Immunological control of HIV in vivo

在急性HIV感染期间，由病毒复制引起的免疫反应和病理事件决定了患者体内HIV的后期水平，并且偶尔出现能够在没有药物治疗的情况下控制HIV的个体。在急性感染期间开始抗逆转录病毒治疗（ART）可能允许患者随后在没有ART的情况下控制艾滋病毒，这也表明急性感染期间的关键致病事件是有效的。项目1。将评估CD4 T细胞对HIV抗原的反应在体内控制HIV复制中的作用，并提供一个机会来评估在没有抗逆转录病毒治疗（ART）的情况下，哪些类型的CD4反应与控制HIV有关。这个项目将有助于实现整个项目的操作目标和科学目标。纳入向符合条件的感染者提供抗逆转录病毒治疗的临床方案对于招募急性和早期感染受试者至关重要，这些受试者的标本将在本提案的所有项目中进行研究，并提供一种跟踪这些受试者的方法。我们的经验表明，该方案的可用性将成为患者入组这些研究的主要诱因。该项目将通过评估CD4 T细胞对HIV抗原的反应（通过检测CD4反应的几种不同成分来测量）与在没有抗逆转录病毒治疗的情况下控制HIV复制的相关性，为该计划的主要免疫学问题做出贡献。我们强调识别

Immune responses and pathologic events resulting from viral replication during acute HIV infection determine the later level of HIV in a patient, and the emergence of occasional individuals who are able to control HIV without drug therapy. Observations that the initiation of antiretroviral therapy (ART) during acute infection may permit patients to subsequently control HIV without ART also indicate that critical pathogenic events are operative during acute infection. Project 1. will evaluate the role of CD4 T cell responses to HIV antigens in the control of HIV replication in vivo, and provides an opportunity to assess what types of CD4 responses are associated with the control of HIV in the absence of antiretroviral therapy (ART). This project will Contribute to both the operational and the scientific goals of the overall program. The inclusion of a clinical protocol offering antiretroviral therapy to eligible infected individuals is essential for the recruitment of subjects with acute and early infection whose specimens will be studied in all projects of this proposal, and provides a way to follow these subjects. Our experience indicates that the availability of this protocol will serve as a major inducement for the enrollment of patients into these studies. This project will contribute to the major immunological question of the program by assessing the correlation of the development CD4 T cell responses to HIV antigens (as measured by assays examining several different components of the CD4 response) with the control of HIV replication in the absence of ART. We emphasize the identification of subjects during the earliest days of acute infection before they decide to start therapy. However because both acute and early HIV infections will be included, subjects will start therapy at different times after the onset of their infection. Sequential immunological measurements in these subjects before they start ART will provide cross sectional data on the evolution of HIV-specific immune responses in untreated infection.