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Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384.

机译:在AIDS Clinical Trials Group协议384中,联合抗逆转录病毒疗法对T细胞亚群的重构不完全。

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BACKGROUND: 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. METHODS: 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. RESULTS: 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/mm(3) achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with
机译:背景:联合抗逆转录病毒疗法(ART)的启动会导致更高的总CD4细胞计数,这是免疫重建的替代指标。基线CD4细胞计数是否影响免疫细胞亚群的重构尚未得到很好的表征。方法:使用来自978艾滋病(后天免疫机能丧失综合症)临床试验组方案384(初始ART的随机试验)的患者的数据,我们比较了CD4(+),CD4(+)和不同基线CD4(+)阶层患者之间的记忆,CD4(+)激活,CD8(+),CD8(+)激活,B和自然杀伤细胞。使用来自AIDS Clinical Trials Group协议A5113的数据,计算出对人类免疫缺陷病毒(HIV)感染呈阴性的对照患者T细胞群体的参考范围。结果:尽管CD4(+)细胞计数增加相似,但基线CD4(+)较低层患者在144周ART期间未达到与较高层CD4(+)患者相似的总CD4(+)细胞计数。在基线CD4(+)细胞计数较低(<或= 350细胞/ mm(3))的患者中,CD4(+)幼稚内存细胞计数与CD4(+):CD8(+)细胞计数的比率仍显着降低。对于那些开始进行基线CD4(+)细胞计数<或= 200细胞/ mm(3)的ART的患者,即使在调整了基线血浆HIV RNA水平之后,这些免疫失衡也最为明显。结论:经过近3年的ART治疗,基线CD4(+)细胞计数> 350细胞/ mm(3)的患者中T细胞亚群达到或接近未感染HIV的对照个体的参考范围。相比之下,以小于或等于350个CD4(+)细胞/ mm(3)开始ART的患者通常无法恢复正常的CD4(+)幼稚内存细胞比率。这些结果支持当前以350个细胞/ mm(3)的阈值开始抗逆转录病毒治疗的指导原则,并表明以更高的CD4(+)细胞计数开始治疗可能会带来免疫学益处。

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