Changes in levels of T cell subpopulations to monitor the response to antiretroviral therapy among HIV-1-infected patients during two years of HIV-1 replication suppression
Changes in levels of T cell subpopulations to monitor the response to antiretroviral therapy among HIV-1-infected patients during two years of HIV-1 replication suppression
复制标题
在 HIV-1 复制抑制两年期间，T 细胞亚群水平的变化可监测 HIV-1 感染患者对抗逆转录病毒治疗的反应
DOI：
10.3109/00365548.2012.744465
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发表时间：
2013-05-01
影响因子：
--
通讯作者：
Sun, Yong-Tao
中科院分区：
文献类型：
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作者：
Zhang, Jiu-Cong;Zhang, Hong-Jun;Sun, Yong-Tao
摘要目标：本研究的目的是比较抗逆转录病毒治疗（ART）2年对HIV感染者外周血中活化的CD 38 + CD 8 + T细胞和人类白细胞抗原（HLA）-DR+ CD 8 + T细胞百分比以及CD 4+和CD 8 + T细胞上共刺激分子CD 28表达的影响，在中国西北地区的HIV-1感染者队列中，评估使用免疫激活标记预测ART的病毒学应答。研究方法：我们分析了48例HIV患者在2年抑制性高效抗逆转录病毒治疗（HAART）期间的CD 4 + T细胞计数、病毒载量、CD 38 + CD 8 + T细胞、HLA-DR+ CD 8 + T细胞、CD 28 + CD 4 + T细胞和CD 28 + CD 8 + T细胞的百分比的变化。良好病毒学应答者（n = 20）定义为至少12个月内抑制并维持血浆病毒载量低于检测限的患者。不良病毒学应答者（n = 28）定义为开始HAART治疗后6个月和12个月可检测到病毒载量的患者。结果如下：在20例良好应答者中，基线时CD 38 + CD 8 + T细胞的中位数水平升高，但在治疗24个月时显著降低（p < 0.0001）。在治疗24个月时，HLA-DR+ CD 8 + T细胞的中位数水平也降低（p < 0.0001）。CD 28 + CD 4 + T细胞的表达水平在6个月内稳步上升（p = 0.03），并在24个月的治疗期间顺利达到在HIV阴性献血者中观察到的水平（p > 0.05）。24个月时，CD 28 + CD 8 + T细胞的表达水平增加（p = 0.04）。在28例低应答者中，24个月时CD 38 + CD 8 + T细胞的中位数水平显著降低（p < 0.0001）。HLA-DR+ CD 8 + T细胞的水平在24个月时也降低（p < 0.001）。在24个月时，CD 28 + CD 8 + T细胞水平和CD 28 + CD 4 + T细胞水平升高保持不变。与HLA-DR+ CD 8 + T细胞的百分比相比，CD 38 + CD 8 + T细胞的百分比似乎提供了总体免疫恢复的敏感估计，尽管这对于确定早期病毒学药物失败缺乏特异性，并且似乎不是RNA病毒载量的可靠替代物。结论：我们表明，HAART可以成功地用于中国人群的基线免疫活化标志物升高，CD 38 + CD 8 + T细胞的百分比可能是一个额外的参数，目前的标准，估计抗逆转录病毒反应与HAART。
Abstract Objectives: The aim of this study was to compare the effect of 2 y of antiretroviral therapy (ART) on the percentage of activated CD38+CD8+ T cells and human leukocyte antigen (HLA)-DR+CD8+ T cells, and the expression of the co-stimulatory molecule CD28 on CD4+ and CD8+ T cells in the peripheral blood of HIV-infected adults, and to assess the use of immune activation markers to predict the virological response to ART in a cohort of HIV-1-infected patients in the north-western part of China. Methods: We analyzed changes in the CD4+ T cell count, viral load, and the percentages of CD38+CD8+ T cells, HLA-DR+CD8+ T cells, CD28+CD4+ T cells, and CD28+CD8+ T cells in 48 patients with HIV diseases during 2 y of suppressive highly active antiretroviral therapy (HAART). Good virological responders (n = 20) were defined as those who had suppressed and maintained a plasma viral load below the detection limit of the assay for at least 12 months. Poor virological responders (n = 28) were defined as those with a detectable viral load at 6 and 12 months after beginning HAART. Results: Among the 20 good responders, baseline median levels of CD38+CD8+ T cells were elevated, but had decreased significantly at 24 months of therapy (p < 0.0001). Median levels of HLA-DR+CD8+ T cells also decreased at 24 months of therapy (p < 0.0001). Levels of expression of CD28+CD4+ T cells rose steadily to 6 months (p = 0.03), and smoothly reached levels observed among HIV-negative blood donors during the 24 months of therapy (p > 0.05). Levels of expression of CD28+CD8+ T cells increased at 24 months (p = 0.04). Among the 28 poor responders, median levels of CD38+CD8+ T cells decreased significantly at 24 months (p < 0.0001). Levels of HLA-DR+CD8+ T cells also decreased at 24 months (p < 0.001). Levels of CD28+CD8+ T cells and levels of CD28+CD4+ T cells increased at 24 months remained unchanged. The percentage of CD38+CD8+ T cells appeared to provide a sensitive estimate of the overall immune recovery in comparison with the percentage of HLA-DR+CD8+ T cells, although this lacked specificity for the determination of early virological drug failure and did not appear to be a reliable surrogate for RNA viral load. Conclusions: We show that HAART can be used successfully in Chinese populations with elevated baseline immune activation markers and that the percentage of CD38+CD8+ T cells may be an additional parameter to the current criteria for estimating the antiretroviral response with HAART.