Vitamin D status and HIV-related complications in children and young adults

儿童和年轻人的维生素 D 状况和 HIV 相关并发症

• 批准号: 8774918
• 负责人: Allison Ross Eckard
• 金额: $ 4.47万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-02 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8774918
• 关键词: 25-hydroxycholecalciferol-24-hydroxylase; 25-hydroxyvitamin D; Address; Adolescent; Adult; Adverse effects; Affect; African American; Age; Anti-Retroviral Agents; Biological Markers; Blood; C-reactive protein; CAP18 lipopolysaccharide-binding protein; CD4 Lymphocyte Count; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion; Cell Adhesion Molecules; Child; Childhood; Cholecalciferol; Chronic; Clinical Nutrition; Clinical Research; Communicable Diseases; Comorbidity; Data; Development; Disease; Disease Progression; Dose; Double-Blind Method; Enzymes; Etiology; Future; General Population; HIV; HIV Infections; Health; Health Status; High Prevalence; Immune; Immune System Diseases; Individual; Inflammation; Inflammatory; Institute of Medicine (U.S.); Interleukin-6; Learning; Life; Malignant Neoplasms; Mentors; Metabolic; Metabolism; Methods; Myocardial; Oral; Osteoporosis; Overweight; Participant; Patients; Pharmaceutical Preparations; Physicians; Physiologic pulse; Physiological; Plasma; Play; Population; Population Group; Primary Prevention; Process; Public Health; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recruitment Activity; Regimen; Reporting; Research; Research Methodology; Research Personnel; Risk; Risk Assessment; Role; Scientist; Serum; Specialist; Supplementation; Surrogate Markers; TNFR-Fc fusion protein; Testing; Time; Training; Vascular Cell Adhesion Molecule-1; Vascular Smooth Muscle; Vitamin D; Vitamin D Deficiency; Vitamins; antimicrobial; antiretroviral therapy; arm; arterial stiffness; cardiovascular disorder risk; cardiovascular health; cost effective; cytokine; disorder prevention; efficacy testing; endothelial dysfunction; experience; high risk; immune function; improved; intercellular cell adhesion molecule; intimal medial thickening; multidisciplinary; patient population; response; restoration; young adult

DESCRIPTION (provided by applicant): Vitamin D is critical in many physiologic and pathophysiologic processes including inflammatory status, immune function, and cardiovascular health. Vitamin D deficiency is widespread among HIV-infected adults and children. This is particularly alarming since there is a higher risk than the general population for complications like osteoporosis, non-AIDS-defining malignancies, and cardiovascular disease (CVD) - all diseases associated with vitamin D deficiency. It is not known how much vitamin D deficiency heightens the risk of complications like CVD, affects immune function and disease progression, or interferes with optimal treatment in the HIV population. The impact of vitamin D deficiency in the HIV population may be compounded even further since the etiology of HIV-related complications like CVD is thought to be related in part to inflammation and detrimental endothelial effects associated with chronic HIV infection-similar proposed mechanisms as vitamin D deficiency. Data suggest that optimal vitamin D status may be protective against these HIV-related complications, and optimizing vitamin D status with oral supplementation in HIV-infected individuals may improve the risk of HIV-related complications by decreasing inflammation and/or improving endothelial dysfunction, and may improve immune function even in individuals on antiretroviral therapy. Developing suitable repletion strategies is crucial to maximizing health status, particularly in HIV-infected children and young adults, where an opportunity exists for disease prevention. However, the best method of vitamin D repletion is not known, and data suggest that some antiretroviral medications interfere with vitamin D metabolism. Thus, we hypothesize that (1) optimizing vitamin D status to the current Institute of Medicine's (IOM) suggested 25-hydroxyvitamin D (25(OH)D) concentration of e20 ng/mL improves CVD risk, inflammation, and CD4 cell counts in HIV-infected individuals, (2) increasing 25(OH)D concentrations to >30 ng/mL improves CVD risk and inflammation to a greater degree than increasing eto 20 ng/mL (the concentration some experts consider optimal for cardiovascular health), and (3) a "high dose" of oral vitamin D is necessary to achieve 25(OH)D concentrations >30 ng/mL. These hypotheses will be addressed by determining the longitudinal relationships between serum 25(OH)D concentrations, carotid intima-media thickness, pulse wave velocity, pro-inflammatory biomarkers, and CD4 cell counts in HIV-infected children and young adults in a double-blinded, randomized-controlled trial of three different vitamin D dosing regimens given over 24 months in HIV-infected children and young adults (ages 10-25 years) with vitamin D deficiency (25(OH)D <20 ng/mL). We will also evaluate the 25(OH)D concentrations from each arm after 6, 12, and 24 months of supplementation, in order to determine a dose-response relationship. These findings could have a sizable impact on health in this population, since vitamin D therapy is inexpensive and associated with few adverse side effects. The PI is an exceptional candidate who is a pediatric infectious diseases specialist with a proven research focus in the metabolic and cardiovascular complications of HIV. She is mentored by a committed, multidisciplinary team of senior investigators with extensive experience in both mentoring and in the research methodologies relevant to this proposal. Future training in all aspects of clinical research, cardiovascular disease risk assessment, and clinical nutrition is planned to facilitate the PI's development into a successful independent physician scientist.

