Virologic and host factors contributing to HIV control in elite controllers

描述(由申请人提供)：这是一份K23奖项的申请书，授予Hiroyu Hatano博士，她是加州大学旧金山分校的成人传染病研究员，在面向患者的艾滋病毒感染精英控制者的翻译研究中确立了自己的年轻研究员地位。精英控制者是指在没有抗逆转录病毒治疗的情况下，保持“无法检测到”的血浆HIV-1RNA水平的艾滋病毒抗体携带者。这一K23奖项将为Hatano博士提供必要的支持，以实现以下目标：(1)恢复、量化和描述精英控制器中的艾滋病毒；(2)检查宿主和病毒学因素之间的相互作用，这些因素有助于精英控制器中有效的病毒学控制；以及(4)发展独立的、以临床为基础的翻译研究事业。为了实现这些目标，Hatano博士组建了一个指导团队，成员包括她的主要导师Steven G.Deek博士和三位共同导师：临床病毒学家和HIV潜伏期专家Joseph K.Wong博士；擅长HIV感染免疫学的免疫学家Joseph(Mike)McCune博士；以及传染病和流行病学专家Jeffrey N.Martin博士。虽然高效抗逆转录病毒疗法(HAART)已经有效地降低了与艾滋病毒感染相关的发病率和死亡率，但长期疗效、毒性、成本和终生依从性的挑战仍然存在。因此，需要研究根除模式，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种模式。虽然很少见，但精英控制者提供了一个独特的机会来研究持续控制艾滋病毒的自然发生模式。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)，她将检查其中一部分人是否已“清除”其艾滋病毒感染(目标3)。这项研究将为Hatano博士提供成功竞争R34(第4年)和U01(第5年)NIH赠款支持的技能和初步数据，这些资助将特别侧重于精英控制者中的HIV潜伏期和HIV的控制，以及HAART或其他旨在耗尽HIV的治疗方法是否可以根除精英控制者中的HIV。公共卫生相关性：洞察精英管制员如何保持其独特的艾滋病毒潜伏期和持久的病毒控制，可能会影响艾滋病毒治疗战略，支持治疗性疫苗设计努力，并为可能的根除艾滋病毒做出贡献。

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.