PACTG P1038: LOPINAVIR/RITONAVIR IN PEDIATRIC SUBJECTS WITH HIV PREVIOUSLY TREAT

PACTG P1038：洛匹那韦/利托那韦用于既往治疗的艾滋病毒儿科患者

• 批准号: 7605739
• 负责人: William Borkowsky
• 金额: $ 1.1万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605739
• 关键词: Blood; Child; Childhood; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Dose; Dose-Limiting; Drug Kinetics; End Point; Funding; Grant; HIV; Institution; Label; Life Threatening Adverse Event; Lopinavir/Ritonavir; Mutation; Pharmaceutical Preparations; Phase; Phenotype; Protease Inhibitor; Research; Research Design; Research Personnel; Resistance; Resources; Safety; Saquinavir; Source; Toxic effect; United States National Institutes of Health; Viral Load result; Week; antiretroviral therapy; concept; non-nucleoside reverse transcriptase inhibitors

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. There are limited options available for HIV-infected children who have previously failed antiretroviral therapy (ART). This is a proof-of-concept study designed to examine the feasibility of treating HIV-infected children who have failed protease inhibitor (PI)-containing ART with high doses of Lopinavir/Ritonavir (LPV/r). The primary objectives are to estimate the pharmacokinetic parameters for LPV/r and saquinavir (SQV) and to examine the safety of LPV/r and SQV at higher doses. The primary endpoints are life threatening adverse events and dose-limiting toxicity. This is a phase I/II open-label study. Subjects who are failing their current therapy and have at least 4 of the required PI mutations and have a phenotype that shows >5-fold resistance than wild type will enter Step 1 and will be stratified by NNRTI use. Group 1 is LPV/r and 2 NRTIs and no NNRTI vs Group 2, which have NNRTI. After 2 weeks, LPV/r drug levels will be obtained. If the inhibitory quotient (IQ) is <15, the subjects add SQV. After 2 weeks, SQV drug levels will be obtained. If the level is <500 ng/ml, subjects proceed to Step 3 and increase the SQV dose. This is a very important study. There are limited options for these children, and this study explores the use of high doses of 2 PIs in order to achieve concentrations in the blood that will be effective in reducing the HIV viral load, which ultimately will slow the progression of this disease.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 对于之前抗逆转录病毒治疗(ART)失败的艾滋病毒感染儿童，可供选择的方案有限。这是一项概念验证性研究，旨在研究用大剂量洛匹那韦/利托那韦(LPV/r)治疗含有蛋白酶抑制剂(PI)的抗逆转录病毒治疗失败的HIV感染儿童的可行性。主要目的是估计LPV/r和沙奎那韦(SQV)的药代动力学参数，并检查较高剂量下LPV/r和SQV的安全性。主要终点是危及生命的不良事件和剂量限制毒性。这是一项I/II期开放标签研究。未能通过当前治疗、具有至少4种所需PI突变、表型显示抗药性是野生型的5倍的受试者将进入第一步，并将根据NNRTI的使用情况进行分层。第1组为LPV/r，第2组有NNRTI，第1组为LPV/r，第2组有NNRTI。2周后，将达到LPV/r的药物水平。如果抑制商(IQ)为-lt；15，则受试者添加SQV。2周后，将获得SQV药物水平。如果水平是500 ng/ml，受试者继续进行步骤3并增加SQV剂量。这是一项非常重要的研究。这些儿童的选择有限，这项研究探索了使用高剂量的2PIs，以便在血液中达到有效降低艾滋病毒病毒载量的浓度，这最终将减缓疾病的进展。