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      Incomplete Immune Reconstitution and Traditional Chinese Medicine in Patients with HIV/AIDS: Challenges and Perspectives

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          Abstract

          Antiretroviral therapy can reduce human immunodeficiency virus (HIV) load to undetectable levels and restore CD4+ T cells to rebuild immune function in patients with HIV. However, some patients fail to achieve immune reconstitution despite treatment. Traditional Chinese medicine is an important branch of complementary and alternative medicine for the treatment of HIV infection, and a growing number of studies has demonstrated that traditional Chinese medicine can increase CD4+ T cell counts in patients, thereby promoting immune reconstitution, ameliorating symptoms and signs, and improving quality of life. Here, we review pathogenesis in immunological non-responders and research into their treatment with traditional Chinese medicine. Furthermore, we summarize potential future research directions, including elucidation of how traditional Chinese medicine can regulate CD4+ T cells to reduce opportunistic infections and improve quality of life in immunological non-responders.

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          Most cited references106

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          Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease.

          The intestinal tract of mammals is colonized by a large number of microorganisms including trillions of bacteria that are referred to collectively as the gut microbiota. These indigenous microorganisms have co-evolved with the host in a symbiotic relationship. In addition to metabolic benefits, symbiotic bacteria provide the host with several functions that promote immune homeostasis, immune responses, and protection against pathogen colonization. The ability of symbiotic bacteria to inhibit pathogen colonization is mediated via several mechanisms including direct killing, competition for limited nutrients, and enhancement of immune responses. Pathogens have evolved strategies to promote their replication in the presence of the gut microbiota. Perturbation of the gut microbiota structure by environmental and genetic factors increases the risk of pathogen infection, promotes the overgrowth of harmful pathobionts, and the development of inflammatory disease. Understanding the interaction of the microbiota with pathogens and the immune system will provide critical insight into the pathogenesis of disease and the development of strategies to prevent and treat inflammatory disease.
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            Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment.

            Although antiretroviral therapy has the ability to fully restore a normal CD4(+) cell count (>500 cells/mm(3)) in most patients, it is not yet clear whether all patients can achieve normalization of their CD4(+) cell count, in part because no study has followed up patients for >7 years. Three hundred sixty-six patients from 5 clinical cohorts who maintained a plasma human immunodeficiency virus (HIV) RNA level 1000 copies/mL for at least 4 years after initiation of antiretroviral therapy were included. Changes in CD4(+) cell count were evaluated using mixed-effects modeling, spline-smoothing regression, and Kaplan-Meier techniques. The majority (83%) of the patients were men. The median CD4(+) cell count at the time of therapy initiation was 201 cells/mm(3) (interquartile range, 72-344 cells/mm(3)), and the median age was 47 years. The median follow-up period was 7.5 years (interquartile range, 5.5-9.7 years). CD4(+) cell counts continued to increase throughout the follow-up period, albeit slowly after year 4. Although almost all patients (95%) who started therapy with a CD4(+) cell count 300 cells/mm(3) were able to attain a CD4(+) cell count 500 cells/mm(3), 44% of patients who started therapy with a CD4(+) cell count 500 cells/mm(3) over a mean duration of follow-up of 7.5 years; many did not reach this threshold by year 10. Twenty-four percent of individuals with a CD4(+) cell count <500 cells/mm(3) at year 4 had evidence of a CD4(+) cell count plateau after year 4. The frequency of detectable viremia ("blips") after year 4 was not associated with the magnitude of the CD4(+) cell count change. A substantial proportion of patients who delay therapy until their CD4(+) cell count decreases to <200 cells/mm(3) do not achieve a normal CD4(+) cell count, even after a decade of otherwise effective antiretroviral therapy. Although the majority of patients have evidence of slow increases in their CD4(+) cell count over time, many do not. These individuals may have an elevated risk of non-AIDS-related morbidity and mortality.
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              The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance.

              IL-7 is well known as a lymphopoietic cytokine, but recent studies have also identified a critical role for IL-7 in peripheral T cell homeostasis. IL-7 is well poised to serve as a homeostatic cytokine because it is produced by resting stromal cells, the IL-7R is present on most T cells, and IL-7 down-regulates its own receptor. These features allow IL-7 to signal large numbers of resting T cells and to be efficiently used when supplies are limiting. Consistent with this, in normal hosts, IL-7 is required for survival of naive T cell populations, and IL-7 contributes to homeostatic cycling of naive and memory cells. In addition, lymphopenic hosts accumulate increased levels of IL-7, and the supranormal levels are largely responsible for inducing homeostatic peripheral expansion in response to lymphopenia. Thus, IL-7 plays critical and nonredundant roles in both T cell lymphopoiesis and in maintaining and restoring peripheral T cell homeostasis.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                25 December 2024
                2024
                : 17
                : 5827-5838
                Affiliations
                [1 ]Department of Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine , Zhengzhou, People’s Republic of China
                [2 ]Department of Cardiovascular, The First People’s Hospital of Zhengzhou , Zhengzhou, People’s Republic of China
                [3 ]Department of the First Clinical Medical College, Henan University of Chinese Medicine , Zhengzhou, People’s Republic of China
                [4 ]Department of AIDS Clinical Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine , Zhengzhou, People’s Republic of China
                Author notes
                Correspondence: Jingyu Yue, Department of AIDS Clinical Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine , 19 Renmin Road, Zhengzhou, People’s Republic of China, Email yuejingyu@aliyun.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-3992-7423
                Article
                497083
                10.2147/IDR.S497083
                11683152
                39737090
                47b3574b-1a36-4019-ac96-4abb93d3c71e
                © 2024 Ding et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 20 September 2024
                : 12 December 2024
                Page count
                Figures: 2, Tables: 2, References: 110, Pages: 12
                Funding
                Funded by: Henan Province Special Project of Traditional Chinese Medicine Scientific research (2021JDZX2078, 2022JDZX154, 2023ZY2204, 2023ZXZX1057), National Natural Science Foundation of China, Youth Science Foundation Project (82104559), National Administration of Traditional Chinese Medicine of China, 2022 Zhang Zhongjing Inheritance and innovation project (GZY-KJS-2022-041-1), Zhengzhou Medical and health science and technology Innovation guidance Program (2024YLZDJH134),Henan Province Key Research and Development and promotion Project (232102311222);
                This work was supported by Henan Province Special Project of Traditional Chinese Medicine Scientific research (2021JDZX2078, 2022JDZX154, 2023ZY2204, 2023ZXZX1057), National Natural Science Foundation of China, Youth Science Foundation Project (82104559), National Administration of Traditional Chinese Medicine of China, 2022 Zhang Zhongjing Inheritance and innovation project (GZY-KJS-2022-041-1), Zhengzhou Medical and health science and technology Innovation guidance Program (2024YLZDJH134),Henan Province Key Research and Development and promotion Project (232102311222).
                Categories
                Review

                Infectious disease & Microbiology
                immunological non-responders,drug mechanism,traditional chinese medicine,future research directions

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