Safe and Effective Vitamin D Supplementation in HIV

描述（由申请人提供）：维生素D （vit D）在维持最佳骨骼健康方面的关键作用早已被认识到，但它在调节先天免疫反应和炎症反应方面的作用直到最近才得到积极的研究。因此，维生素D被越来越频繁地选择和规定为高剂量膳食补充剂，因为它被认为可以改善所有年龄段的健康人以及患有慢性疾病（包括艾滋病毒/艾滋病）的人的免疫和炎症状况。维生素D还具有对骨骼健康至关重要的钙化功能，维生素D水平低下会导致抗逆转录病毒治疗（ART）相关的骨质减少/骨质疏松症。维生素D可以改善胰岛素/葡萄糖/脂质代谢、血压和某些癌症的风险，所有这些都可能使艾滋病毒/艾滋病及其治疗复杂化。维生素D水平低下在所有年龄段的HIV/AIDS患者中都很常见，年龄、皮肤色素、乳糖不耐症和阳光照射等因素会改变维生素D缺乏的风险。在多中心的美国REACH研究中（72%的非裔美国人），无论是否感染艾滋病毒，87%的人血清25-羟基维生素D3 （25D）浓度低（<15 ng/mL），而最近来自费城的健康非裔美国儿童样本中这一比例为34%。在美国，年轻的非洲裔美国人受到艾滋病毒感染的影响不成比例（在13至24岁的艾滋病毒感染者中，约55%是非洲裔美国人），并且维生素D缺乏症的风险也很高。维生素D治疗有很大的希望改善主要的医疗条件和生活质量为我们的艾滋病毒/艾滋病患者，但维生素D在治疗艾滋病毒/艾滋病的潜在作用尚未正式测试。迫切需要精心设计的随机试验来确定维生素D补充的安全性和有效性。研究人员提出了一项两阶段的研究，以确定高剂量维生素D补充剂对儿童和成人艾滋病毒/艾滋病患者的安全性和有效性。在研究I期，在44名年龄在5.0至24.9岁的受试者中，在12周内确定了两种口服维生素D3剂量（4000和7000 IU/d）的安全性和有效性。关键的安全措施是同时提高血清钙和25D浓度。通过血清25D浓度和抗菌蛋白（cathelicidin，先天免疫、抗菌蛋白）mRNA表达来评价疗效。研究II期是一项为期12个月、双盲、随机、安慰剂对照的补充研究（n=52）。主要结局包括在目标范围内（32至160 ng/mL）的安全性和长期25D浓度，改善的儿茶素mRNA表达，以及骨骼、肌肉、炎症、生长和身体成分状态以及HIV/AIDS疾病严重程度的测量。基于证据和前景，维生素D显然应该成为国家补充和替代医学中心（NCCAM）艾滋病研究项目评估的首批营养素之一。

DESCRIPTION (provided by applicant): The key role of vitamin D (vit D) in maintaining optimal bone health has long been recognized, but its role in modulating the innate immune response and inflammatory reaction has only recently come under active investigation. As such, vit D is an increasingly frequently chosen and prescribed high dose dietary supplement, because it is thought to improve immune and inflammatory status in healthy people of all ages, and in those with chronic diseases including HIV/AIDS. Vit D also has calciotrophic functions essential for bone health, and poor vit D status contributes to the osteopenia/osteoporosis associated with antiretroviral therapy (ART). Vit D may improve insulin/glucose/lipid metabolism, blood pressure, and risk of some cancers, all of which may complicate HIV/AIDS and its treatments. Poor vit D status is common in HIV/AIDS patients of all ages and factors such as age, skin pigment, lactose intolerance, and sun exposure alter the risks for vit D deficiency. In the multicenter U.S. REACH study of adolescents (72% African American), with and without HIV, showed that 87% had low serum 25-hydroxyvitamin D3 (25D) concentrations (<15 ng/mL), compared to 34% in a recent sample of healthy African American children from Philadelphia. Young African Americans are disproportionately affected by HIV infection in the US (~ 55% among persons with HIV aged 13 to 24 years are African American), and are also at high risk for vit D deficiency. Vit D therapy has great promise to improve major medical conditions and the quality of life for our HIV/AIDS patients, yet the potential role of vitamin D in the treatment of HIV/AIDS has not been formally tested. Well-designed randomized trials are urgently needed to determine vit D supplementation safety and efficacy. The investigators propose a two-phase study to establish safety and efficacy of high dose vit D supplementation in children and adults with HIV/AIDS. In Study Phase I, the safety and efficacy of two oral vit D3 doses (4000 and 7000 IU/d) are determined over 12 weeks in 44 subjects ages 5.0 to 24.9 years. The key safety measure is concurrently elevated serum calcium and 25D concentrations. Efficacy is evaluated by serum 25D concentration and cathelicidin (innate immune, antimicrobial protein) mRNA expression. Study Phase II is a 12 month, double blind, randomized, placebo controlled supplementation study (n=52). Key outcomes include safety and long- term 25D concentration within the goal range (32 to 160 ng/mL), improved cathecidin mRNA expression, and measures of bone, muscle, inflammation, growth and body composition status, and HIV/AIDS disease severity. Based on the evidence and promise, vit D clearly deserves to be among the first nutrients evaluated in the National Center for Complimentary and Alternative Medicine (NCCAM) HIV research program. PUBLIC HEALTH RELEVANCE: Optimal vitamin D concentration and metabolism are essential for normal immune function, growth, muscle, bone, and inflammatory status in children, adolescents and adults with HIV/AIDS. The impact of vitamin D supplementation will be evaluated for safety and efficacy using clinically important outcomes, and this will overcome the critical barrier for use of vitamin D supplementation in research and clinical care. Inexpensive and easy to administer, vitamin D supplementation may prove to be an effective and feasible treatment for symptoms and prevention of side effects for people of all ages living with HIV/AIDS in the US and around the world.