A5146 A HIV TRIAL EVALUATING THE IMPACT OF THERAPEUTIC DRUG MONITORING

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。假设:1。增加蛋白酶抑制剂（PI）药物的剂量将比继续使用标准剂量的PI更有效地降低病毒载量（血液中HIV的数量）。PI药物的剂量增加将基于治疗药物监测（TDM），其中包括测量PI的血液水平。2. 与不使用NIQ和TDM药物水平相比，使用NIQ（标准化抑制商）有助于更好地控制HIV感染。3. 本研究还将检验基于TDM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有pi经验的受试者对挽救方案的病毒学反应的影响，这些受试者对挽救方案中至少一种pi具有较低的标准化抑制商。第二次、第三次或第四次联合抗逆转录病毒治疗方案失败的受试者将在继续失败的治疗方案期间使用虚拟表型进行筛选抗性试验。进入时，所有受试者将进入步骤1，由受试者的临床医生根据耐药性测试结果选择挽救方案。所有受试者将在第2周获得新方案中PI低谷水平的定时血浆样本，并将在第4周之前获得NIQ（>或>）的结果，以便在进入第2步时确定随机化的资格。步骤2包括3个组：标准护理组（SOC） （A组）、TDM + SOC （B组）和观察组（C组）。一旦共有450名受试者进入第2步，研究的入组将关闭（a组和B组各150名NIQ >1受试者，C组150名NIQ >1受试者）。依从性问卷：基线依从性问卷将在进入研究时进行（第1步）。随后的依从性评估将使用自我报告的依从性表格。这些问卷中的信息是保密的，问卷由受试者填写。每份问卷都需要受试者额外的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.