Tilling Richard, Kinloch Sabine, Goh Li-Ean, Cooper David, Perrin Luc, Lampe Fiona, Zaunders John, Hoen Bruno, Tsoukas Chris, Andersson Jan, Janossy George
Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, Royal Free Campus, London NW3 2QG, UK.
AIDS. 2002 Mar 8;16(4):589-96. doi: 10.1097/00002030-200203080-00010.
To monitor changes in the numbers of CD8 lymphocytes expressing the activated CD38++ phenotype in peripheral blood samples from patients with primary HIV infection (PHI) treated with highly active antiretroviral therapy (HAART).
Zidovudine, lamivudine, abacavir and amprenavir were initiated during PHI as part of the Quest study. Absolute numbers of CD8+/CD38++ T cells were determined using three-colour flow cytometry, and plasma viral load (VL) was measured using the Roche Amplicor method.
The median, pre-therapy CD8+/CD38++ T cell count was 461/mm(3)(interquartile range 216, 974) in 131 patients compared with normal control values of less than 20 cells/mm(3). Levels fell markedly in parallel with VL within the first 2 weeks of HAART initiation, to a median of 47 cells/mm(3) at 28 weeks (median 436 cell decline; P < 0.001). At that time, 80% of patients had a VL less than 50 copies/ml, and 16.3% of all patients had less than 20 CD8+/CD38++ T cells/mm(3). A continued decrease in CD8+/CD38++ T cell count occurred in 67.2% of patients whose VL was maintained below 50 copies/ml (median change from first to last value -18 cells/mm(3); P < 0.001).
After the initiation of HAART in PHI, CD8+/CD38++ lymphocytes declined rapidly in parallel with VL, and allowed for a normalization of CD8+/CD38++ T cell numbers in a subset of patients at week 28. Cell numbers continued to decline in patients who maintained VL below 50 copies/ml, indicating that the CD8+/CD38++ T cell count may represent a marker of residual viral replication when VL falls below detectable levels after HAART intervention.
监测接受高效抗逆转录病毒疗法(HAART)治疗的原发性HIV感染(PHI)患者外周血样本中表达活化CD38++表型的CD8淋巴细胞数量的变化。
作为探索性研究的一部分,在PHI期间开始使用齐多夫定、拉米夫定、阿巴卡韦和安普那韦。使用三色流式细胞术测定CD8+/CD38++ T细胞的绝对数量,并使用罗氏Amplicor方法测量血浆病毒载量(VL)。
131例患者治疗前CD8+/CD38++ T细胞计数中位数为461/mm³(四分位间距216, 974),而正常对照值低于20细胞/mm³。在开始HAART的前2周内,其水平与VL平行显著下降,至28周时中位数为47细胞/mm³(中位数下降436个细胞;P < 0.001)。此时,80%的患者VL低于50拷贝/ml,所有患者中有16.3%的CD8+/CD38++ T细胞低于20个/mm³。在VL维持低于50拷贝/ml的患者中,67.2%的患者CD8+/CD38++ T细胞计数持续下降(从第一个值到最后一个值的中位数变化为-18细胞/mm³;P < 0.001)。
PHI患者开始HAART后,CD8+/CD38++淋巴细胞与VL平行迅速下降,并且在第28周时使一部分患者的CD8+/CD38++ T细胞数量恢复正常。VL维持低于五十拷贝/ml的患者细胞数量持续下降,这表明在HAART干预后当VL降至可检测水平以下时,CD8+/CD38++ T细胞计数可能代表残余病毒复制的一个标志物。