Virologic and host factors contributing to HIV control in elite controllers

描述（由申请人提供）：这是一份K23奖的申请，申请对象是加州大学旧金山分校成人传染病研究员畑野博裕博士，她是一名以患者为导向的hiv感染精英控制者转化研究的年轻研究者。精英控制者是在没有抗逆转录病毒治疗的情况下保持“检测不到”血浆HIV-1 RNA水平的hiv抗体个体。K23奖将为Hatano博士提供必要的支持，以实现以下目标：(1)在精英控制者中恢复，量化和表征HIV；(2)研究宿主与病毒学因子之间的相互作用，这些因素有助于在精英控制者中进行有效的病毒学控制；(4)发展独立的、基于临床的转化研究事业。为了实现这些目标，Hatano博士组建了一个指导团队，由她的主要导师Steven G. Deeks博士和三位共同导师组成：临床病毒学家和HIV潜伏期专家Joseph K. Wong博士；具有HIV感染免疫学专长的免疫学家Joseph (Mike) McCune博士；以及传染病和流行病学专家杰弗里·n·马丁博士。尽管高活性抗逆转录病毒疗法（HAART）在降低与艾滋病毒感染相关的发病率和死亡率方面取得了良好的效果，但长期疗效、毒性、成本和终身坚持治疗方面的挑战仍然存在。因此，需要检查根除模型，以阐明可能使根除成为可能的潜在宿主和病毒因素。精英控制者群体就是这样一个模型。尽管罕见，精英控制者提供了一个独特的机会来研究自然发生的持续控制艾滋病毒的模式。Hatano博士将确定有助于在精英控制者中有效控制艾滋病毒的病毒学因素（目标1）和宿主因素（及其相互作用）（目标2），她将检查他们中是否有一部分“清除”了他们的艾滋病毒感染（目标3）。这项研究将为Hatano博士提供技能和初步数据，以成功竞争R34（4年级）和U01（5年级）NIH拨款支持，这将特别关注精英控制者中的艾滋病毒潜伏期和艾滋病毒控制，以及HAART治疗或其他旨在消耗艾滋病毒的方法是否可以根除精英控制者中的艾滋病毒。公共卫生相关性：了解精英控制者如何保持其独特的艾滋病毒潜伏期和持久的病毒控制可能影响艾滋病毒治疗策略，加强治疗性疫苗设计工作，并有助于可能根除艾滋病毒。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Hiroyu Hatano, a fellow in adult infectious diseases at the University of California, San Francisco who is establishing herself as a young investigator in patient-oriented translational research of HIV-infected elite controllers. Elite controllers are HIV-antibody individuals who have maintained "undetectable" plasma HIV-1 RNA levels in the absence of antiretroviral therapy. This K23 award will provide Dr. Hatano with the support necessary to accomplish the following goals: (1) to recover, quantify, and characterize HIV in elite controllers; (2) to examine the interactions between host and virologic factors that contribute to effective virologic control in elite controllers; and (4) to develop an independent, clinic-based translational research career. To achieve these goals, Dr. Hatano has assembled a mentoring team comprised of her primary mentor, Dr. Steven G. Deeks, an expert in translational HIV research with a focus on HIV pathogenesis, and three co-mentors: Dr. Joseph K. Wong, a clinical virologist and expert in HIV latency; Dr. Joseph (Mike) McCune, an immunologist with expertise in the immunology of HIV infection; and Dr. Jeffrey N. Martin, an expert in infectious diseases and epidemiology. Although highly active antiretroviral therapy (HAART) has been effective in decreasing the morbidity and mortality associated with HIV infection for patients with access to medical care, the challenges of long-term efficacy, toxicity, cost, and life-long adherence remain. Thus, models of eradication need to be examined in order to elucidate potential host and viral factors that may make eradication possible. One such model is the elite controller cohort. Although rare, elite controllers provide a unique opportunity to study a naturally occurring model of sustained control of HIV. Dr. Hatano will identify both virologic factors (Aim 1) and host factors (and their interactions) (Aim 2) that contribute to the effective control of HIV in elite controllers, and she will examine whether a proportion of them have "cleared" their HIV infection (Aim 3). This research will provide Dr. Hatano with the skills and preliminary data to successfully compete for R34 (Year 4) and U01 (Year 5) NIH grant support that will focus specifically on HIV latency and control of HIV in elite controllers and whether treatment with HAART or others methods aimed at depletion of HIV can eradicate HIV in elite controllers. Public health relevance: Insight into how elite controllers maintain their distinctive version of HIV latency and durable viral control may affect HIV treatment strategies, bolster therapeutic vaccine design efforts, and contribute to the possible eradication of HIV.