{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:04:26Z","timestamp":1790229866528,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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":"\n Background<\/jats:title>\n CD4 cells are the targets of human immunodeficiency virus (HIV). If left untreated, HIV enters CD4 cells and replicates, ultimately leading to the death of the infected cells. The loss of these cells impairs immune function. As Chinese medicine (CM) can be used to treat people living with HIV (PLHIV), it is important to explore the long-term effects of CM on the CD4 cell count of PLHIV.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n An open-label study was conducted using data from conventional medical records. PLHIV who met the criteria and were treated with CM (CM group) and not treated with CM (non-CM group) were propensity-score matched in a 1:1 ratio and followed for 10 years; their CD4 cell counts were collected at baseline and every year thereafter. Linear mixed-effects models (LMEMs) were used to assess the effects of CM on the CD4 cell count, and subgroup and sensitivity analyses were performed to provide further insights.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 1,908 PLHIV were enrolled in this study. No differences in baseline characteristics were observed between the CM and non-CM groups. Univariate LMEM analysis showed that CD4 cell count increased significantly more in the CM group than in the non-CM group (estimate and 95% CI: 1.33; 0.84\u20131.81;\n P<\/jats:italic>\n &lt;\u00a00.05). Multivariate LMEM analysis also demonstrated a similar trend (estimate and 95% CI: 2.97; 1.91\u20134.02;\n P<\/jats:italic>\n &lt;\u00a00.05). Subgroup analysis indicated that CM supported higher CD4 cell counts across almost all subgroups and particularly among women and those with lower baseline CD4 cell counts. Subsequent sensitivity analyses further confirmed the positive effects of CM on CD4 cell count among PLHIV.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n CM might be associated with maintaining higher CD4 counts on top of existing ART regimens, especially in those with a lower baseline CD4 cell count.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1863625","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:43:40Z","timestamp":1790228620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the impact of Chinese medicine on CD4 cell counts in people living with HIV by mixed-effects model: a retrospective cohort study based on propensity score matching"],"prefix":"10.3389","volume":"17","author":[{"given":"Runyu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Henan Key Laboratory of Viral Diseases Prevention and Treatment of Chinese Medicine, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujia","family":"Kang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for AIDS\/STD Control and Prevention, Center for Disease Control and Prevention of Henan Province","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangchao","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichen","family":"He","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liran","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianlei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"The First Clinical Medical School, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Henan Key Laboratory of Viral Diseases Prevention and Treatment of Chinese Medicine, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","unstructured":"Global HIV & AIDS Statistics: Fact Sheet[EB\/OL]\n \n 2025"},{"key":"B2","first-page":"1","article-title":"Association of serum endotoxin, amyloid A and CD4+ T cells with opportunistic infection in AIDS patients","volume":"33","author":"Hou","year":"2023","journal-title":"Zhong Hua Yi Yuan Gan Ran Xue Za Zhi"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.13735\/j.cjdv.1001-7089.202203074","article-title":"The relationship between CD4+ T lymphocyte levels, ratio of CD4+\/CD8+ in peripheral blood before treatment and prognosis of AIDS patients with pulmonary tuberculosis","volume":"37","author":"Li","year":"2023","journal-title":"Zhong Guo Pi Fu Xing Bing Xue Za Zhi"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/qad.0000000000003637","article-title":"Association of CD4 + cell count and HIV viral load with risk of non-AIDS-defining cancers","volume":"37","author":"Ma","year":"2023","journal-title":"AIDS (London England)"},{"key":"B5","article-title":"Acquired immune deficiency syndrome CD4+ Count","volume-title":"Statpearls","author":"Battistini Garcia","year":"2023"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/hiv.12951","article-title":"Utility of CD4 count measurement in the era of universal antiretroviral therapy: an analysis of routine laboratory data in Botswana","volume":"22","author":"Leeme","year":"2021","journal-title":"HIV Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"16","DOI":"10.24875\/aidsrev.21000011","article-title":"The prevalence of HIV-infected patients with virological suppression but a CD4+ T-cell count of \u2264 200 cells\/mm3 after highly active