PACTG P1021: EMTRICITABINE IN COMBINATION WITH EFAVIRENZ & DIDANOSINE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。PACTG P1021是一项I/II期开放标签研究，将评估每日一次三联用药方案（FTC、EFV和ddI）在HIV-1感染的儿科受试者（90天至21岁）中的长期安全性和抗病毒活性，这些患者最初接受抗逆转录病毒治疗（<56天围产期预防，<7天累积抗逆转录病毒治疗），并筛查血浆HIV-1 RNA水平为50 000拷贝/mL。该研究将招募36至42名可评估的HIV-1感染儿童受试者，他们将接受至少48周的治疗。受试者将根据入组时的年龄进行分层；每个年龄组（90天至<3岁；3至12岁；13至21岁）至少入组6名受试者，以便在每个年龄组收集足够的药代动力学数据。PACTG P1021将表征FTC的处置，将确定ddI- ec QD的PK数据，并比较肠溶包膜制剂与ddI小儿口服液的生物利用度。在治疗第2周进行强化PK研究，以确定是否需要调整一种、两种或全部三种研究药物的初始剂量。剂量调整将在受试者下一次研究访问时实施。P1021将评估病毒学和免疫反应与PK水平、依从性措施、细胞色素P4503A药物代谢酶基因型、近期胸腺迁移和HIV RNA决定因子之间的关系。治疗期间免疫功能变化的详细研究将被执行。每个受试者的HIV抗性突变谱将与病毒学、药理学和免疫反应标志物相关联，以评估抗性在病毒学失败中的作用。

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. PACTG P1021 is a Phase I/II open label study which will evaluate the long-term safety and antiviral activity of a once-daily triple combination regimen (FTC, EFV, and ddI) in HIV-1 infected pediatric subjects (90 days to 21 years of age) who are nanve to antiretroviral therapy (<56 days perinatal prophylaxis, <7 days of cumulative antiretroviral treatment) and have screening plasma HIV-1 RNA levels >5000copies/mL. The study will enroll 36 to 42 evaluable HIV-1 infected pediatric subjects who will receive treatment for a minimum of 48 wks. Subjects will be stratified based on their age at entry; at least 6 subjects will be enrolled per age group (90 days to <3 years of age; 3 to 12 years of age; and 13 to 21 years of age) to allow adequate pharmacokinetic data to be collected in each age group. PACTG P1021 will characterize the disposition of FTC, will determine the PK data for ddI-EC QD, and compare the bioavailability of the enteric coated formulation with the ddI pediatric powder for oral solution. Intensive PK studies at Week 2 of treatment will be used to determine if dose adjustments of the initial doses of one, two, or all three study medications are needed. Dose adjustments will be implemented at the subject's next study visit. P1021 will evaluate the association between virologic and immunologic responses and PK levels, adherence measures, genotypes of cytochrome P4503A drug metabolizing enzymes, recent thymic emigrants, and HIV RNA determinants. Detailed studies of immunologic function changes during therapy will be performed. The HIV resistance mutation profile of each subject will be correlated with virologic, pharmacologic and immunologic response markers in order to evaluate the role of resistance in virologic failure.