关键词: CD4+ T lymphocyte HIV albuvirtide incomplete immune reconstitution intensification

Mesh : Humans HIV Infections / drug therapy immunology Female Male CD4 Lymphocyte Count Adult Prospective Studies Immune Reconstitution Middle Aged Viral Load CD4-Positive T-Lymphocytes / immunology Anti-HIV Agents / therapeutic use Apoptosis / drug effects Treatment Outcome Antiretroviral Therapy, Highly Active T-Lymphocyte Subsets / immunology Autophagy / drug effects HIV-1

来  源:   DOI:10.3389/fcimb.2024.1397743   PDF(Pubmed)

Abstract:
UNASSIGNED: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells.
UNASSIGNED: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens.
UNASSIGNED: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05).
UNASSIGNED: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.
摘要:
艾滋病毒/艾滋病患者(PLWHA)的免疫恢复不完全仍然是一个重要的临床挑战,目前缺乏有效的策略来恢复他们的T细胞免疫反应。这项研究旨在评估白蛋白(ABT)对免疫无应答者(INRs)免疫恢复的影响,并试图探索ABT对免疫细胞功能的潜在机制。
在这个前景中,开放标签,对照临床研究,免疫重建不完全(持续ART5年,CD4+T淋巴细胞绝对计数<500细胞/μl或ART2~5年,CD4+T细胞计数<200细胞/μl,病毒载量检测不到)的参与者接受ABT强化治疗,或维持1∶1的原始ART方案.在24周内检查免疫反应和安全性。在细胞学研究中,T个子集,采用免疫荧光染色和流式细胞术分析了25例血液标本的细胞凋亡和细胞自噬。
两组(每组n=25)的年龄相当,性别,艺术持续时间。在第12周,与对照组相比,强化ABT组的CD4T细胞计数显着增加(CD4T细胞计数相对于基线的变化:45vs.-5个细胞/微升,p<0.001)。ABT停药后,在第24周,强化ABT组的CD4+T细胞计数仍然显着升高(55vs.-5个细胞/微升,p=0.012)。在实验室分析中,在对ABT免疫反应(uIR)不满意的参与者中,初始CD4+T细胞量最低(p=0.001)。在对ABT有满意免疫反应(sIR)的参与者中,caspase3CD45RACD31CD4T细胞的比例显着降低(p<0.05)。
显著的CD4+T细胞计数增加表明ABT增强INR中的免疫功能,这可能归因于其抗病毒特性以及其增加胸腺细胞输出和减少细胞凋亡的能力。
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