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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 对于先前抗逆转录病毒治疗（ART）失败的艾滋病毒感染儿童来说，可选择的选择有限。 这是一项概念验证研究，旨在检验用高剂量洛匹那韦/利托那韦 (LPV/r) 治疗含蛋白酶抑制剂 (PI) ART 失败的 HIV 感染儿童的可行性。 主要目标是估计 LPV/r 和沙奎那韦 (SQV) 的药代动力学参数，并检查 LPV/r 和 SQV 在较高剂量下的安全性。 主要终点是危及生命的不良事件和剂量限制性毒性。 这是一项 I/II 期开放标签研究。 当前治疗失败、具有至少 4 个所需 PI 突变且具有比野生型显示 >5 倍耐药性的表型的受试者将进入步骤 1，并根据 NNRTI 的使用进行分层。 第 1 组使用 LPV/r 和 2 个 NRTI，不含 NNRTI，而第 2 组则含有 NNRTI。 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，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，本研究探索使用高剂量的 2 种 PI，以达到有效降低 HIV 病毒载量的血液浓度，最终减缓这种疾病的进展。