DEVELOPMENTAL IMMUNOLOGY

在过去的几年里，越来越明显的是，进一步 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-宿主相互作用的理解。一直以来 假设病毒特异性效应机制在 限制艾滋病毒在体内的复制，因此是一个重要的 临床和免疫学进展率的决定因素 艾滋病毒感染。这一概念是大前提 以免疫为基础的艾滋病毒感染疗法的原理。此外, 一项最近完成的对最初的安慰剂对照的统计分析 对齐多夫定的研究增加了部分重建的可能性 HIV特异性免疫反应可能导致二次抗病毒 可能进一步有助于抗逆转录病毒疗效的作用 探员们。随着临床试验变得越来越复杂，它将是 至关重要的是，它们的设计和实施要充分理解 HIV发病机制的概念。这样一种方法执行了临床 试验将导致更有效地使用日益有限的 可用于临床研究的资源，并将提供 为测试与艾滋病毒发病机制有关的假说提供了额外的场地。 我们小组对细胞介导的免疫反应特别感兴趣 爱滋病毒。在这个项目中，我们建议将我们的兴趣和专业知识应用于 这一领域是基于免疫的治疗的临床试验，以及 抗逆转录病毒化疗。我们期望这些研究将 为治疗方法的可行性提供重要的见解 它们寻求增强病毒特异性免疫反应，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.研究抗逆转录病毒疗法和基于免疫的疗法对 HIV特异性细胞免疫(CMI)。 2.确定以下项目赋予的生存利益的程度 不能用CD4+细胞变化解释的抗逆转录病毒药物 仅计数一项就可能归因于艾滋病毒特异性CMI的变化。 3.作为表演和表演的参考实验室 HIV特异性细胞免疫反应检测方法的标准化 在其他ACTG站点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.