Vitamin D, drug metabolism, and cardiovascular complications in pediatric HIV

儿科 HIV 患者的维生素 D、药物代谢和心血管并发症

• 批准号: 8511762
• 负责人: GRACE A MCCOMSEY
• 金额: $ 31.71万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511762
• 关键词: 25-hydroxyvitamin D; AIDS prevention; Adult; Affinity; Atherosclerosis; Cardiac; Cardiovascular Diseases; Cardiovascular system; Child; Childhood; Cholecalciferol; Comorbidity; Control Groups; Cross-Sectional Studies; Data; Development; Diabetes Mellitus; Dose; Dyslipidemias; Effectiveness; General Population; HIV; HIV therapy; Heart Diseases; High Prevalence; Hyperglycemia; Hypertension; Immune; Inflammation; Insulin Resistance; Intervention; Life; Link; Lipoproteins; Measures; Mediating; Metabolic; Metabolic syndrome; Metabolism; Morbidity - disease rate; Obesity; Observational Study; Pathway interactions; Patients; Pilot Projects; Population; Prevalence; Randomized; Reporting; Risk; Risk Factors; Serum; Supplementation; Surrogate Markers; Thick; Toxic effect; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; antiretroviral therapy; cardiovascular disorder risk; cardiovascular risk factor; clinical practice; clinically significant; drug metabolism; efavirenz; heart disease risk; improved; inflammatory marker; insulin sensitivity; intima media; non-nucleoside reverse transcriptase inhibitors; pediatric human immunodeficiency virus; urinary; young adult

DESCRIPTION (provided by applicant): Vitamin D functions as a powerful immune modulator and its insufficiency has recently emerged as a risk factor for cardiovascular disease (CVD) and insulin resistance in the general population. Recently, the prevalence of vitamin D insufficiency and deficiency was recognized to be very high in the US pediatric population and low serum vitamin D were found to be strongly and independently associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity or other CVD risk factors. As HIV-infected children are expected to live several decades, issues of long- term toxicities, such as CVD and diabetes become increasingly important in the management of HIV. The central hypothesis of our proposed studies is that, vitamin D deficiency is a risk factor for the development of subclinical atherosclerosis and insulin resistance in HIV infected children/young adults, and that the risk is mediated by changes in systemic inflammation. To strengthen the findings from the observational study, we will conduct an interventional study, in which we hypothesize that high doses of vitamin D given to HIV-infected children/young adults with low vitamin D levels will increase 25-hydroxyvitamin D (25(OH)D) levels at a lower extent than in a matched healthy HIV-negative control group, specifically in patients treated with NNRTI, and will reduce inflammation, insulin resistance and dyslipidemias. Detailed measures of vitamin D pathways will also be determined. The use of vitamin D has the potential to have a significant impact on prevention of HIV cardiovascular and metabolic co-morbidities especially given that the intervention can be implemented easily and inexpensively in clinical practice.

描述（由申请人提供）：维生素D作为一种强大的免疫调节剂发挥作用，其不足最近已成为普通人群中心血管疾病（CVD）和胰岛素抵抗的风险因素。最近，维生素D不足和缺乏的患病率被认为在美国儿科人群中非常高，低血清维生素D被发现与高血压、高血糖和代谢综合征密切相关，独立于肥胖或其他CVD风险因素。由于预计感染HIV的儿童可以活几十年，长期毒性问题，如CVD和糖尿病在HIV管理中变得越来越重要。我们提出的研究的中心假设是，维生素D缺乏是HIV感染儿童/年轻人发生亚临床动脉粥样硬化和胰岛素抵抗的危险因素，并且该风险是由全身炎症的变化介导的。为了加强观察性研究的结果，我们将进行一项干预性研究，在这项研究中，我们假设给予维生素D水平低的HIV感染儿童/年轻人高剂量的维生素D将以低于匹配的健康HIV阴性对照组的程度增加25-羟基维生素D（25（OH）D）水平，特别是在接受NNRTI治疗的患者中，并将减少炎症，胰岛素抵抗和血脂异常。还将确定维生素D途径的详细措施。维生素D的使用有可能对预防艾滋病毒心血管和代谢合并症产生重大影响，特别是考虑到干预措施可以在临床实践中轻松且廉价地实施。