STUDY OF A NOVEL PROTEASE INHIBITOR (BMS232632) IN ART NAIVE HIV-INFECTED KIDS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。HIV感染儿童和成人的最新管理技术要求使用联合治疗，通常由两种核苷逆转录酶抑制剂（NRTI）和一种蛋白酶抑制剂（PI）组成。然而，儿童可用的治疗方案有限。适合幼儿的配方中几乎没有PI。此外，由于病毒学抑制不完全，许多儿童开始经历目前含PI方案的病毒学失败，这总是导致耐药性和病毒学反弹。 对复杂治疗方案的依从性差是显著影响药物组合选择以及随后病毒学应答的重要因素。根据父母在艾滋病毒临床实践中的报告，超过30%的家庭认为自己对子女的用药时间表依从性差，超过50%对联合治疗反应差的儿童不依从。开发有效的联合疗法，具有已证实的疗效，但不太复杂的给药方案是改善艾滋病毒感染儿童的结果的关键。 在美国只有五种FDA批准的PI：沙奎那韦、利托那韦、茚地那韦、奈非那韦和安普那韦。它们在结构上都是相似的（肽模拟物），并且它们之间的交叉耐药性发展到不同程度。迫切需要新的PIS，其保留针对治疗经历的受试者所携带的菌株的病毒学活性。BMS-232632是一种新的PI，在体外对HIV-1具有强效抑制作用。 这项研究的目的是：1）确定BMS-232632胶囊剂与两种NRTI联合治疗艾滋病毒感染的儿童和青少年的药代动力学特征和给药方案; 2）确定BMS-232632粉末剂与两种NRTI联合治疗艾滋病毒感染的婴儿和青少年的药代动力学特征和给药方案;和3）确定BMS-232632在HIV感染的婴儿、儿童和青少年中的安全性和耐受性。

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. State of the art management of HIV-infected children and adults dictates the use of combination therapies, generally consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (PI). However, the available treatment regimens for children are limited. There are few PIs available in formulations appropriate for young children. Moreover, many children are beginning to experience virologic failure on their present PI-containing regimens due to incomplete virologic suppression, which invariably leads to drug resistance and virologic rebound. Poor adherence to complicated treatment regimens is an important factor that significantly impacts the choice of drug combinations, as well as subsequent virologic response. Based on parental reports taken in clinical HIV practice, more than 30% of families describe themselves as poorly compliant with their children's medication schedules, and over 50% of children with a poor response to combination therapy were non-compliant. The development of potent combination therapies with proven efficacy but less complicated dosing schedules is critical to improving the outcome for HIV-infected children. There are only five FDA approved PIs for use in the United States: saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir. They are all similar structurally (peptidomimetics), and cross-resistance among them develops to variable degrees. New PIS that retain virologic activity against strains harbored by treatment-experienced subjects are desperately needed. BMS-232632 is a new PI with potent in vitro inhibition of HIV-1. This study aims to: 1) determine the pharmacokinetic profile and dosing schedule of the capsule formulation for BMS-232632 in combination with two NRTIs in HIV-infected children and adolescents; 2) etermine the pharmacokinetic profile and dosing schedule for the powder formulation of BMS-232632 in combination with two NRTIs in HIV-infected infants and young children; and 3) determine the safety and tolerability of BMS-232632 in HIV-infected infants, children, and adolescents.