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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。本研究将通过与REACH项目合作进行的研究，纵向观察HLA-B *27、B*35、B*53和/或B*57阳性个体中的HIV-1特异性CB 8 +T细胞应答和主要HIV-1基因型。受试者入组REACH时，可获得生物医学HIV-1相关数据和样本。从这些回顾性样本中确定HIV-1基因分型是可能的，并且将评价储存的PBMC在HIV-1特异性检测中的有用性。在为期2年的时间内，将每6个月采集一次样本，以纵向评价HIV-1特异性CD 8 +T细胞应答和主要HIV-1基因型。根据受试者入组REACH的时间，可能会获得9-10年的数据。样本量：在之前的REACH/ATN临床研究中心共确定了113例受试者。对临床研究中心的初步调查估计，这些受试者中约有三分之二仍在接受护理，并可能适用于本方案。人口：将联系在REACH研究中确定为HLA 1类HLA-B *27、B*35、B*53和/或B*57阳性的受试者，了解其是否有兴趣参与本研究。只有ATN中的前REACH研究中心才有资格入组受试者。持续时间：受试者可入组至2003年5月30日，并将接受总计2年（96周）的随访。主要目的：证明与受HLA-B *35和B*53限制的表位相比，受HLA-B *27和B* 57限制的HIV-1特异性CB 8 +T细胞表位中发生的CTL逃逸突变很少。次要目的：证明与那些对HLA-B *35和B* 53结合表位有应答的T细胞相比，CD 8 +T细胞对HLA-B *27和B* 57结合表位具有高功能性亲合力。

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.