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: 7376831
• 负责人: Ram Yogev
• 金额: $ 0.32万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376831
• 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 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.

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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。主要：1）确定每天在NANVE或暴露于抗HIV治疗的HIV感染的儿科受试者中，每天服用一次FTC + EFV + DDI的长期安全性和容忍度。 2）确定每天在NANVE治疗或非常有限的抗逆转录病毒暴露的儿科受试者治疗的FTC + EFV + DDI方案的抗病毒活性。次要：1）确定小儿种群中FTC的稳态药代动力学（PK）参数，并检查FTC处置处的潜在年龄相关差异。 2）每天给肠涂层配方（DDI-EC）进行一次DDI的PK数据，并确定其与DDI儿科粉的比较生物利用度用于口服溶液制剂。 3）确定当前建议的小儿剂量后，确定EFV全身暴露。 4）要在探索性分析中检查三种药物（FTC/EFV/DDI）中每种抗逆转录病毒全身暴露与抗逆转录病毒结局的关系，这取决于血浆HIV-RNA抑制的程度和持续时间。 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的分布。 6）测量CD4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细胞数量和表型的变化的关系。 7）测量最近的胸腺移民并确定他们与循环NANVE CD4细胞数量以及对治疗的病毒反应的关系。 8）确定抗逆转录病毒抗性在FTC + EFV + DDI的一次治疗方案中的病毒学衰竭中的作用，并评估使用超敏感HIV-RNA确定的使用作为治疗量的早期病毒学衰竭的使用。 9）在探索性分析中检查依从性研究方案，病毒学反应较差，病毒衰竭的风险增加或增加抗逆转录病毒耐药性的风险是否增加。