Impact of Micronutrients on Progression of SIV

描述（由申请人提供）：在HIV感染患者中进行的研究 揭示了血清微量营养素水平经常低于正常水平， 特别是维生素A、B约2和E，以及硒和锌。 一些研究将低微量营养素水平与更快的 HIV感染的进展。我们在SIVmac 239感染恒河猴中的初步研究 猴子的血清中维生素B12、维生素E和硒的水平较低。正在进行 高补充（HS）维生素/微量营养素干预的研究， SIV感染的动物体重和体脂的减少率降低 与安慰剂对照相比。对于此次竞争性续约，我们计划进行 两个阶段的调查：1）单一干预超过36个月， 在该SIV感染模型中肌肉注射维生素B 12和 口服硒，人类研究中最有前途的两种微量营养素;以及2） 在SIV感染者中进行为期36个月的HS维生素/微量营养素干预 接受HAART（PMPA、ddI、羟基脲）的抗逆转录病毒方案的猕猴， 它已经被证明可以产生无法检测到的SIV病毒载量。初级端 两项研究的要点是死亡时间和体重变化。二次 终点是血清微量营养素的测量;瘦体重的变化 (by DEXA、生物电阻抗[BIA]和躯体测量）; SIV 病毒载量; CD 4细胞计数;以及机会性感染的发生。研究 1将显示，如果一个单一的微量营养素，如B 12或硒可以产生 对终点的影响与合并的HS制剂相似。研究2将 模拟在可能患有艾滋病的艾滋病毒/艾滋病患者中使用HAART的情况 尽管血浆病毒载量受到抑制，但体重仍持续减轻， 如果HS维生素/微量营养素干预可以维持体重并改善 营养状况

DESCRIPTION (provided by applicant): Studies in HIV-infected patients have revealed that serum micronutrient levels are often below normal levels, particularly for vitamins A, B about2, and E, as well as for selenium and zinc. Some studies have correlated low micronutrient levels with more rapid progression of HIV infection. Our initial studies in SIVmac239-infected rhesus monkeys have shown low serum levels of Vitamins B12 and E and selenium. Ongoing studies with a highly supplemented (HS) vitamin/micronutrient intervention in SIV-infected animals show a decrease in the rate of loss of weight and body fat compared to placebo controls. For this competitive renewal, we plan to conduct two phases of investigations: 1) single interventions over 36 months of observation in this SIV- infected model with intramuscular Vitamin B 12 and oral selenium, the two most promising micronutrients in human studies; and 2) Conduct an HS vitamin/micronutrient intervention over 36 months in SIV-infected macaques receiving an antiretroviral regimen of HAART (PMPA, ddI, hydroxyurea), which has been shown to produce undetectable SIV viral loads. Primary end points for both studies are time of death and changes in body weight. Secondary end points are measurements of serum micronutrients; changes in lean body mass (by DEXA, bioelectric impedance [BIA], and somatometric measurements); SIV viral load; CD4 cell count; and development of opportunistic infections. Study 1 will show if a single micronutrient such as B 12 or selenium can produce similar effects on end points as the combined HS preparations. Study 2 will simulate the situation of using HAART in HIV/AIDS patients who may have continued weight loss despite suppression of plasma viral load, in order to see if the HS vitamin/micronutrient intervention can maintain weight and improve nutritional status.