Interactions Between Olive Leaf Extract and HIV Drugs

橄榄叶提取物与艾滋病毒药物之间的相互作用

• 批准号: 6746550
• 负责人: SYLVIA LEE-HUANG
• 金额: $ 35.88万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-26 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746550
• 关键词: AIDS therapy; HIV infections; alternative medicine; antiAIDS agent; combination chemotherapy; drug interactions; human immunodeficiency virus; indinavir; laboratory rat; lamivudine; pharmacokinetics; plant extracts; virus infection mechanism; zidovudine

DESCRIPTION (provided by applicant): Recent studies indicate that over half of patients with HIV/AIDS take complementary and alternative medicines (CAM) along with their prescription anti-HIV drugs. Despite this, little is known about the pharmacology, pharmacokinetics, or pharmacodynamics of CAMs, or how they interact with standard anti-HIV regimens. Adverse interactions may lead to profound clinical consequences, the development of resistance, and failure of antiretroviral therapy. Many patients on highly active anti-retroviral therapy (HAART) regimens use olive leaf extract (OLE) to lessen the side effects of HAART, and for its own anti-HIV effects. There is therefore an urgent need to understand the anti-HIV effects of OLE and how it interacts with HAART medications. We propose three specific aims: First, to use rigorous drug interaction studies to define whether the effects of OLE are additive, synergistic, or antagonistic with 3TC, AZT, and IND, a standard triple-drug HAART regimen. Second, to define the effects of OLE on three specific steps in the viral life cycle: viral binding, reverse transcription, and protease processing of viral proteins. Third, to test the in vivo pharmacokinetics of OLE, and whether OLE affects the intracellular accumulation of anti-HIV drugs by effects on efflux and influx drug transport systems. We propose to use well-characterized OLE preparations standardized by LC-MS. Our long term goals are to understand the molecular mechanisms by which OLE exerts anti-HIV effects, and to promote synergistic effects while avoiding antagonistic interactions during anti-HIV therapy. We hope that this information will provide an important knowledge base for anti-HIV therapy of OLE alone or in combination with HAART, as well as contribute to our understanding of viral pathogenesis.

描述（由申请人提供）：最近的研究表明，超过一半的艾滋病毒/艾滋病患者在服用补充和替代药物（CAM）的同时还服用抗艾滋病毒处方药。尽管如此，人们对 CAM 的药理学、药代动力学或药效学，或者它们如何与标准抗 HIV 治疗方案相互作用的情况知之甚少。不良相互作用可能导致深远的临床后果、耐药性的产生和抗逆转录病毒治疗的失败。许多接受高效抗逆转录病毒疗法 (HAART) 方案的患者使用橄榄叶提取物 (OLE) 来减轻 HAART 的副作用，并发挥其自身的抗 HIV 作用。因此，迫切需要了解 OLE 的抗 HIV 作用以及它如何与 HAART 药物相互作用。我们提出三个具体目标：首先，使用严格的药物相互作用研究来确定 OLE 的作用与 3TC、AZT 和 IND（标准三药 HAART 方案）是否相加、协同或拮抗。其次，定义 OLE 对病毒生命周期中三个特定步骤的影响：病毒结合、逆转录和病毒蛋白的蛋白酶加工。第三，测试OLE的体内药代动力学，以及OLE是否通过影响流出和流入药物转运系统来影响抗HIV药物的细胞内积累。我们建议使用经过 LC-MS 标准化、特征良好的 OLE 制剂。我们的长期目标是了解 OLE 发挥抗 HIV 作用的分子机制，并在抗 HIV 治疗过程中促进协同作用，同时避免拮抗相互作用。我们希望这些信息将为OLE单独或联合HAART的抗HIV治疗提供重要的知识基础，并有助于我们了解病毒发病机制。