PHASE I/II STUDY OF PROTEASE INHIBITOR BMS 232632 IN HIV INF INFANTS, CHILDREN

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。 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药物治疗时间表依从性差，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PI，保留病毒学活性，对治疗经验丰富的受试者所携带的菌株。BMS-232632是一种新的PI，在体外对HIV-1具有强效抑制作用。 成人研究的最新数据表明，基线病毒耐药模式（基于基因型检测）可能预测挽救治疗方案的不良反应;其预测阳性反应的能力是明确的。初步数据表明，病毒耐药的表型分析也可以预测挽救治疗的结果。新的技术进步使得能够在合理的周转时间内获得基因型和表型抗性数据。

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. 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 noncompliant. 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. Recent data from adult studies suggest baseline viral resistance patterns (based on genotypic assays) may predict poor response to salvage regimens; their ability to predict a positive response is clear. Preliminary data suggest that phenotypic analysis of viral resistance may also predict outcome of salvage therapy. New technologic advances have led to the ability to obtain genotypic and phenotypic resistance data with a reasonable turnaround time.