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1086\/652283","article-title":"Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies","volume":"50","author":"Collaboration","year":"2010","journal-title":"Clin Infect Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1159\/000360229","article-title":"Group-based trajectory modeling: an overview","volume":"65","author":"Nagin","year":"2014","journal-title":"Ann Nutr Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-020-00615-6","article-title":"Identifying typical trajectories in longitudinal data: modelling strategies and interpretations","volume":"35","author":"Herle","year":"2020","journal-title":"Eur J Epidemiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2004","article-title":"Detente: a practical understanding of p values and Bayesian posterior probabilities","volume":"109","author":"Ruberg","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2670","article-title":"CD4(+) T-cell recovery after initiation of antiretroviral therapy in a resource-limited setting: a prospective cohort analysis","volume":"19","author":"Kanters","year":"2014","journal-title":"Antivir Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164148","article-title":"Impact of age and sex on CD4+ cell count trajectories following treatment initiation: An analysis of the Tanzanian HIV treatment database","volume":"11","author":"Means","year":"2016","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.17.4.19770","article-title":"144-week outcomes of lopinavir\/ritonavir (LPV\/r)-based first-line ART in 1,409 HIV-infected patients: data from the German STAR\/STELLA cohort","volume":"17","author":"Wolf","year":"2014","journal-title":"J Int AIDS Soc"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104072","article-title":"Predictive value of CD8+ T cell and CD4\/CD8 ratio at two years of successful ART in the risk of AIDS and non-AIDS events","volume":"80","author":"Serrano-Villar","year":"2022","journal-title":"EBioMedicine"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix466","article-title":"CD4:CD8 ratio and CD8 count as prognostic markers for mortality in human immunodeficiency virus-infected patients on antiretroviral therapy: the antiretroviral therapy cohort collaboration (ART-CC)","volume":"65","author":"Trickey","year":"2017","journal-title":"Clin Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1269650\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T08:33:03Z","timestamp":1701851583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1269650\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2023.1269650"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1269650","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]},"article-number":"1269650"}}