Feasibility study of LGG in HIV-exposed, breastfeeding infants in Tanzania.

描述（由申请人提供）：尽管有证据表明益生菌可以改善胃肠道炎症并调节粘膜表面的免疫防御，但实际上对其影响儿科人群中 HIV-1 传播的潜力一无所知。在撒哈拉以南非洲地区，2004年儿童中新感染HIV-1的人数超过70万人；其中三分之一到二分之一的感染是通过母乳喂养获得的。流行病学研究表明，与纯母乳喂养的婴儿相比，摄入感染 HIV 的母乳和补充食品或液体的婴儿传播 HIV-1 的风险明显更高。虽然其潜在机制尚不清楚，但据推测，接触外来食物抗原或肠道病原体后，新生儿肠道中会诱导炎症反应，从而增加粘膜通透性，从而促进 HIV-1 的渗透和复制。拟议的项目将确定对益生菌乳杆菌 GG (LGG) 作为饮食干预措施进行随机、双盲对照研究的可行性，以减少通过母乳喂养和混合喂养方式接触 HIV-1 的婴儿的胃肠道炎症。这项研究将与莫辛比利大学健康科学学院合作在坦桑尼亚达累斯萨拉姆进行。我们将验证以下假设：给暴露于 HIV 的母乳喂养婴儿口服添加 LGG 的粥可以减少肠粘膜炎症，并有可能降低 HIV-1 传播的风险。我们将通过两个具体目标来解决这一假设：第一个目标是确定在传统玉米粥中向随机接受此干预的婴儿施用 LGG 的可行性，第二个目标是确定补充 LGG 的粥在减少胃肠道炎症和肠道病原体定植方面的有效性。该研究的主要结果是肠道炎症的两种粪便生物标志物 TNF-α 和钙卫蛋白的水平降低。次要结果是能够收集有关婴儿喂养方式和接触肠道病原体的支持性数据，并评估母亲 HIV-1 病毒载量和婴儿 HIV-1 状态。总而言之，这些数据将用于指导在暴露于 HIV 的母乳喂养婴儿中开展 LGG 大规模临床试验，以确定这种干预措施在减少 HIV-1 母婴传播方面的功效。如果有效，LGG 的益生菌干预有可能显着减少因感染 HIV-1 和其他传染性肠道病原体而导致的婴儿死亡。利用传统食品输送益生菌提供了一种经济实惠、文化上可接受且易于再生的干预措施，并且适合在撒哈拉以南非洲资源有限的国家使用。

DESCRIPTION (provided by applicant): Despite evidence probiotics can ameliorate gastrointestinal inflammation and modulate immune defenses at mucosal surfaces, virtually nothing is known of their potential to impact transmission of HIV-1 in pediatric populations. In Sub-Saharan Africa, the rate of new HIV-1 infections among children exceeded 700,000 in 2004; from one-third to one-half of these infections were acquired by breastfeeding. Epidemiologic studies indicate that infants ingesting both HIV-infected breast milk and supplemental foods or fluids are at significantly higher risk of HIV-1 transmission compared to their exclusively breastfed counterparts. While the underlying mechanism(s) for this are unknown, it is presumed that induction of inflammatory responses in the newborn gut following exposure to foreign food antigens or enteric pathogens increases mucosal permeability, thereby facilitating HIV-1 penetration and replication. The proposed project will determine the feasibility of conducting a randomized, double-blinded controlled study of the probiotic Lactobacillus GG (LGG) as a dietary intervention to reduce gastrointestinal inflammation in infants exposed to HIV-1 through breastfeeding and mixed-feeding practices. This study will be conducted in Dar es Salaam, Tanzania in collaboration with Muhimbili University College of Health Sciences. We will test the hypothesis that oral administration of LGG-supplemented porridge to HIV-exposed, breastfeeding infants reduces intestinal mucosal inflammation and has the potential decrease the risk of HIV-1 transmission. We will address this hypothesis through two specific aims: the first to determine the feasibility of administering LGG in a traditional maize porridge to infants randomized to this intervention, and the second to determine the effectiveness of LGG-supplemented porridge in reducing gastrointestinal inflammation and colonization with enteric pathogens. The primary outcome of the study is a reduction in the levels of two fecal biomarkers for intestinal inflammation, TNF-alpha and calprotectin. Secondary outcomes are the ability to collect supportive data on infant feeding practices and exposure to enteropathogens, and to assess maternal HIV-1 viral load and infant HIV-1 status. Taken together, these data will be used to guide the development of a large-scale clinical trial of LGG in HIV-exposed, breastfeeding infants to determine the efficacy of this intervention in reducing HIV-1 mother-to-child transmission. If effective, probiotic intervention with LGG has the potential to significantly reduce infant deaths due to infection with HIV-1 and other infectious enteric pathogens. Utilizing a traditional food for probiotic delivery provides an intervention that is affordable, culturally accepted and readily renewable, and would be amenable for use in resource-constrained countries in Sub-Saharan Africa.