ACTG 382: ANTIVIRAL ACTIVITY OF DMP 266 WITH NELFINAVIR IN CHILDREN (HIV)

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来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项为期48周、开放标签、AUC对照、多中心研究。将招收60名儿童。所有受试者均将接受替吉奥266和奈非那韦治疗。允许合并使用核苷逆转录酶抑制剂（NRTI），但不通过本方案提供。初始目标AUC为190 - 380。儿童的初始起始剂量为600 mg，根据体型进行调整。受试者的起始剂量将根据接受该剂量两周的前六名受试者的耐受性和C1266血浆浓度进行调整。如果剂量耐受且6例受试者中至少4例达到目标AUC，则认为已达到目标AUC。受试者的入组将持续进行，开始接受给定起始剂量的受试者将继续接受该剂量，直至根据其个体药代动力学评价需要调整个体受试者剂量。基线和研究疗效评价将包括血浆HIV RNA水平、CD 4计数以及病毒基因型和表型耐药分析。基线和研究安全性评价将包括监测不良事件、临床实验室检查、体格检查和生命体征。在48周结束时，受试者将可以选择通过DuPont Merck方案继续接受266研究。入组结束，新版本的方案将随访时间延长了52周。

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. This is a 48-week, open-label, AUC-controlled, multicenter study. Sixty children will be enrolled. All subjects will receive DMP 266 and nelfinavir. Concomitant use of nucleoside reverse transcriptase inhibitors (NRTI) will be permitted, but they will not be supplied through this protocol. The initial target AUC for DMP 266 will be between 190 and 380. The initial starting dose for children will be 600 mg adjusted for body size. The starting dose for subjects will be adjusted on the basis of the tolerability and DMP 266 plasma concentrations of the first six subjects receiving that dose for two weeks. The target AUC is considered to have been achieved if the dose was tolerated and at least 4 of 6 subjects reached the target AUC. Enrollment of subjects will be ongoing and those begun on a given starting dose will continue on that dose until individual subject dose adjustments are needed according to their individual pharmacokinetics evaluations. Baseline and study efficacy evaluations will include plasma HIV RNA levels, CD4 counts, and viral genotypic and phenotypic resistance analyses. Baseline and study safety evaluations will include the monitoring of adverse experiences, clinical laboratory tests, physical examinations and vital signs. At the end of 48 weeks, subjects will be given the option to continue DMP 266 off-study through a DuPont Merck protocol. Closed to enrollment, new version of protocol extends follow up an additional 52 weeks.