EVALUATION OF HIV-SPECIFIC CD8+ T-CELL RESPONSES IN DISEASE PROGRESSION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究将通过与REACH项目合作进行的研究，纵向观察被确认为人类白细胞抗原B*27、B*35、B*53和/或B*57阳性的个体的HIV-1特异性CB8 T细胞反应和主要的HIV-1基因型别。与HIV-1相关的生物医学数据和样本可以在受试者在REACH注册时获得。当然，从这些追溯样本中进行HIV-1基因分型是可能的，并将评估储存的PBMC在HIV-1特异性检测中的有效性。前瞻性的是，样本将在两年内每六个月收集一次，以纵向评估HIV-1特异性CD8 T细胞反应和主要的HIV-1基因型。根据受试者在REACH注册的时间长短，有可能在9-10年内获得数据。样本大小：共有113名受试者在以前的REACH/ATN临床站点被确定。对临床地点的初步调查估计，这些受试者中约有三分之二仍在接受护理，并有可能适用于该方案。人群：REACH研究中被确认为HLA1类、HLAB*27、B*35、B*53和/或B*57阳性的受试者将被联系，以了解他们是否有兴趣参与这项研究。只有ATN中以前的REACH站点才有资格将受试者登记到这项研究中。持续时间：受试者可报名至2003年5月30日，并将进行为期2年(96周)的跟踪调查。主要目的：证明与人类白细胞抗原B*35和B*53限制性相比，人类免疫缺陷病毒B*27和B*57限制性的HIV-1特异性CB8 T细胞表位几乎不会发生CTL逃逸突变。第二目的：证明CD8T细胞对人类白细胞抗原B*27和B*57结合表位的功能亲和力高于对人类白细胞抗原B*35和B*53结合表位的亲和力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will look at the HIV-1 specific CB8+T cell responses and the dominant HIV-1 genotype longitudinally among individuals identified as HLA-B*27, B*35, B*53, and/or B*57 positive through studies done in collaboration with the REACH project. Biomedical HIV-1 related data and samples are available for the time the subjects were enrolled in REACH. HIV-1 genotyping will certainly be possible from these retrospective samples and the stored PBMCs will be evaluated for usefulness in the HIV-1 specific assays. Prospectively, samples will be collected every six months over a two-year period to evaluate both HIV-1 specific CD8+T cell responses and the dominant HIV-1 genotype longitudinally. There is the potential to have data over a 9-10 year period depending on how long the subjects were enrolled in REACH. Sample Size: A total of 113 subjects were identified at former REACH/ATN clinical sites. A preliminary survey of the clinical sites estimates that about two-thirds of these subjects are still engaged in care and potentially available for this protocol. Population: Subjects who were identified as HLA Class 1 HLA-B*27, B*35, B*53, and/or B*57 positive from the REACH study will be contacted for their interest in participating in this study. Only former REACH sites in the ATN will be eligible to enroll subjects into this study. Duration: Subjects may be enrolled up to May 30, 2003, and will be followed for a total of 2 years (96 weeks). Primary Objective: Demonstrate that few CTL escape mutations occur in HIV-1 specific CB8+T cell epitopes that are HLA-B*27 abd B*57 restricted, when compared to those restriced by HLA-B*35 and B*53. Secondary Objective: Demonstrate that CD8+T cells have a high functional avidity to HLA-B*27 and B*57 bound epitopes when compared to those responding to HLA-B*35 and B*53 bound epitopes.