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

PACTG P1021：恩曲他滨与依非韦伦联用

• 批准号: 7604244
• 负责人: Ram Yogev
• 金额: $ 1.21万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604244
• 关键词: PACTG; P1021; EMTRICITABINE; COMBINATION; EFAVIRENZ

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 naive, 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 naive, 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 naive 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-naive 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 主要目的： 1) 确定未接受或接触非常有限的抗 HIV 治疗的 HIV 感染儿科受试者每日一次 FTC + EFV + ddI 治疗方案的长期安全性和耐受性。 2) 确定每日一次的 FTC + EFV + ddI 方案在治疗未接触过或接触过抗逆转录病毒药物的儿童受试者中的抗病毒活性。 其次：1) 确定儿科人群中 FTC 的稳态药代动力学 (PK) 参数，并检查 FTC 处置中潜在的年龄相关差异。 2) 每日一次肠溶制剂（ddI-EC）给药后获得 ddI 的 PK 数据，并确定其与口服溶液制剂 ddI 儿科粉剂的生物利用度比较。 3) 确定给予目前推荐的儿科剂量后的 EFV 全身暴露量。 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，该结果由血浆 HIV-RNA 抑制的程度和持续时间决定。 5)确定每个受试者中细胞色素P450 3A (CYP3A)药物代谢酶的基因型分布。 6) 测量 CD4 介导的针对 HIV 和其他微生物抗原的免疫反应，并描述它们与治疗诱导的病毒学反应以及循环 T 细胞数量和表型变化的关系。 7) 测量最近的胸腺迁移并确定它们与循环初始 CD4 细胞数量和治疗病毒学反应的关系。 8) 确定抗逆转录病毒耐药性在每日一次 FTC + EFV + ddI 治疗方案病毒学失败中的作用，并评估超灵敏 HIV-RNA 测定作为初治儿科受试者病毒学失败早期指标的用途。 9) 在探索性分析中检查受试者对研究方案的依从性是否较差，病毒学反应是否较差，或病毒学失败的风险是否增加，或产生抗逆转录病毒耐药性的风险是否增加。