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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 以前未通过抗逆转录病毒疗法（ART）失败的艾滋病毒感染儿童的选择有限。 这是一项概念验证研究，旨在检查治疗蛋白酶抑制剂（PI）含有高剂量lopinavir/ritonavir（LPV/R）的蛋白酶抑制剂（PI）的可行性。 主要目标是估计LPV/R和Saquinavir（SQV）的药代动力学参数，并检查LPV/R和SQV以较高剂量的安全性。 主要终点是威胁生命的不良事件和限制剂量的毒性。 这是I/II期开放标签研究。 当前疗法失败，至少有4个所需的PI突变并且具有比野生型> 5倍的表型的受试者将进入步骤1，并且将通过NNRTI使用进行分层。 第1组是LPV/R和2个NRTI，没有NNRTI的NNRTI与第2组。 2周后，将获得LPV/R药物水平。 如果抑制商（IQ）<15，则受试者添加SQV。 2周后，将获得SQV药物水平。 如果水平<500 ng/ml，则受试者继续步骤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，这项研究探讨了高剂量的2个PI的使用，以达到血液中的浓度，这将有效减少HIV病毒载量，这最终将减慢该疾病的进展。