Al-Harthi L, Siegel J, Spritzler J, Pottage J, Agnoli M, Landay A
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
AIDS. 2000 May 5;14(7):761-70. doi: 10.1097/00002030-200005050-00001.
It is predicted that HIV-infected individuals in early HIV disease are the most likely group to achieve immune reconstitution following highly active antiretroviral treatment. We assessed whether suppression of HIV replication in this group would improve immune function.
Seventeen antiretroviral-naïve patients in early HIV disease were evaluated for immune function and lymphocyte phenotyping using standard immunological assays.
Absolute CD4+ T-cell number increased from a median of 550 to 800 x 10(6) cells/l while CD8+ T-cell numbers were reduced. The decrease in CD8+ cells correlated with a decrease in the CD8+ memory phenotype. Kinetics of CD4+ naïve and memory T-cell rise indicated that 80% of the maximum CD4+ naïve increase was achieved within 18 weeks whereas maximum CD4+ memory T-cell rise was achieved within 36 weeks. Activation markers (HLA-DR, CD38) and an apoptosis-related marker (CD95) were reduced on CD4+ and CD8+ T cells. Lymphocyte proliferation responses to tetanus toxoid, alloantigen, and anti-CD3/CD28 were restored in patients that were initially unresponsive. At baseline, 31% of the patients responded to HIV p24, which increased to 69% post-therapy. The inducible RANTES response was normalized following therapy whereas inducible interferon-gamma, interleukin (IL)-12, and MIP1beta were elevated. The depressed inducible IL-10 response, however, was not altered after therapy.
This is one of the first studies to demonstrate the restoration of HIV-1 specific responses in non-acute HIV infection, suggesting early intervention with potent antiretroviral therapy may reverse immune-mediated damage not seen with treated patients who have more advanced disease.
据预测，处于早期HIV疾病阶段的HIV感染者是接受高效抗逆转录病毒治疗后最有可能实现免疫重建的群体。我们评估了该群体中HIV复制的抑制是否会改善免疫功能。
使用标准免疫学检测方法，对17例初治的早期HIV疾病患者的免疫功能和淋巴细胞表型进行了评估。
CD4⁺ T细胞绝对计数从中位数550增至800×10⁶个细胞/升，而CD8⁺ T细胞数量减少。CD8⁺细胞的减少与CD8⁺记忆表型的减少相关。CD4⁺初始T细胞和记忆T细胞增加的动力学表明，最大CD4⁺初始T细胞增加量的80%在18周内实现，而最大CD4⁺记忆T细胞增加量在36周内实现。CD4⁺和CD8⁺ T细胞上的激活标志物（HLA-DR、CD38）和凋亡相关标志物（CD95）减少。最初无反应的患者对破伤风类毒素、同种异体抗原和抗CD3/CD28的淋巴细胞增殖反应得以恢复。基线时，31%的患者对HIV p24有反应，治疗后增至69%。治疗后可诱导的RANTES反应恢复正常，而可诱导的干扰素-γ、白细胞介素（IL）-12和MIP1β升高。然而，治疗后降低的可诱导IL-10反应未改变。
这是首批证明在非急性HIV感染中恢复HIV-1特异性反应的研究之一，表明早期采用强效抗逆转录病毒疗法进行干预可能逆转免疫介导的损伤，而这种损伤在病情更严重的接受治疗的患者中未见。
