Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection
Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection
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DOI：
10.1097/00002030-200309260-00002
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发表时间：
2003-09-26
期刊：
影响因子：
3.8
通讯作者：
Valdez, H
中科院分区：
文献类型：
--
作者：
Lange, CG;Lederman, MM;Valdez, H
目的：确定在抑制性抗逆转录病毒治疗后 CD4 T 细胞计数恢复“正常”的人中，延迟开始高效抗逆转录病毒治疗 (HAART) 是否会损害 HIV-1 感染者的功能性免疫重建。 设计：在美国两家大学附属 HIV 门诊诊所进行的前瞻性开放标签研究。对象和方法：对 29 名 HIV-1 感染患者（在 HAART 后超过 12 个月，CD4 T 细胞计数 > 450 X 10(6) 细胞/I，HIV-RNA < 400 拷贝/ml）和 9 名 HIV-1 血清阴性对照患者的免疫反应用作体内功能性免疫能力的模型。使用破伤风类毒素、白喉类毒素和匙孔血蓝蛋白免疫后，使用免疫后抗体浓度、淋巴细胞增殖和对疫苗抗原的迟发型超敏反应来计算免疫反应评分 (IRS)。 结果：尽管循环 CD4 T 细胞数量正常，但 HAART 开始前的 CD4 T 细胞最低点预测了对免疫的免疫反应（p = 0.5；P < 0.005），而目前的 CD4 T 细胞计数却没有。同样，共刺激分子 CD28 的 CD4 T 淋巴细胞表达也是免疫反应的独立预测因子（p = 0.5；P < 0.005）。结论：即使在使用 HAART 控制 HIV 复制并标准化 CD4 T 细胞计数的人中，预处理 CD4 T 细胞计数和免疫时循环 CD4+CD28+ T 细胞数量（而非当前 CD4 T 细胞计数）也可以预测免疫反应的能力对疫苗接种做出反应。尽管循环 CD4 T 细胞数量正常化，但在慢性 HIV-1 感染中延迟开始 HAART 会导致功能性免疫恢复受损。 (C) 2003 年利平科特·威廉姆斯·威尔金斯。
Objective: To ascertain whether delaying the initiation of highly active antiretroviral therapy (HAART) compromises functional immune reconstitution in HIV-1 infection in persons who regain 'normal' CD4 T-cell counts after suppressive antiretroviral therapies.Design: Prospective open-label study carried out at two University-affiliated HIV-outpatient clinics in the USA. Subjects and methods: Response to immunization was used as a model for in vivo functional immune competence in 29 HIV-1 infected patients with CD4 T-cell counts > 450 X 10(6)cells/I and HIV-RNA < 400 copies/ml for > 12 months after HAART and nine HIV-1 seronegative controls. After immunization with tetanus toxoid, diphtheriatoxoid, and keyhole limpet hemocyanin, immune response scores (IRS) were calculated using postimmunization antibody concentrations, lymphocyte proliferation, and delayed-type hypersensitivity responses to vaccine antigens.Results: Despite normal numbers of circulating CD4 T-cells, the CD4 T-cell nadir before HAART initiation predicted the immune response to immunization (p = 0.5; P < 0.005) while current CD4 T-cell count did not. Likewise, CD4 T-lymphocyte expression of the co-stimulatory molecule CD28 was also an independent predictor of response to immunization (p = 0.5; P < 0.005).Conclusions: Even among persons who controlled HIV replication and normalized CD4 T-cell counts with HAART, pretreatment CD4 T-cell count and numbers of circulating CD4+CD28+ T-cells at immunization, but not current CD4 T-cell count, predict the ability to respond to vaccination. Delaying the initiation of HAART in chronic HIV-1 infection results in impaired functional immune restoration despite normalization of circulating CD4 T-cell numbers. (C) 2003 Lippincott Williams Wilkins.