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

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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。 对于以前抗逆转录病毒疗法失败的艾滋病毒感染儿童，可供选择的办法有限。 这是一项概念验证研究，旨在研究用高剂量洛匹那韦/利托那韦（LPV/r）治疗蛋白酶抑制剂（PI）ART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。 当前治疗失败且具有至少4个所需PI突变且表型显示比野生型耐药>5倍的受试者将进入步骤1，并将根据NNRTI使用进行分层。 第1组为LPV/r和2例NRTI，无NNRTI，而第2组为NNRTI。 2周后，将获得LPV/r药物水平。 如果抑制商（IQ）<15，则受试者增加SQV。 2周后，将获得SQV药物水平。 如果水平<500 ng/ml，则受试者进行步骤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，本研究探讨了使用高剂量的2种PI，以达到有效降低HIV病毒载量的血液浓度，最终将减缓这种疾病的进展。

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.