描述（由申请人提供）：维生素D在许多生理和病理生理过程中至关重要，包括炎症状态，免疫功能和心血管健康。维生素D缺乏症在HIV感染的成年人和儿童中普遍存在。这尤其令人震惊，因为与普通人群相比，骨质疏松症，非辅助性恶性肿瘤和心血管疾病（CVD）（CVD）的风险更高 - 所有与维生素D缺乏症相关的疾病。尚不知道维生素D缺乏症会增加CVD等并发症的风险，影响免疫功能和疾病进展，或者在HIV人群中干扰最佳治疗。维生素D缺乏症对HIV种群的影响可能会进一步复杂化，因为认为与CVD这样的HIV相关并发症的病因被认为部分与炎症和有害的内皮效应有关，与慢性HIV感染相关的相似性机制相关的机制是维生素D缺乏症。数据表明，最佳的维生素D状态可能可以抵抗这些与HIV相关的并发症，并且在HIV感染的个体中优化维生素D状态可能会改善与HIV相关并发症的风险，通过减少炎症和/或改善内皮功能障碍，并可以改善内皮功能，并在抗抗病毒治疗方面的免疫功能提高免疫功能。制定合适的补充策略对于最大化健康状况至关重要，尤其是在艾滋病毒感染的儿童和年轻人中，那里存在预防疾病的机会。但是，尚不清楚维生素D的最佳方法，数据表明某些抗逆转录病毒药物会干扰维生素D代谢。因此，我们假设（1）对当前医学研究所（IOM）优化维生素D状态表明25-羟基维生素D（25（OH）d）E20 ng/ml的浓度可改善CVD风险，炎症，炎症，炎症，CD4细胞计数和CD4细胞计数，并在HIV感染中增加了25（2）的浓度，（2）提高了23（OH）DG（OH）DG（oh）dg/ng/ng/ng/ng/ng/gl> 30 ng/ng/gl> 30 ng/ng/gl> 30 ng/比增加20 ng/mL的程度更高（一些专家认为对心血管健康的最佳浓度）和（3）A口服维生素D的“高剂量”对于达到25（OH）D浓度> 30 ng/ml是必需的。这些假设将通过确定血清25（OH）D浓度，颈动脉内膜厚度，脉搏波速度，促脉冲波速度，促脉冲生物标志物和CD4细胞计数之间的纵向关系，在HIV感染的儿童和年轻人中，在双蓝色的年轻人中，对三个不同的儿童进行了三个不同的儿童，并在三种不同的儿童中受到了24个月的摄影。 （10-25岁）维生素D缺乏症（25（OH）D <20 ng/ml）。为了确定剂量反应关系，我们还将在6、12和24个月后评估每个ARM的25（OH）D浓度。这些发现可能会对该人群的健康产生重大影响，因为维生素D疗法价格便宜，并且几乎没有不良副作用。 PI是一位杰出的候选人，他是一名儿科感染疾病专家，在艾滋病毒的代谢和心血管并发症中进行了良好的研究重点。她由一支坚定的，多学科的高级调查员团队指导，在指导和研究方法方面具有丰富的经验与该建议相关的研究方法。计划在临床研究，心血管疾病风险评估和临床营养的各个方面进行未来的培训，以促进PI的发展成为成功的独立医师科学家。