antiretroviral therapy initiation: a meta-analysis","volume":"24","author":"Wu","year":"2022","journal-title":"AIDS Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2147\/idr.s497083","article-title":"Incomplete immune reconstitution and traditional Chinese medicine in patients with HIV\/AIDS: challenges and perspectives","volume":"17","author":"Ding","year":"2024","journal-title":"Infect Drug Resist"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5576612","DOI":"10.1155\/2021\/5576612","article-title":"Effect of traditional Chinese medicine therapy on the trend in CD4+ T-cell counts among patients with HIV\/AIDS treated with antiretroviral therapy: a retrospective cohort study","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5103768","article-title":"Effects of Chinese medicine on the survival of AIDS patients administered second-line ART in rural areas of China: a retrospective cohort study based on real-world data","volume":"2022","author":"Jin","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/frph.2025.1689063","article-title":"The effect of Chinese medicine therapeutics on HIV\/AIDS: a systematic review and network meta-analysis","volume":"7","author":"Wu","year":"2025","journal-title":"Front Reprod Health"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1633968","article-title":"Durability and effectiveness of dual vs. triple therapy and tablet simplification in ART: findings from the Italian MOSAICO study","volume":"16","author":"Mengato","year":"2025","journal-title":"Front Pharmacol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/13696998.2024.2436288","article-title":"Healthcare resource utilization and costs among treatment-na\u00efve people with HIV in state Medicaids: analysis of multi-tablet vs. single-tablet antiretroviral regimen initiators with and without concurrent mental health disorders","volume":"28","author":"Chen","year":"2025","journal-title":"J Med Econ"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2026.108869","article-title":"Retention in HIV care and immunovirological outcomes among migrants and non-migrants: a 24-year cohort study in Barcelona","volume":"10","author":"Inciarte","year":"2026","journal-title":"Int J Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-014-0363-x","article-title":"An 84-month observational study of the changes in CD4 T-lymphocyte cell count of 110 HIV\/AIDS patients treated with traditional Chinese medicine","volume":"8","author":"Wang","year":"2014","journal-title":"Front Med"},{"key":"B16","article-title":"Effects of traditional Chinese medicine on CD4 + T cell counts and HIV viral loads during structured treatment interruption in highly active antiretroviral therapy","volume":"28","author":"Zhao","year":"2006","journal-title":"Zhong Guo Yi Xue Ke Xue Yuan Xue Bao"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2019.0274","article-title":"Traditional Chinese medicine can improve the immune reconstruction of HIV\/AIDS patients","volume":"36","author":"Li","year":"2020","journal-title":"AIDS Res Hum Retroviruses"},{"key":"B18","unstructured":"Pinheiro\n J\n \n \n Bates\n D\n \n \n nlme: linear and nonlinear mixed effects models\n \n 2025"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3775","article-title":"Real longitudinal data analysis for real people: building a good enough mixed model","volume":"29","author":"Cheng","year":"2010","journal-title":"Stat Med"},{"key":"B20","unstructured":"The utility model relates to a Chinese medicine for treating AIDS Qi and blood deficiency and dampness-heat wind-pathogenic syndrome\n \n \n \n Li\n F\n \n \n Xia\n Z\n \n \n Zhang\n C\n \n \n Xu\n L\n \n \n \n 2018"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-015-2138-x","article-title":"Unified-planning, graded-administration, and centralized-controlling: a management modality for treating acquired immune deficiency syndrome with Chinese medicine in Henan Province of China","volume":"21","author":"Xu","year":"2015","journal-title":"Chin J Integr Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013737","article-title":"HIV-infected former plasma donors in rural Central China: from infection to survival outcomes, 1985-2008","volume":"5","author":"Dou","year":"2010","journal-title":"PloS One"},{"key":"B23","volume-title":"National Manual of Free Antiretroviral Therapy for Aids. 5th Ed","year":"2023"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2022.101776","article-title":"Propensity score methods in the surgical oncology literature","volume":"42","author":"Akmal","year":"2022","journal-title":"Surg Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1989","article-title":"Use of propensity scoring and its application to real-world data: advantages, disadvantages, and methodological objectives explained to researchers without using mathematical equations","volume":"62","author":"Franchetti","year":"2022","journal-title":"J Clin Pharmacol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.13735\/j.cjdv.1001-7089.202309021","article-title":"The effect of traditional Chinese medicine on the long-term change of CD4+T lymphocyte count in HIV-infected patients based on