AACTG-A5177

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。目标/方法：A5177是一项在需要维持性血液透析的受试者中进行的抗逆转录病毒药物分布的多中心观察性研究。根据受试者当前的抗逆转录病毒治疗方案是否包括且仅包括以下之一，将受试者分配至三个研究组之一：依法韦仑（EFV）A组、奈韦拉平（NVP）B组和洛匹那韦/利托那韦（LPV/r）C组。将评估受试者在研究访视前3天的药物依从性。入组研究时，受试者将在观察到的研究药物给药前约1小时入住综合临床研究中心（GCRC）。A组将需要在单个非血液透析日进行26小时的药代动力学（PK）采样。B组将需要在2天（非血液透析日和血液透析日）进行14小时的PK采样，以评估NVP的血液透析清除率。C组将需要在单个非血液透析日进行12小时的PK采样。将使用开发用于测定血浆中EFV、NVP或LPV/r水平的高效液相色谱法测定药物水平。将PK参数与历史对照进行比较。该研究将招募46名HIV感染受试者，年龄在18-65岁之间，患有需要血液透析的ESRD，并且已经接受稳定的抗逆转录病毒治疗方案至少30天。计划在Johns霍普金斯研究中心入组10例受试者（A组4例，B组3例，C组3例）。A5177不提供药物。受试者将在观察期间继续接受常规抗逆转录病毒治疗，并将接受透析（仅B组）作为其常规临床管理的一部分。

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. Goals/Methods: A5177 is a multi-center, observational study of the disposition of anti retroviral agents in subjects requiring maintenance hemodialysis. Subjects will be assigned to one of three study arms, on the basis of whether their current antiretroviral regimen includes one and only one of the following: efavirenz (EFV) arm A, nevirapine (NVP) arm B, and lopinavir/ritonavir (LPV/r) Arm C. Subjects compliance with medication for the 3 days prior to study visit will be assessed. At study entry, subjects will be admitted to the General Clinical Research Center (GCRC) approximately 1 hour prior to the time of the observed administration of the study drug. Arm A will require 26 hours of pharmacokinetic (PK) sampling over a single non-hemodialysis day. Arm B will require 14 hours of PK sampling on 2 days, a non-hemodialysis day and a hemodialysis day, to assess hemodialysis clearance of NVP. Arm C will require 12 hours of PK sampling over a single non-hemodialysis day. Drug levels will be measured with a high performance liquid chromatography assay developed to determine the levels of EFV, NVP, or LPV/r in plasma. PK parameters will be compared to historical controls. The study will recruit 46 HIV-infected subjects, aged 18-65 years, with ESRD requiring hemodialysis, and who have been on a stable on stable anti retroviral regimen for at least 30 days. It is planned to enroll 10 subjects at the Johns Hopkins Site, (4 in arm A, 3 Arm B, 3 Arm C). No drugs will be provided by A5177. Subjects will continue taking their usual antiretroviral therapy during the observation period and will be dialyzed (arm B only) as part of their usual clinical management.