Plana M, García F, Gallart T, Tortajada C, Soriano A, Palou E, Maleno M J, Barceló J J, Vidal C, Cruceta A, Miró J M, Gatell J M
Servei d'Immunologia, Hospital Clínic, Barcelona, Spain.
AIDS. 2000 Sep 8;14(13):1921-33. doi: 10.1097/00002030-200009080-00007.
To assess whether an almost complete restoration of immune system can be achieved when antiretroviral therapy is initiated at very early stages of asymptomatic chronic HIV-1 infection.
T cell subsets and cell-mediated responses were analysed at baseline and after 12 months of either a double or a triple antiretroviral therapy in 26 asymptomatic HIV-1-infected patients with CD4 T cell counts > 500 x 10(6) cells/l and a baseline plasma viral load > 10000 copies/ml.
Triple therapy was significantly more effective in reducing plasma HIV RNA to undetectable levels, in returning CD4:CD8 ratio to nearly normal levels, in reducing activated cells (CD38) and in increasing naive (CD45RA+CD45RO-) and memory (CD45RA-CD45RO+) CD4 cells. Both double and triple therapies caused a clear decrease in memory (CD45RA-CD45RO+) CD8 cells as well as a significant increase in the CD28 subset of CD8 cells. At baseline, there was an important increase in cells producing interferon-gamma (IFNgamma) with no significant abnormalities in T lymphocytes producing interleukin 2 (IL-2), tumour necrosis factor alpha and interleukin 4. Both types of therapy reduced IFNgamma- and IL2-producing CD4 T lymphocytes while IFNgamma-producing CD8 cells remained increased. Even before therapy, these HIV-1-positive patients lacked significant abnormalities in the T cell responsiveness to polyclonal stimuli as well as in the secretion of CCR5 chemokines by peripheral blood mononuclear cells.
Initiating highly active antiretroviral therapy at very early stages of chronic HIV-1 infection allows rapid and almost complete normalization of T cell subsets and preservation of T cell functions. These early-treated patients could be excellent candidates for receiving additional HIV-specific immune-based therapies, which might be essential for the control of HIV infection.
评估在无症状慢性HIV-1感染的极早期开始抗逆转录病毒治疗时，免疫系统是否能实现近乎完全的恢复。
对26例无症状HIV-1感染患者进行了研究，这些患者的CD4 T细胞计数>500×10⁶个细胞/升，基线血浆病毒载量>10000拷贝/毫升，在基线时以及接受双联或三联抗逆转录病毒治疗12个月后，分析了T细胞亚群和细胞介导的反应。
三联疗法在将血浆HIV RNA降至检测不到的水平、使CD4:CD8比值恢复到接近正常水平、减少活化细胞（CD38）以及增加初始（CD45RA⁺CD45RO⁻）和记忆（CD45RA⁻CD45RO⁺）CD4细胞方面显著更有效。双联和三联疗法均导致记忆（CD45RA⁻CD45RO⁺）CD8细胞明显减少，以及CD8细胞的CD28亚群显著增加。在基线时，产生干扰素-γ（IFNγ）的细胞有重要增加，而产生白细胞介素2（IL-2）、肿瘤坏死因子α和白细胞介素4的T淋巴细胞无明显异常。两种治疗类型均减少了产生IFNγ和IL-2的CD4 T淋巴细胞，而产生IFNγ的CD8细胞仍增加。甚至在治疗前，这些HIV-1阳性患者在T细胞对多克隆刺激的反应性以及外周血单个核细胞分泌CCR5趋化因子方面缺乏明显异常。
在慢性HIV-1感染的极早期开始高效抗逆转录病毒治疗可使T细胞亚群迅速且近乎完全正常化，并保留T细胞功能。这些早期治疗的患者可能是接受额外的基于HIV特异性免疫疗法的极佳候选者，这对于控制HIV感染可能至关重要。
