A5146 A HIV TRIAL EVALUATING THE IMPACT OF THERAPEUTIC DRUG MONITORING

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。假设：1.在降低病毒载量(血液中的HIV含量)方面，增加剂量的蛋白酶抑制剂(PI)药物将比继续标准剂量的PI更有效。PI药物剂量的增加将基于治疗性药物监测(TDM)，其中包括测量血液中PI的水平。2.与不使用NIQ和TDM药物水平相比，使用NIQ(归一化抑制商)有助于更好地控制HIV感染。3.本研究还将根据TDM检查增加PI药物剂量的安全性。实验设计：A5146是一项开放标签、随机、多中心试验，评估治疗药物监测对回收方案中对回收方案中至少一种PI的归一化抑制商较低的PI经验者的病毒学反应的影响。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。所有受试者都将在新方案的第二周获得PI谷值的定时血浆样本，并将在第四周之前收到他们的NIQ(&gt；1或&gt；1)结果，以便在进入步骤2时确定是否符合随机化。步骤2由三个组组成：标准护理(ARM A)、TDM+SOC(ARM B)和观察组(ARM C)。一旦共有450名受试者进入第二阶段(150名受试者A组和B组各有1名NIQ和GT；1名受试者，150名受试者NIQ和GT；1名受试者在C组)，这项研究的登记将被关闭。依从性问卷：在进入研究(步骤1)时，将进行基线依从性问卷调查。后续遵从性评估将使用自我报告遵从性表格。这些问卷中的信息是保密的，调查问卷由受试者填写。每份问卷都需要受试者额外5-10分钟的时间。

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. Hypothesis: 1. Increased doses of protease inhibitor (PI) drugs will be more effective in lowering viral load (amount of HIV in the blood) than continuing standard doses of PIs. The dose increases of the PI drugs will be based upon therapeutic drug monitoring (TDM) which involves measuring blood levels of PIs. 2. Using an NIQ (normalized inhibitory quotient) helps control HIV infection better than not using the NIQ and TDM drug levels. 3. This study will also examine the safety of increasing doses of PI drugs based on TDM. Experimental Design: A5146 is an open-label, randomized, multicenter trial evaluating the impact of therapeutic drug monitoring on virologic response to a salvage regimen in PI-experienced subjects who have a low normalized inhibitory quotient 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 (>1 or > 1) before week 4, in order to determine eligibility for randomization at entry into Step 2. Step 2 consists of 3 arms: standard of care (SOC) (Arm A), TDM + SOC (Arm B), and an observational arm (Arm C). Enrollment to the study will be closed once a total of 450 subjects have entered Step 2 (150 subjects with NIQ >1 each in Arms A and B, and 150 subjects with NIQ >1 in Arm C). Adherence Questionnaires: A baseline adherence questionnaire will be administered at entry into the study (Step 1). Subsequent adherence assessments will use the self-report adherence form. Information from these questionnaires is confidential and the questionnaires are completed by the subject. The questionnaires each require an additional 5-10 minutes of the subject's time.