DEVELOPMENTAL IMMUNOLOGY

在过去几年中，越来越明显的是， 艾滋病毒药物和疫苗开发的进展将高度依赖于 加深对病毒与宿主相互作用的理解。 已经 假设病毒特异性效应器机制在 限制HIV在体内的复制，因此作为一种重要的 确定临床和免疫学进展率的决定因素 艾滋病毒感染。 这一概念是构成 基于免疫的HIV感染治疗的基本原理。 此外，本发明还提供了一种方法， 最近完成的对初始安慰剂对照组的统计分析 齐多夫定的研究提出了部分重建 HIV特异性免疫应答可能导致继发性抗病毒 可能进一步增强抗逆转录病毒疗效的影响 剂. 随着临床试验变得越来越复杂， 关键是，它们的设计和实施必须充分了解 艾滋病毒发病机制的概念。 这种方法的执行临床 试验将导致更有效地利用日益有限的 可用于临床研究的资源，并将提供 为检验与艾滋病发病机制有关的假设提供了额外的场所。 我们小组对细胞介导的免疫反应特别感兴趣， 艾滋病。 在这个项目中，我们建议运用我们的兴趣和专业知识， 这一领域的临床试验免疫为基础的治疗，和研究 抗逆转录病毒化疗 我们希望这些研究将 为治疗方法的可行性提供重要见解 其寻求增强病毒特异性免疫应答，并可能 抗逆转录病毒药物可能介导有益的间接机制 临床效果 这项建议的具体目标是： 1.研究抗逆转录病毒和免疫疗法对 HIV特异性细胞介导免疫（CMI）。 2.为了确定在多大程度上， 不能通过CD4+细胞的变化来解释的抗逆转录病毒药物 单独计数可能归因于HIV特异性CMI的变化。 3.作为性能的参考实验室， HIV特异性细胞介导的免疫应答测定的标准化 在其他ACTG中心进行的基于免疫的临床试验中。

Over the past several years it has become increasingly clear that further advances in HIV drugs and vaccine development will be highly dependent on deepening the understanding of virus-host interactions. It has been hypothesized that virus specific effector mechanisms play a major role in limiting replication of HIV in vivo, and thus serve as an important determinant in defining the rate of clinical and immunologic progression of HIV infection. This concept serves as the major premise which underlies the rationale for immune based therapies for HIV infection. In addition, a recently completed statistical analysis of the initial placebo controlled study of zidovudine has raised the possibility that partial reconstitution of HIV specific immune responses might result in secondary antiviral effects which might further contribute to the efficacy of antiretroviral agents. As clinical trials become increasingly complex, it will be critical that they be designed and conducted with a full understanding of concepts of HIV pathogenesis. Such an approach the execution of clinical trials will result in a more effective use of increasingly limited resources available for clinical investigation, and will provide an additional venue for the testing of hypotheses related to HIV pathogenesis. Our group has a particular interest in the cell mediated immune response to HIV. In this project we propose to apply our interest and expertise in this area to clinical trials of both immune based therapies, and studies of antiretroviral chemotherapy. It is our expectation that these studies will provide important insights into the feasibility of therapeutic approaches which seek to enhance virus specific immune responses, and into possible indirect mechanisms by which antiretroviral agents might mediate beneficial clinical effects. Specific Aims for this proposal are: 1. To examine the effects of antiretroviral and immune-based therapies on HIV-specific cell-mediated immunity (CMI). 2. To determine extent to which the survival benefit conferred by antiretroviral agents that cannot be explained by changes in CD4+ cell counts alone might be attributable to changes in HIV-specific CMI. 3. To serve as a reference laboratory for the performance and standardization of assays for HIV-specific cell-mediated immune responses in immune-based clinical trials undertaken at other ACTG sites.