Virologic and host factors contributing to HIV control in elite controllers

有助于精英控制者艾滋病毒控制的病毒学和宿主因素

• 批准号: 7623148
• 负责人: HIROYU HATANO
• 金额: $ 12.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623148
• 关键词: Acute; Adherence; Adult; Adverse effects; Affect; Alleles; Anti-Retroviral Agents; Antibodies; Antibody Formation; Applications Grants; Biological Assay; CCR5 gene; California; Caring; Characteristics; Clinic; Clinical; Coculture Techniques; Communicable Diseases; Competence; Cytotoxic T-Lymphocytes; DNA; Data; Defective Viruses; Detection; Equilibrium; Evolution; Failure; Genetic; Genetic Risk; Genotype; Goals; Grant; HIV; HIV Antibodies; HIV Infections; HIV antibody positive; HIV-1; Haplotypes; Highly Active Antiretroviral Therapy; Host Factor 1 Protein; Immunologist; Immunology; Individual; Infection; Infectious Disease Epidemiology; Integration Host Factors; Knowledge; Living Costs; Logistic Regressions; Measures; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Minority; Modeling; Morbidity - disease rate; Mutation; Optics; Pathogenesis; Patients; Pharmaceutical Preparations; Phenotype; Plasma; Prevalence; Publishing; RNA; Recovery; Regression Analysis; Reporting; Research; Research Personnel; Risk; Role; Sample Size; San Francisco; Series; Serological; T-Lymphocyte; Testing; Time; Toxic effect; Translational Research; United States National Institutes of Health; Universities; Vaccine Design; Variant; Viral; Viremia; Virus; Western Blotting; antiretroviral therapy; base; career; clinical phenotype; cohort; comparison group; density; insight; mortality; novel; novel therapeutic intervention; patient oriented; prevent; protective effect; public health relevance; research study; response; skills; therapeutic vaccine; transmission process; treatment strategy

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.

描述（由申请人提供）：这是一份K23奖的申请书，申请人是加州大学旧金山分校弗朗西斯科的成人传染病研究员，她正在成为一名年轻的研究人员，从事以患者为导向的艾滋病毒感染精英控制者的转化研究。精英控制者是HIV抗体个体，他们在没有抗逆转录病毒治疗的情况下保持“不可检测”的血浆HIV-1 RNA水平。该K23奖项将为波多野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）检查有助于精英控制者有效病毒控制的宿主和病毒学因素之间的相互作用;（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，波多野博士组建了一个指导团队，由她的主要导师史蒂文G。Deeks博士，一位专注于HIV发病机制的HIV转化研究专家，和三位共同导师：临床病毒学家和艾滋病毒潜伏期专家黄博士、免疫学家约瑟夫（迈克）麦克库恩博士和杰弗里N。马丁是传染病和流行病学专家。尽管高效抗逆转录病毒疗法（HAART）已有效降低与艾滋病毒感染相关的发病率和死亡率，为患者提供医疗护理，长期疗效，毒性，成本和终身坚持的挑战仍然存在。因此，根除模型需要进行检查，以阐明潜在的宿主和病毒因素，可能使根除。一个这样的模型是精英控制器队列。虽然罕见，精英控制者提供了一个独特的机会，研究自然发生的持续控制艾滋病毒的模型。波多野博士将确定病毒学因素（目标1）和宿主因素（及其相互作用）（目标2），有助于有效控制精英控制者的艾滋病毒，她将检查他们中的一部分人是否已经“清除”他们的艾滋病毒感染（目标3）。这项研究将为波多野博士提供成功竞争R34（4年级）和U 01（5年级）NIH资助的技能和初步数据，这些资助将专门关注精英控制者中的HIV潜伏期和HIV控制，以及HAART治疗或其他旨在消除HIV的方法是否可以根除精英控制者中的HIV。公共卫生相关性：深入了解精英控制者如何保持其独特的HIV潜伏期和持久的病毒控制可能会影响HIV治疗策略，支持治疗性疫苗设计工作，并有助于可能根除HIV。