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

描述（由申请人提供）：维生素D作为一种强大的免疫调节剂，其不足最近被认为是普通人群心血管疾病（CVD）和胰岛素抵抗的危险因素。最近，维生素D不足和缺乏的患病率在美国儿科人群中被认为非常高，血清维生素D水平低被发现与高血压、高血糖和代谢综合征有很强的独立相关性，与肥胖或其他心血管疾病危险因素无关。由于感染艾滋病毒的儿童预计可以活几十年，长期毒性问题，如心血管疾病和糖尿病，在艾滋病毒的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缺乏是艾滋病毒感染儿童/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，并且这种风险是由全身炎症变化介导的。为了加强观察性研究的发现，我们将进行一项干预性研究，在该研究中，我们假设高剂量的维生素D给予低维生素D水平的hiv感染儿童/年轻人，会比匹配的健康hiv阴性对照组增加25(OH)D （25(OH)D）水平，特别是在接受NNRTI治疗的患者中，并会减少炎症、胰岛素抵抗和血脂异常。还将确定维生素D途径的详细测量方法。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，特别是考虑到在临床实践中可以很容易和廉价地实施干预。

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.