The Impact of HLA in Children Receiving HAART

HLA 对接受 HAART 的儿童的影响

• 批准号: 6915225
• 负责人: AKIHIKO SAITOH
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915225
• 关键词: AIDS therapy; MHC class I antigen; MHC class II antigen; adolescence (12-20); antiviral agents; biomarker; children; clinical research; combination chemotherapy; cytokine; cytotoxic T lymphocyte; drug resistance; enzyme linked immunosorbent assay; gene mutation; genetic polymorphism; genetic susceptibility; helper T lymphocyte; human subject; patient oriented research; therapy compliance

DESCRIPTION (provided by applicant): This application for a Mentored Patient-Oriented Research Career Developmental Award (K23) seeks support for Akihiko Saitoh, M.D., who is currently a Clinical Instructor in Pediatric Infectious Diseases at University of California, San Diego. Under the mentorship of Stephen A. Spector, M.D., Dr. Saitoh will continue to pursue his investigation into the human leukocyte antigen (HLA) that impact on the response to highly active antiretroviral therapy (HAART) in human immunodeficiency virus type-1 (HIV-1) infected children. An additional period of support for clinical research under Dr. Spector's mentorship will allow Dr. Saitoh to expand his repertoire of skills in the field of immunology related to HIV-1. Development of these skills will be essential to help ensure that Dr. Saitoh will succeed in achieving his long-term career goal of becoming an independent physician scientist in an academic medical institution. In this application, Dr. Saitoh proposes to investigate the relationship between HLA class I and class II polymorphisms and the response to HAART in HIV-1 infected children. The specific aims of this proposal are: Aim I: To determine the influence of HLA class I alleles in response to HAART in HIV-1 infected children. Aim II: To evaluate escape mutants through cytotoxic T lymphocyte (CTL) in the specific HLA restricted sites in HIV-1 infected children with virologic failure. Aim III: To determine the influence of HLA class II alleles in response to HAART in HIV-1 infected children. The information learned from this research will help to predict rates of the response to HAART depending upon a child's HLA polymorphisms and has the potential to enable antiretroviral therapy to be optimized for the treatment of a given child with the least toxicity. This research will also suggest modes of pathogenesis that can lead to the development of vaccine strategies.

描述（由申请人提供）：本申请以患者为导向的研究职业发展奖（K23）寻求对医学博士斋藤明彦（Akihiko Saitoh）的支持，他目前是加州大学圣地亚哥分校儿科传染病的临床讲师。在医学博士 Stephen A. Spector 的指导下，Saitoh 博士将继续研究人类白细胞抗原 (HLA) 对人类免疫缺陷病毒 1 型 (HIV) 高效抗逆转录病毒治疗 (HAART) 反应的影响-1) 受感染的儿童。在 Spector 博士的指导下对临床研究的额外支持将使 Saitoh 博士能够扩展他在 HIV-1 相关免疫学领域的技能。这些技能的发展对于确保 Saitoh 博士成功实现成为学术医疗机构的独立医师科学家这一长期职业目标至关重要。 在本申请中，Saitoh 博士提议研究 HLA I 类和 II 类多态性与 HIV-1 感染儿童对 HAART 的反应之间的关系。该提案的具体目标是： 目标 I：确定 HLA I 类等位基因对 HIV-1 感染儿童的 HAART 反应的影响。目标 II：通过病毒学失败的 HIV-1 感染儿童特定 HLA 限制位点的细胞毒性 T 淋巴细胞 (CTL) 评估逃逸突变体。目标 III：确定 HLA II 类等位基因对 HIV-1 感染儿童对 HAART 反应的影响。从这项研究中获得的信息将有助于根据儿童的 HLA 多态性预测 HAART 的反应率，并有可能使抗逆转录病毒疗法能够以最小的毒性优化特定儿童的治疗。这项研究还将提出可导致疫苗策略开发的发病机制模式。