Southern California Primary Infection Program

描述（由申请人提供）：南加州原发性感染项目包括圣地亚哥和洛杉矶的站点，具有识别急性和早期HIV感染的大量队列的跟踪记录。这些队列参与了自然史、发病机制和抗逆转录病毒药物和疫苗治疗干预的纵向研究。一系列优秀的合作已经完成了表征HIV动力学，细胞凋亡，CTL和CD4增殖反应，中和抗体和HIV耐药传播的研究。这些研究包括在圣地亚哥协调的现场和aiedrp范围内的研究。正在进行的和拟议的研究包括CD4和CD8对全长HIV阅读框的反应的特征，免疫反应对HIV共识和自身序列的相对贡献，对自体病毒产生中和抗体（nAb）反应，HIV全长序列对每种免疫反应的逃逸突变的出现，Nef在CTL控制HIV感染和逃逸中的作用。生殖器分泌物中HIV的群体生物学，以及原发性感染中潜伏HIV感染的动态。我们还协调了另一项aiedrp范围内CTL反应的研究，为治疗性疫苗研究做准备。这些研究不仅有助于更好地描述原发性艾滋病毒感染的自然历史和发病机制，还将为设计预防艾滋病毒传播的策略、减少继发性艾滋病毒耐药性以及设计和评估预防性和治疗性疫苗的策略提供宝贵的信息。这一应用的一个主要组成部分是承诺提供最先进的数据管理系统和方法，能够支持多个地方调查人员的项目，并补充AIEDRP中央数据库的资源。我们将开发一套网上资源和通讯技术，以促进学术交流、远程协作、信息发布、教育和培训。

DESCRIPTION (provided by applicant): The Southern California Primary Infection Program includes sites in San Diego and Los Angeles with a track record of identifying substantial cohorts with acute and early HIV infection. These cohorts have participated in longitudinal studies of natural history, pathogenesis, and therapeutic interventions with both antiretroviral drugs and vaccines. A series of excellent collaborations have resulted in completed studies characterizing HIV dynamics, apoptosis, CTL and CD4 proliferate responses, neutralizing antibody, and transmission of HIV drug resistance. These studies consist of both site and AIEDRP-wide studies coordinated in San Diego. Ongoing and proposed studies include the characterization of CD4 and CD8 responses to full length HIV reading frames, the relative contributions of immune responses to consensus and autologous sequences of HIV, the generation of neutralizing antibody (nAb) responses to autologous virus, the emergence of escape mutations over the full length sequence of HIV to each of these immune responses, the role of Nef in CTL control of HIV infection and escape from it, the population biology of HIV in genital secretions, and the dynamics of latent HIV infection in primary infection. We have also coordinated an additional AIEDRP-wide study of CTL responses in preparation for a therapeutic vaccine study. These studies will not only help to better characterize the natural history and pathogenesis of primary HIV infection, they will provide invaluable information to design strategies to prevent HIV transmission, to reduce secondary HIV drug resistance and to design and evaluate strategies for both prophylactic and therapeutic vaccines. A major component of this application is also the commitment to provide a state-of-the-art data management system and methods capable of supporting the projects of multiple local investigators as well as complimenting the resources of the central AIEDRP database. We will develop a set of on-line resources and communications technologies that facilitate scholarly exchange, distance-independent collaboration, information dissemination, education and training.