PACTG P1021: EMTRICITABINE IN COMBINATION WITH EFAVIRENZ & DIDANOSINE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。PACTG P1021是一项I/II期开放标签研究，将评估每天一次的三联疗法(FTC、EFV和DDI)在接受抗逆转录病毒治疗(围产期预防56天，累积抗逆转录病毒治疗7天)并具有筛查血浆HIV-1RNA水平和5000拷贝/毫升的HIV-1感染儿童患者(90天至21岁)中的长期安全性和抗病毒活性。这项研究将招募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。受试者将根据他们进入时的年龄进行分层；每个年龄组至少有6名受试者(90天至3岁；3至12岁；13至21岁)，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DDI-EC口服溶液的肠溶制剂和DDI儿科粉剂的生物利用度。治疗第2周的密集PK研究将用于确定是否需要调整一种、两种或所有三种研究药物的初始剂量。剂量调整将在受试者的下一次研究访问中实施。P1021将评估病毒学和免疫学反应与PK水平、粘附措施、细胞色素P4503A药物代谢酶的基因类型、最近的胸腺移民和HIV RNA决定因素之间的关系。将对治疗过程中免疫功能的变化进行详细研究。每个受试者的艾滋病毒耐药性突变谱将与病毒学、药理学和免疫学反应标记物相关联，以评估耐药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.