OPTIMIZING ANTIRETROVIRAL THERAPY IN HIV-INFECTED CHILDREN AND ADOLESCENTS

优化感染艾滋病毒的儿童和青少年的抗逆转录病毒治疗

• 批准号: 7608360
• 负责人: NATELLA Y RAKHMANINA
• 金额: $ 15.52万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 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/7608360
• 关键词: ABCB1 gene; Address; Adolescent; CD4 Lymphocyte Count; CYP2C19 gene; CYP3A4 gene; CYP3A5 gene; Child; Childhood; Classification; Clinical; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Kinetics; Funding; Genes; Genetic; Genetic Variation; Goals; Grant; HIV Infections; Institution; Investigation; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Pharmacogenetics; Prevalence; Protease Inhibitor; Protocols documentation; Reaction; Research; Research Personnel; Resources; Source; Toxic effect; United States National Institutes of Health; Viral Load result; antiretroviral therapy; base; cohort; improved; viral RNA; virtual

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. The long-term goal of the research investigation is to improve dosing of protease inhibitors (PIs) in HIV-infected children, leading to improved outcome and decreased adverse drug reactions. In order to do so, the protocol addresses the following specific aims: Specific Aim 1: Determine the prevalence of genetic variations in CYP2C19, CYP3A4, CYP3A5, and MDR-1 genes in a cohort of children and adolescents with HIV infection. Specific Aim 2: Evaluate the relationship of this genetic variability to the pharmacokinetic parameters (Cmin, Cmax, AUC) and toxicity (graded by the DAIDS classification) of protease inhibitors in pediatric patients with HIV infection. Specific Aim 3: Evaluate the impact of dose adjustment of protease inhibitors based on pharmacogenetic profile and virtual inhibitory quotient (VIQ) on clinical outcome (measured by HIV-RNA viral load and CD4+ cell count changes) and toxicity (graded by the DAIDS classification) in pediatric patients with HIV infection.

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。子项目和 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。 该研究的长期目标是改善 HIV 感染儿童的蛋白酶抑制剂 (PI) 剂量，从而改善结果并减少药物不良反应。 为此，该协议解决了以下具体目标： 具体目标 1：确定感染 HIV 的儿童和青少年队列中 CYP2C19、CYP3A4、CYP3A5 和 MDR-1 基因遗传变异的患病率。 具体目标 2：评估这种遗传变异与 HIV 感染儿科患者中蛋白酶抑制剂的药代动力学参数（Cmin、Cmax、AUC）和毒性（按 DAIDS 分类分级）的关系。 具体目标 3：根据药物遗传学谱和虚拟抑制商 (VIQ) 评估蛋白酶抑制剂剂量调整对临床结果（通过 HIV-RNA 病毒载量和 CD4+ 细胞计数变化衡量）和毒性（根据 DAIDS 分类分级）的影响感染艾滋病毒的儿科患者。