Mehta Saurabh, Fawzi Wafaie
Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, Massachusetts 02115, USA.
Vitam Horm. 2007;75:355-83. doi: 10.1016/S0083-6729(06)75013-0.
An estimated 25 million lives have been lost to acquired immune-deficiency syndrome (AIDS) since the immunodeficiency syndrome was first described in 1981. The progress made in the field of treatment in the form of antiretroviral therapy (ART) for HIV disease/AIDS has prolonged as well as improved the quality of life of HIV-infected individuals. However, access to such treatment remains a major concern in most parts of the world, especially in the developing countries. Hence, there is a constant need to find low-cost interventions to complement the role of ART in prevention of HIV infection and slowing clinical disease progression. Nutritional interventions, particularly vitamin supplementation, have the potential to be a low-cost method for being such an intervention by virtue of their modulation of the immune system. Among all the vitamins, the role of vitamin A has been studied most extensively; most observational studies have found that low vitamin A levels are associated with increased risk of transmission of HIV from mother to child. This finding has not been supported by large randomized trials of vitamin A supplementation; on the contrary, these trials have found that vitamin A supplementation increases the risk of mother-to-child transmission (MTCT). There are a number of potential mechanisms that might explain these contradictory findings. One is the issue of reverse causality in observational studies-for instance, advanced HIV disease may suppress release of vitamin A from the liver. This would lead to low levels of vitamin A in the plasma despite the body having enough vitamin A liver stores. Further, advanced HIV disease is likely to increase the risk of MTCT, and hence it would appear that low serum vitamin A levels are associated with increased MTCT. The HIV genome also has a retinoic acid receptor element-hence, vitamin A may increase HIV replication via interacting with this element, thus increasing risk of MTCT. Finally, vitamin A is known to increase lymphoid cell differentiation, which leads to an increase in CCR5 receptors. These receptors are essential for attachment of HIV to the lymphocytes and therefore, an increase in their number is likely to increase HIV replication. Vitamin A supplementation in HIV-infected children, on the other hand, has been associated with protective effects against mortality and morbidity, similar to that seen in HIV-negative children. The risk for lower respiratory tract infection and severe watery diarrhea has been shown to be lower in HIV-infected children supplemented with vitamin A. All-cause mortality and AIDS-related deaths have also been found to be lower in vitamin A-supplemented HIV-infected children. The benefits of multivitamin supplementation, particularly vitamins B, C, and E, have been more consistent across studies. Multivitamin supplementation in HIV-infected pregnant mothers has been shown to reduce the incidence of adverse pregnancy outcomes such as fetal loss and low birth weight. It also has been shown to decrease rates of MTCT among women who have poor nutritional or immunologic status. Further, multivitamin supplementation reduces the rate of HIV disease progression among patients in early stage of disease, thus delaying the need for ART by prolonging the pre-ART stage. In brief, there is no evidence to recommend vitamin A supplementation of HIV-infected pregnant women; however, periodic vitamin A supplementation of HIV-infected infants and children is beneficial in reducing all-cause mortality and morbidity and is recommended. Similarly, multivitamin supplementation of people infected with HIV, particularly pregnant women, is strongly suggested.
自1981年首次描述免疫缺陷综合征以来,估计已有2500万人死于获得性免疫缺陷综合征(艾滋病)。以抗逆转录病毒疗法(ART)治疗HIV疾病/艾滋病的形式在治疗领域取得的进展延长了HIV感染者的生命并改善了其生活质量。然而,在世界大部分地区,尤其是发展中国家,获得这种治疗仍然是一个主要问题。因此,一直需要寻找低成本的干预措施来补充ART在预防HIV感染和减缓临床疾病进展方面的作用。营养干预,特别是维生素补充,由于其对免疫系统的调节作用,有可能成为一种低成本的干预方法。在所有维生素中,维生素A的作用研究最为广泛;大多数观察性研究发现,维生素A水平低与母婴传播HIV的风险增加有关。这一发现并未得到维生素A补充剂大型随机试验的支持;相反,这些试验发现维生素A补充剂会增加母婴传播(MTCT)的风险。有许多潜在机制可以解释这些相互矛盾的发现。一是观察性研究中的反向因果关系问题——例如,晚期HIV疾病可能会抑制肝脏中维生素A的释放。这将导致血浆中维生素A水平降低,尽管体内肝脏储存有足够的维生素A。此外,晚期HIV疾病可能会增加MTCT的风险,因此似乎血清维生素A水平低与MTCT增加有关。HIV基因组也有一个视黄酸受体元件——因此,维生素A可能通过与该元件相互作用增加HIV复制,从而增加MTCT的风险。最后,已知维生素A会增加淋巴细胞分化,从而导致CCR5受体增加。这些受体对于HIV附着于淋巴细胞至关重要,因此,其数量增加可能会增加HIV复制。另一方面,在感染HIV的儿童中补充维生素A与降低死亡率和发病率的保护作用有关,这与在未感染HIV的儿童中观察到的情况类似。已证明,补充维生素A的感染HIV的儿童下呼吸道感染和严重水样腹泻的风险较低。在补充维生素A的感染HIV的儿童中,全因死亡率和与艾滋病相关的死亡也较低。多种维生素补充剂,特别是维生素B、C和E的益处,在各项研究中更为一致。在感染HIV的孕妇中补充多种维生素已被证明可降低不良妊娠结局的发生率,如流产和低出生体重。还已证明,这可降低营养或免疫状况较差的妇女中的MTCT率。此外,多种维生素补充剂可降低疾病早期患者中HIV疾病进展的速率,从而通过延长ART前阶段来推迟对ART的需求。简而言之,没有证据推荐对感染HIV的孕妇补充维生素A;然而,定期对感染HIV的婴儿和儿童补充维生素A有利于降低全因死亡率和发病率,因此是推荐的。同样,强烈建议对感染HIV的人,特别是孕妇补充多种维生素。