Improving Antiretroviral Management for HIV

该项目的目标是对艾滋病毒感染者进行高质量的患者导向研究， 侧重于回答有关抗逆转录病毒治疗的临床和发病机制问题， 评估新的和新兴的战略，以改善抗逆转录病毒治疗的临床管理。的 该项目的中心假设是，精心计划和分析的研究不仅可以回答 关于特定治疗组合的问题，但也可以提供对发病机制的见解， 治疗反应，并确定战略，以管理病人在诊所。指导年轻的调查人员 （M.P.H.学生，传染病研究员和初级教师）将是这个项目的中心目标。这些 目标将通过构思、设计、启动、执行和分析随机 与当地（UCSD AVRC）、全州（加州协作治疗）合作开展对照试验 组[CCTG]）和国家（艾滋病临床试验组[ACTG]）临床试验组织。为总 作为CCTG的首席研究员，我将能够继续促进发展的传统， 通过积极参与CCTG研究的初级研究者。主要研究主题是 了解抗逆转录病毒治疗反应关系及其对发病机制的影响， 艾滋病毒的管理。具体目标是： 1)通过评估TDF + ABC治疗失败的机制， 核苷血浆和细胞内的免疫应答关系。该研究将使用一种独特的临床 评价相互作用的试验设计（交叉、短期病毒动力学的药代动力学评价） TDF和ABC之间。 2)明确抗逆转录病毒治疗中的免疫应答关系。目标2A： 评价治疗药物监测（TDM）对改善治疗和预后的价值。 抗逆转录病毒疗法目的2B：定义遗传差异的影响（由等位基因变体定义）。 单核苷酸多态性）对抗逆转录病毒药物洛匹那韦（lopinavir）的暴露和反应的影响。

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.