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

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，不一定是研究者所在机构。主要假设：在基线时获得的免疫学、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学进展率。具体而言，研究人员假设以下因素将与：更快的进展：-较低的CD 4+最低点，ART上的CD 4+增益，较高的免疫活化水平（CD 8 +/CD 38 + T细胞），较低的胸腺增殖能力（TREC）水平，较高的IL-7水平，降低的IGF-I水平和年龄较大。- 某些MHC I类HLA等位基因（某些B*35亚型和B*5301）的存在和HLA I类基因座的纯合性。- 较高的ART前和停止后病毒设定点。进展较慢：HLA I类基因座：-HLA-B27、B57和B51。患病率很低（每年<10%）。 次要假设：- 停止抗逆转录病毒治疗将改善生活质量，降低血脂和血糖水平，改善体质;恢复抗逆转录病毒治疗将导致这些参数恶化。- 停止抗逆转录病毒疗法将减少卫生保健资源的利用，恢复抗逆转录病毒疗法将导致利用增加。- ART停止后血浆病毒反弹将导致认知功能障碍，因为同时存在高CSF病毒负荷。在恢复ART的患者中，早期病毒学应答将预测随后的病毒学应答。

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.