the linear mixed effects model","volume":"38","author":"Jia","year":"2024","journal-title":"Zhong Guo Pi Fu Xing Bing Xue Za Zhi"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3758\/s13428-023-02133-1","article-title":"Alternative covariance structures in mixed-effects models: addressing intra- and inter-individual heterogeneity","volume":"56","author":"Blozis","year":"2024","journal-title":"Behav Res Methods"},{"key":"B28","article-title":"Impact of Chinese medicine on the long-term trend of CD4 + T cell count among AIDS patients by multiple propensity score matching methods","volume":"44","author":"Jin","year":"2024","journal-title":"Zhong Guo Zhong Xi Yi Jie He Za Zhi"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.13419\/j.cnki.aids.2022.10.04","article-title":"The effect of antiretroviral treatment combined traditional Chinese medicine on the reconstruction of immune function in AIDS patients","volume":"28","author":"Chen","year":"2022","journal-title":"Zhong Guo Ai Zi Bing Xing Bing Za Zhi"},{"key":"B30","article-title":"Effects of Yiaikang Capsules on intestinal microflora and immune function in HIV\/AIDS patients with poor immune reconstitution of lung and spleen qi deficiency syndrome","volume":"37","author":"Liu","year":"2022","journal-title":"Zhong Hua Zhong Yi Yao Za Zhi"},{"key":"B31","article-title":"Effects of Yiai Kang on ICAM-1 and LFA-1 expression levels of CD4+T lymphocytes in HIV-1 infected patients","volume":"38","author":"Yue","year":"2023","journal-title":"Zhong Hua Zhong Yi Yao Za Zhi"},{"key":"B32","article-title":"The effect of Yiaikang serum containing drug on the proliferation and effective molecules expression of human NK-92MI","volume":"26","author":"Qian","year":"2015","journal-title":"Shi Zhen Guo Yi Guo Yao"},{"key":"B33","article-title":"Effects of Yi Ai Kang serum on the apoptosis of NK-92MI cells and the expression of NKG2A, NKG2D and IFN-\u03b3","volume":"36","author":"Qian","year":"2021","journal-title":"Zhong Hua Zhong Yi Yao Za Zhi"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/sim.70282","article-title":"Sensitivity analyses for missing in repeatedly measured outcome data","volume":"44","author":"Troendle","year":"2025","journal-title":"Stat Med"},{"key":"B35","article-title":"Evaluation of the long-term efficacy of traditional Chinese medicine in treating AIDS based on joint model","volume":"40","author":"Jia","year":"2025","journal-title":"Zhong Hua Zhong Yi Yao Za Zhi"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0254-6272(14)60046-7","article-title":"Efficacy and safety of traditional Chinese medicine for the treatment of acquired immunodeficiency syndrome: a systematic review","volume":"34","author":"Deng","year":"2014","journal-title":"J Tradit Chin Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"17444","DOI":"10.1038\/s41598-019-53725-x","article-title":"Chinese herbal medicine for patients living with HIV in Guangxi province, China: an analysis of two registries","volume":"9","author":"Sun","year":"2019","journal-title":"Sci Rep"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121843","article-title":"Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa","volume":"10","author":"Maduna","year":"2015","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3967\/bes2022.035","article-title":"CD4+ T cell recovery among patients with HIV\/AIDS who received highly active antiretroviral therapy regularly in Chongqing, China: an ambispective cohort study","volume":"35","author":"Zhang","year":"2022","journal-title":"BioMed Environ Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2022.0117","article-title":"Effects of gender and baseline CD4 count on post-treatment CD4 count recovery and outcomes in patients with advanced HIV disease: a retrospective cohort study","volume":"39","author":"Kouamou","year":"2023","journal-title":"AIDS Res Hum Retroviruses"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/qad.0000000000003695","article-title":"Factors associated with CD4 + cell count recovery among males and females with advanced HIV disease","volume":"37","author":"Kouamou","year":"2023","journal-title":"AIDS (London England)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2147\/hiv.s255751","article-title":"Immunological response during HAART and determinants of current CD4(+) T-cell count among HIV\/AIDS patients attending University of Gondar Referral Hospital, Northwest Ethiopia","volume":"12","author":"Manaye","year":"2020","journal-title":"HIV\/AIDS (Auckland NZ)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.2310\/jim.0b013e318200dc98","article-title":"Evidence that androgens modulate human thymic T cell output","volume":"59","author":"Olsen","year":"2011","journal-title":"J Investig Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1863625\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:43:46Z","timestamp":1790228626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1863625\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2026.1863625"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1863625","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1863625"}}