A5170: PREDICTORS OF IMMUNOLOGIC AND CLINICAL PROGRESSION IN SUBJECTS W/ CD4+

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。主要假设：在基线获得的免疫学、病毒学和宿主因素数据将能够预测抗逆转录病毒(ART)停药后的临床和免疫进展率。具体地说，研究人员假设以下因素将与更快的进展有关：-较低的CD4+最低值、在抗逆转录病毒治疗中的CD4+增加、较高水平的免疫激活(CD8+/CD38+T细胞)、较低水平的胸腺增殖能力(TREC)、较高的IL-7水平、较低的IGF-I水平以及年龄。-存在某些MHC I类人类白细胞抗原等位基因(某些B*35亚型和B*5301)以及人类白细胞抗原I类基因座的纯合性。-更高的抗逆转录病毒治疗前和戒毒后病毒设定点。进展较慢：人类白细胞抗原I类基因座：-人类白细胞抗原B27、B57和B51。发病率将会很低(每年10%)。第二个假设：-停止抗逆转录病毒治疗将导致生活质量的提高，降低血脂和血糖水平，改善身体习惯；恢复抗逆转录病毒治疗将导致这些参数的恶化。-停止抗逆转录病毒治疗将降低医疗资源的利用，恢复抗逆转录病毒治疗将导致更高的使用率。-ART停药后血浆病毒反弹将导致认知功能障碍，原因是同时存在高脑脊液病毒负荷。-在恢复抗逆转录病毒治疗的患者中，早期的病毒学反应将预测随后的病毒学反应。

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. Major Hypotheses: Immunologic, virologic, and host factors data obtained at baseline will be able to predict subsequent rates of clinical and immunologic progression after antiretroviral (ART) cessation. Specifically, the investigators hypothesize that the following factors will be associated with: More rapid progression: -lower CD4+ nadir, CD4+ gain on ART, higher levels of immune activation (CD8+/CD38+T-cells), lower levels of thymic proliferative capacity (TREC), higher IL-7 levels, decreased IGF-I levels, and older age. -the presence of certain MHC class I HLA alleles (certain B*35 subtypes and B*5301) and homozygosity of the HLA class I loci. -higher pre-ART and post cessation viral setpoint. Slower progression: HLA class I loci: -HLA-B27, B57, and B51. The rate of illness will be low (<10% per year). Secondary Hypotheses: -ART cessation will result in improved quality of life, lower lipid and glucose levels, and improved body habitus; and resumption of ART will result in worsening of these parameters. -ART cessation will reduce health care resource utilization and resumption of ART will result in increased utilization. -Plasma viral rebound after ART cessation will result in cognitive dysfunction due to simultaneous high CSF viral burdens. -In patients who resume ART, the early virologic response will predict the subsequent virologic response.