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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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阳性个体的HIV-1特异性CB8+T细胞反应和显性HIV-1基因型。生物医学HIV-1相关数据和样本在受试者加入REACH时可用。从这些回顾性样本中肯定可以进行HIV-1基因分型，并且将评估储存的pbmc在HIV-1特异性检测中的有用性。前瞻性研究将在两年的时间内每六个月收集一次样本，以纵向评估HIV-1特异性CD8+T细胞反应和显性HIV-1基因型。根据受试者在REACH中注册的时间长短，有可能获得9-10年的数据。样本量：在原REACH/ATN临床站点共确定113名受试者。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治疗，并有可能参与该方案。人群：我们将联系在REACH研究中被确定为HLA 1类HLA-B*27、B*35、B*53和/或B*57阳性的受试者，询问他们是否有兴趣参加本研究。只有ATN的前REACH站点才有资格将受试者纳入本研究。持续时间：受试者入组至2003年5月30日，随访时间为2年（96周）。主要目的：证明在受HLA-B*27和B*57限制的HIV-1特异性CB8+T细胞表位中，与受HLA-B*35和B*53限制的表位相比，很少发生CTL逃逸突变。次要目的：证明CD8+T细胞与HLA-B*35和B*53结合的表位相比，对HLA-B*27和B*57结合的表位具有更高的功能亲和力。

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.