Impact of Micronutrients on Progression of SIV

描述(由申请者提供)：对艾滋病毒感染者的研究 据透露，血清微量营养素水平经常低于正常水平， 尤其是维生素A、B和E，以及硒和锌。 一些研究已经将低微量营养素水平与更快的 艾滋病毒感染的进展。SIVmac239感染恒河猴的初步研究 猴子的血清维生素B12、维生素E和硒水平较低。正在进行中 高水平补充(HS)维生素/微量营养素干预的研究 感染SIV的动物体重和体脂减少率降低。 与安慰剂对照组相比。对于这次竞争性更新，我们计划进行 调查的两个阶段：1)超过36个月的单一干预 肌肉注射维生素B_(12)和维生素B_(12)对SIV感染模型的观察 口服硒，人体研究中最有前途的两种微量营养素；和2) 对感染SIV的患者进行超过36个月的HS维生素/微量营养素干预 接受HAART(PMPA、DDI、羟基脲)抗逆转录病毒疗法的猕猴， 它已被证明会产生无法检测到的SIV病毒载量。主端 这两项研究的重点都是死亡时间和体重变化。次要的 终点是对血清微量营养素的测量；瘦体重的变化 (通过DEXA、生物电阻抗[BIA]和人体测量)；SIV 病毒载量；CD4细胞计数；以及机会性感染的发展。学习 1将显示一种微量营养素，如B12或硒是否能产生 对终点的影响与HS联合制剂相似。研究2将 模拟HIV/AIDS患者使用HAART的情况 尽管血浆病毒载量受到抑制，但体重仍在继续下降，以便看到 HS维生素/微量营养素干预是否能保持体重并改善 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.