IMPACT OF MICRONUTRIENTS ON PROGRESSION OF SIV

微量营养素对 SIV 进展的影响

• 批准号: 6330639
• 负责人: SHERWOOD GORBACH
• 金额: $ 37.69万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330639
• 关键词: AIDS therapy; CD4 molecule; Macaca mulatta; body weight; cachexia; dietary supplements; malnutrition; nonhuman therapy evaluation; opportunistic infections; pathologic process; selenium; simian immunodeficiency virus; vitamin B12; vitamin B12 deficiency; weight loss

DESCRIPTION : (duplicated from the abstract provided) Studies in patients with HIV infection have revealed that serum micronutrient levels are often below normal levels particularly for vitamins A, B12, E and for selenium. Some studies have correlated low micronutrient levels with more rapid progression of HIV infection. Intervention trials with micronutrients are extremely difficult to carry out in persons with HIV for the following reasons : a large percentage of HIV/AIDS patients are already taking nutritional supplements in an uncontrolled manner, some in large doses; intake of micronutrients in food varies greatly among persons with HIV infection; there are complex ethical issues surrounding a placebo controlled trial of micronutrients in the HIV/AIDS population; it would be difficult to maintain a micronutrient intervention study during the years of progression of HIV infection; and current and rapidly changing anti-retroviral therapies will alter the natural history of HIV, making it complex to separate out the effects of micronutrient intervention. Yet, micronutrient supplements might play an important role in improving overall nutritional status and slowing the progression of HIV infection. The Simian immunodeficiency virus (SIV) produces an infection in juvenile rhesus monkeys that is remarkably similar to that caused by HIV in humans including, as we have found recently, serum micronutrient deficiencies despite an apparently adequate intake. SIV also causes a wasting condition similar to that seen in young persons with HIV. Because of the rapid progression in SIV, and the clear end points of nutritional parameters, biological markers, and survival, as well as a controlled dietary intake, the SIV-infected rhesus monkey is an ideal model to examine the potential benefit of micronutrient supplementation. To this end we plan to: 1) document the course of micronutrient deficiency and weight loss in SIV-infected juvenile rhesus macaques compared to age matched uninfected control animals; and 2) conduct 3 interventions with micronutrients in SIV infected macaques, including a high supplementation with vitamins and trace minerals; single supplementation with vitamin B12 intramuscularly; and a single supplementation selenium. End points include time of death; body weight and lean body mass; serum micronutrients; viral load; CD4 cell count; and development of opportunistic infections. These studies will allow the evaluation of the efficacy of micronutrient supplements in the monkey SIV model without the confounding factors involved in a study in human HIV infection. In addition, the natural history of nutritional deficits and wasting would be defined in this model, which would provide a basis for further studies on nutritional interventions.

描述：（从提供的摘要中复制） 对 HIV 感染者的研究表明，血清 微量营养素水平通常低于正常水平，特别是 维生素 A、B12、E 和硒。一些研究显示相关性较低 微量营养素水平与艾滋病毒感染进展更快。 微量营养素的干预试验极难进行 由于以下原因，艾滋病毒感染者中的大部分人都被排除在外： 的艾滋病毒/艾滋病患者已经开始服用营养补充剂 不受控制的方式，有些是大剂量的；微量营养素的摄入量 艾滋病毒感染者的食物差异很大；有复杂的 围绕微量营养素安慰剂对照试验的伦理问题 艾滋病毒/艾滋病人群；将很难维持 HIV进展期间的微量营养素干预研究 感染;以及当前和快速变化的抗逆转录病毒疗法 将改变艾滋病毒的自然史，使分离变得复杂 微量营养素干预的效果。然而，微量营养素 补充剂可能在改善整体水平方面发挥重要作用 营养状况并减缓艾滋病毒感染的进展。这 猿猴免疫缺陷病毒（SIV）在幼年动物中引起感染 恒河猴的情况与艾滋病毒引起的情况非常相似 正如我们最近发现的，人类包括血清微量营养素 尽管摄入量明显充足，但仍存在缺陷。 SIV 还会导致 消瘦状况与感染艾滋病毒的年轻人相似。 由于 SIV 的快速进展以及明确的终点 营养参数、生物标记和存活率，以及 控制饮食摄入量，感染 SIV 的恒河猴是理想的选择 模型来检查微量营养素补充的潜在益处。 为此，我们计划：1）记录微量营养素的过程 感染 SIV 的幼年恒河猴的缺乏症和体重减轻 与年龄匹配的未感染对照动物相比； 2) 进行 3 对感染 SIV 的猕猴进行微量营养素干预，包括 大量补充维生素和微量矿物质；单身的 肌肉注射补充维生素B12；和一个单一的 补充硒。终点包括死亡时间；体重 和去脂体重；血清微量营养素；病毒载量； CD4细胞计数； 和机会性感染的发展。 这些研究将有助于评估微量营养素的功效 没有混杂因素的猴 SIV 模型中的补充剂 参与人类艾滋病毒感染的研究。此外，自然 营养缺乏和浪费的历史将在此定义 模型，为进一步的营养研究提供基础 干预措施。