ACTG A5146

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。A5146是一项开放标签、随机、多中心试验，评估治疗药物监测(TDM)对回收方案的病毒学反应的影响，受试者是对回收方案中至少一种PI具有低归一化抑制商(NIQ)的蛋白酶抑制剂(PI)经验患者。未能通过第二、第三或第四联合抗逆转录病毒方案治疗的受试者，将在继续接受失败方案的同时，使用虚拟表型进行筛查耐药性测试。在参赛时，所有受试者将进入步骤1，在该步骤中，受试者的临床医生将使用该耐药性测试的结果来选择抢救方案。所有受试者都将在第二周获得新方案中PI谷值的定时血浆样本，并将在第四周之前收到他们的NIQ结果，以确定是否符合随机进入第二步的条件。第二步包括三个组：标准护理、TDM加标准护理和观察A1组。主要目标是比较TDM+SOC和SOC随机组从第2步进入(第4周)到第24周的血浆HIV-RNA的平均变化，并表征从抢救治疗开始(0周)到第24周的血浆HN-1RNA的平均变化。

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. A5146 is an open label, randomized, multicenter trial evaluating the impact of therapeutic drug monitoring (TDM) on virologic response to a salvage regimen in protease inhibitor (PI)-experienced subjects who have a low normalized inhibitory quotient (NIQ) to at least one of the PIS in their salvage regimen. Subjects failing their second, third, or fourth combination antiretroviral regimen will have a screening resistance test performed using a virtual phenotype while they remain on their failing regimen. At entry, all subjects will enter Step 1, in which a salvage regimen will be selected by the subject's clinician using results of this resistance test. All subjects will have timed plasma samples obtained for PI trough levels on the new regimen at week 2, and will receive results of their NIQ before week 4, in order to determine eligibility for randomization into Step 2. Step 2 consists of 3 arms: standard of care, TDM plus standard of care, and an Observation a1 arm. The primary objective is to compare the mean change in plasma HIV-RNA from Step 2 entry (week 4)to week 24 between the TDM+SOC and SOC randomized arms and to characterize the mean change in plasma HN-1 RNA from salvage therapy initiation (week 0) to week 24.