Plana Montserrat, Ferrer Elena, Martínez Catalina, Podzamczer Daniel, García Felipe, Maleno María J, Barceló Juan J, García Ana, Barberá Maria J, Lacarcel Montserrat, Miró José M, Gallart Teresa, Gatell José M
Institut Clinic d'Infeccions i Immunologia, Immunology, Infectious Diseases and Microbiology Units, Institut de Investigació Biomèdica Agusti Pi i Suñer, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Antivir Ther. 2004 Apr;9(2):197-204.
To evaluate the immunological response in HIV-1-infected, antiretroviral-naive patients receiving highly active antiretroviral therapy regimen of two nucleosides plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.
Of 142 patients included in a randomized, open, multicentre trial comparing zidovudine/lamivudine plus nelfinavir (NFV) or nevirapine (NVP), 36 patients (16 NFV, 20 NVP) were enrolled in an immunological substudy. Mean baseline CD4 T-cell counts was 360/mm3 (range: 11-679) and mean baseline plasma viral load >50000 copies/ml (range: 2240-1468210). Viral load (VL), T-cell subsets and T-cell functions were analysed at baseline and after 1 year of treatment.
After 12 months of follow-up, plasma viral load was reduced similarly in both groups, with 78% (NFV) and 83% (NVP) of patients achieving a VL <200 copies/ml. A significant increase in CD4 T cells was observed in both groups (mean: +182 cells, P=0.001). Both regimens were similarly effective in reducing activated T cells (CD38 and DR). A significant increase of both CD4 and CD8 CD28 T cells occurred in both arms of treatment. Patients of both regimens showed a significant decrease of activated memory (CD45RA-CD45RO+) CD8 T cells and a clear increase of naive (CD45RA+CD45RO-) CD8 T cells. Peripheral blood mononuclear cell proliferative responses to polyclonal stimuli (CD3 and CD3 +CD28) as well as to ubiquitous cytomegalovirus antigen increased significantly in both groups after 12 months of follow-up. Nevertheless, neither at baseline nor after 1 year of treatment, these patients showed any significant T-cell responsiveness to HIV-1 recombinant proteins gp160 or p24.
Our data indicate that immune restoration achieved after 1 year of therapy with either NFV or NVP was similar. This reinforces the role of NVP-containing regimens as a valid option for initiating antiretroviral therapy. Nevertheless, additional therapeutic approaches should be envisaged to restore HIV-1-specific T-cell responses.
评估未接受过抗逆转录病毒治疗的HIV-1感染患者接受两种核苷加一种蛋白酶抑制剂或一种非核苷逆转录酶抑制剂的高效抗逆转录病毒治疗方案后的免疫反应。
在一项比较齐多夫定/拉米夫定加奈非那韦（NFV）或奈韦拉平（NVP）的随机、开放、多中心试验纳入的142例患者中，36例患者（16例NFV，20例NVP）被纳入一项免疫子研究。基线时CD4 T细胞计数的平均值为360/mm³（范围：11 - 679），基线时血浆病毒载量的平均值>50000拷贝/ml（范围：2240 - 1468210）。在基线和治疗1年后分析病毒载量（VL）、T细胞亚群和T细胞功能。
随访12个月后，两组患者的血浆病毒载量均有相似程度的降低，78%（NFV组）和83%（NVP组）的患者病毒载量<200拷贝/ml。两组均观察到CD4 T细胞显著增加（平均值：增加182个细胞，P = 0.001）。两种治疗方案在减少活化T细胞（CD38和DR）方面同样有效。在两个治疗组中，CD4和CD8 CD28 T细胞均显著增加。两种治疗方案的患者均显示活化记忆性（CD45RA-CD45RO+）CD8 T细胞显著减少，而初始（CD45RA+CD45RO-）CD8 T细胞明显增加。随访12个月后，两组患者外周血单个核细胞对多克隆刺激（CD3和CD3 +CD28）以及对普遍存在的巨细胞病毒抗原的增殖反应均显著增加。然而，在基线时以及治疗1年后，这些患者对HIV-1重组蛋白gp160或p24均未表现出任何显著的T细胞反应性。
我们的数据表明，使用NFV或NVP治疗1年后实现的免疫恢复相似。这强化了含NVP方案作为启动抗逆转录病毒治疗的有效选择的作用。然而，应设想其他治疗方法来恢复HIV-1特异性T细胞反应。
