Immunological control of HIV in vivo

在急性HIV感染期间由病毒复制引起的免疫应答和病理事件决定了患者中HIV的后期水平，以及偶尔能够在没有药物治疗的情况下控制HIV的个体的出现。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HIV的观察结果也表明，在急性感染期间，关键的致病事件是有效的。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，并提供了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HIV控制相关。该项目将有助于整个计划的业务和科学目标。纳入一项临床方案，为符合条件的感染者提供抗逆转录病毒治疗，这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的测定法测量）与在没有ART的情况下控制HIV复制的相关性，为该项目的主要免疫学问题做出贡献。 受试者在急性感染的最初几天决定开始治疗之前。然而，由于将纳入急性和早期HIV感染，受试者将在感染发作后的不同时间开始治疗。在这些受试者开始ART之前进行的连续免疫学测量将提供关于未经治疗的感染中HIV特异性免疫应答演变的横截面数据。

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.