PACTG P1021: EMTRICITABINE IN COMBINATION WITH EFAVIRENZ & DIDANOSINE IN ART

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。主要内容：1)确定一种每日一次的FTC+EFV+DDI方案在接受抗HIV治疗的感染HIV的儿童受试者中的长期安全性和耐受性。2)确定每天给药一次的FTC+EFV+DDI方案在治疗NAVE或非常有限的抗逆转录病毒暴露的儿童受试者中的抗病毒活性。第二：1)确定FTC在儿科人群中的稳态药代动力学(PK)参数，并检验与年龄相关的FTC处置的潜在差异。2)获得每日一次口服肠溶制剂(DDI-EC)后DDI的pk数据，并确定其与口服溶液制剂的ddi儿科粉剂的比较生物利用度。3)确定当前推荐的儿科剂量给药后的EFV全身暴露。4)在探索性分析中检查三种药物(FTC/EFV/DDI)中每种药物的抗逆转录病毒全身暴露与抗逆转录病毒结果之间的关系，这取决于血浆HIV-RNA被抑制的程度和持续时间。5)确定细胞色素P4503A(CYP3A)药物代谢酶基因在各受试者中的分布。6)检测CD4介导的对HIV和其他微生物抗原的免疫应答，并描述它们与治疗诱导的病毒学应答以及循环T细胞数量和表型变化的关系。7)测量新近迁出的胸腺细胞，并确定它们与循环中的纳米CD4细胞数量和治疗后的病毒学反应的关系。8)确定抗逆转录病毒耐药性在每日一次的FTC+EFV+DDI治疗方案的病毒学失败中的作用，并评价超灵敏的HIV-RNA检测作为病毒学失败的早期指标在治疗后的儿科受试者中的应用。9)在探索性分析中检查对研究方案依从性较差的受试者是否有更差的病毒学反应，或病毒学失败的风险增加，或产生抗逆转录病毒耐药性的风险增加。

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. Primary: 1) To determine the long-term safety and tolerance of a regime of FTC + EFV + ddI administered once daily in HIV-infected pediatric subjects who are nanve, or have very limited exposure, to anti-HIV therapy. 2) To determine the antiviral activity of a regimen of FTC + EFV + ddI administered once daily in treatment of nanve, or very limited antiretroviral exposed, pediatric subjects. Secondary: 1) To determine the steady state pharmacokinetic (PK) parameters for FTC in a pediatric population and examine potential age related differences in the disposition of FTC. 2) To obtain PK data for ddI following once daily administration of the enteric coated formulation (ddI-EC), and to determine its comparative bioavailability with the ddI pediatric powder for oral solution formulation. 3) To determine the EFV systemic exposure following administration of the currently recommended pediatric doses. 4) To examine in an exploratory analysis, the relationship between antiretroviral systemic exposure for each of the three drugs (FTC/EFV/ddI) and the antiretroviral outcomes as determined by the extent and duration of suppression of plasma HIV-RNA. 5) To determine the distribution of genotypes for cytochrome P450 3A (CYP3A) drug metabolizing enzymes in each subject. 6) To measure CD4 - mediated immune responses to HIV and other microbial antigens and describe their relationship with therapy-induced virologic responses and changes in circulating T cell numbers and phenotype. 7) To measure recent thymic emigrants and determine their relationship with the number of circulating nanve CD4 cells and with virologic response to therapy. 8) To determine the role of antiretroviral resistance in virologic failure of a once-daily treatment regimen of FTC + EFV + ddI, and to evaluate the use of ultrasensitive HIV-RNA determination as an early indicator of virologic failure in treatment-nanve pediatric subjects. 9) To examine in an exploratory analysis whether subjects with poorer adherence to study regimen, have worse virologic responses, or increased risk of virologic failure, or increased risk of developing antiretroviral resistance.