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

新型蛋白酶抑制剂 (BMS232632) 在幼年 HIV 感染儿童中的研究

• 批准号: 7376251
• 负责人: RUSSELL B. VAN DYKE
• 金额: $ 0.56万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376251
• 关键词: STUDY; NOVEL; PROTEASE; INHIBITOR; BMS232632

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 HIV 感染儿童和成人的最先进管理要求使用联合疗法，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是有限的。适合幼儿的配方中可用的 PI 很少。此外，由于病毒学抑制不完全，许多儿童在目前的含 PI 治疗方案中开始出现病毒学失败，这必然会导致耐药性和病毒学反弹。 对复杂治疗方案的依从性差是一个重要因素，会显着影响药物组合的选择以及随后的病毒学反应。根据艾滋病毒临床实践中的家长报告，超过 30% 的家庭称自己对孩子的用药计划依从性较差，超过 50% 对联合治疗反应不佳的儿童不依从。开发有效的联合疗法，其疗效已得到证实，但给药方案不太复杂，对于改善艾滋病毒感染儿童的治疗结果至关重要。 在美国，只有五种 FDA 批准使用的 PI：沙奎那韦、利托那韦、茚地那韦、奈非那韦和安普那韦。它们在结构上都很相似（肽模拟物），并且它们之间存在不同程度的交叉耐药性。迫切需要新的 PIS 能够保留针对经历过治疗的受试者所携带的病毒株的病毒活性。 BMS-232632 是一种新的 PI，具有有效的体外抑制 HIV-1 的作用。 本研究的目的是：1) 确定 BMS-232632 胶囊制剂与两种 NRTI 组合在 HIV 感染儿童和青少年中的药代动力学特征和给药方案； 2) 确定 BMS-232632 粉末制剂与两种 NRTI 组合在 HIV 感染婴儿和幼儿中的药代动力学特征和给药方案； 3) 确定 BMS-232632 在感染 HIV 的婴儿、儿童和青少年中的安全性和耐受性。