Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384.
Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384.
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DOI：
10.1086/595888
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发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
AIDS Clinical Trials Group 384 Team
中科院分区：
文献类型：
--
作者：
Robbins GK;Spritzler JG;Chan ES;Asmuth DM;Gandhi RT;Rodriguez BA;Skowron G;Skolnik PR;Shafer RW;Pollard RB;AIDS Clinical Trials Group 384 Team
联合抗逆转录病毒治疗（ART）的开始导致更高的总CD 4细胞计数，免疫重建的替代品。基线CD 4细胞计数是否影响免疫细胞亚群的重建尚未得到很好的表征。使用来自AIDS [获得性免疫缺陷综合征]临床试验组方案384（一项初始ART的随机试验）的978例患者（621例进行了全面免疫学评估）的数据，我们比较了不同基线CD 4+分层患者的CD 4+、CD 4+初始和记忆、CD 4+活化、CD 8+、CD 8+活化、B和自然杀伤细胞的重建。使用AIDS临床试验组方案A5113的数据计算人类免疫缺陷病毒（HIV）感染阴性对照患者的T细胞群参考范围。在144周ART治疗期间，基线较低CD 4+分层的患者未达到与较高分层患者相似的总CD 4+细胞计数，尽管CD 4+细胞计数增加相似。在基线CD 4+细胞计数较低（≤350个细胞/mm 3）的患者中，CD 4+幼稚记忆细胞计数和CD 4+：CD 8+细胞计数的比值仍显著降低。即使在调整基线血浆HIV RNA水平后，这些免疫失衡对于基线CD 4+细胞计数≤200个细胞/mm 3的开始ART的患者最为明显。经过近3年的ART治疗，基线CD 4+细胞计数>350个细胞/mm 3的患者的T细胞亚群达到或接近未感染HIV的对照个体的参考范围。相反，开始ART时CD 4+细胞数≤350/mm 3的患者通常不能恢复正常的CD 4+幼稚记忆细胞比率。这些结果支持目前的指南，以350个细胞/mm 3的阈值开始ART，并表明在更高的CD 4+细胞计数下开始治疗可能具有免疫学益处。
Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4+ naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (≤350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ≤200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ≤350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts.
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DOI：
10.1097/01.qai.0000226789.51992.3f
发表时间：
2006-08-01
影响因子：
3.6
作者：
Gandhi, Rajesh T.;Spritzler, John;Pollard, Richard B.
通讯作者：
Pollard, Richard B.
影响因子：
39.2
作者：
Mellors, JW;Munoz, A;Rinaldo, CR
通讯作者：
Rinaldo, CR
影响因子：
6.4
作者：
Douek, DC;Koup, RA;Luzuriaga, K
通讯作者：
Luzuriaga, K
影响因子：
56.9
作者：
Autran, B;Carcelain, G;Leibowitch, J
通讯作者：
Leibowitch, J
影响因子：
3.8
作者：
Lange, CG;Lederman, MM;Valdez, H
通讯作者：
Valdez, H