Improving Antiretroviral Management for HIV

该项目的目标是对感染艾滋病毒的患者进行高质量的以患者为导向的研究 重点回答关于抗逆转录病毒治疗和基于临床和发病机制的问题 评估改善抗逆转录病毒治疗临床管理的新战略和新兴战略。这个 该项目的中心假设是，仔细规划和分析的研究不仅可以回答 关于具体治疗组合的问题，但也可以提供对 治疗反应和确定在诊所管理病人的策略。指导年轻的调查人员 (M.P.H.学生、传染病研究员和初级教员)将是该项目的中心目标。这些 目标将通过构思、设计、发起、实施和分析随机化来实现 与当地(UCSD AVRC)、全州(加州合作治疗)合作的对照试验 组[CCTG])和国家(艾滋病临床试验组[ACTG])临床试验组织。作为一个整体 CCTG首席调查员，我将能够延续促进 初级调查人员通过积极参与CCTG研究。主要的研究主题是 了解抗逆转录病毒暴露-反应关系及其对发病机制和 艾滋病毒的管理。具体目标是： 1)通过评价TDF+ABC治疗失败的机制，探讨TDF+ABC治疗失败的机制 核苷血浆和细胞内暴露-反应关系。这项研究将使用一种独特的临床 试验设计(交叉试验、短期病毒动力学药代动力学评价)以评估相互作用 在TDF和ABC之间。 2)明确抗逆转录病毒暴露-反应关系在艾滋病毒治疗中的作用。目标2 A：达到 评价治疗药物监测(TDM)对改善心力衰竭的管理和预后的价值 抗逆转录病毒治疗。目标2B：定义遗传差异(由等位基因变异定义)的影响 单核苷酸多态)与抗逆转录病毒药物洛匹那韦的暴露和反应有关。

The goal of this project is to conduct high quality patient oriented research with HIV infected patients which focuses on answering clinical and pathogenesis based questions concerning antiretroviral therapy and evaluates new and emerging strategies to improve the clinical management of antiretroviral therapy. The central hypothesis of the project is that carefully planned and analyzed studies can not only answer questions about specific treatment combinations, but can also provide insight into the pathogenesis of treatment responses and define strategies to manage patients in the clinic. Mentoring young investigators (M.P.H. students, Infectious Disease fellows, and junior faculty) will be a central goal of this project. These goals will be accomplished by conceiving, designing, initiating, carrying out, and analyzing randomized controlled trials in collaboration with local (UCSD AVRC), statewide (California Collaborative Treatment Group [CCTG]), and national (AIDS Clinical Trials Group [ACTG]) clinical trials organizations. As the overall Principal Investigator of the CCTG, I will be able to continue the tradition of fostering the development of junior investigators through active participation in CCTG studies. The primary research theme is to understand the antiretroviral exposure-response relationship and its implications for the pathogenesis and management of HIV. The specific aims are: 1) To examine the mechanistic pathways leading to therapeutic failure of TDF + ABC by evaluating nucleoside plasma and intracellular exposure-response relationships. The study will use a unique clinical trial design (cross-over, pharmacokinetic evaluation of short-term viral dynamics) to evaluate the interaction between TDF and ABC. 2) To define the role of antiretroviral exposure-response relationships in HIV therapeutics. Aim 2A: To evaluate the value of therapeutic drug monitoring (TDM) to improve the management and outcome of antiretroviral therapy. Aim 2B: To define the impact of genetic differences (defined by allelic variants of single nucleoside polymorphisms) on exposure and response to lopinavir, the antiretroviral agent.