Role of Intestinal Mucosal Integrity in HIV Transmission to Infants Through Breast-feeding: The BAN Study
Role of Intestinal Mucosal Integrity in HIV Transmission to Infants Through Breast-feeding: The BAN Study
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DOI：
10.1093/infdis/jit221
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发表时间：
2013-08-15
影响因子：
6.4
通讯作者：
Jamieson, Denise J.
中科院分区：
文献类型：
--
作者：
Kourtis, Athena P.;Ibegbu, Chris C.;Jamieson, Denise J.
背景。肠道通透性增加可能是人类免疫缺陷病毒（HIV）通过母乳喂养传播给婴儿的机制之一。肠道通透性与微生物易位相关，可以通过细菌脂多糖 (LPS) 的定量来测量。方法。我们评估了母乳喂养、抗逆转录病毒和营养 (BAN) 研究中接触但未感染 HIV 的婴儿和感染 HIV 的婴儿的系列样本中的血浆 LPS 水平（通过鲎变形细胞裂解物测定）和免疫激活标记物。结果。 BAN 研究中的婴儿在 24 周龄断奶后，血浆 LPS 水平升高。复方新诺明预防与较高的血浆 LPS 水平相关 (P = .004)。与未感染的婴儿相比，感染 HIV 的婴儿的 LPS 水平较高 (P = .004)。较高的感染前血浆 LPS 水平是婴儿通过母乳喂养感染 HIV 的显着预测因素（血浆 LPS 水平每增加一个单位，风险比 = 1.60；P = .01）和较低的婴儿年龄别身长 z 评分（P = .02）。结论。这些发现表明，肠道完整性的破坏是艾滋病毒通过母乳喂养传播给婴儿的机制。断奶和使用抗生素预防与微生物易位水平增加有关，这可能会促进艾滋病毒通过肠道进入。增强婴儿肠粘膜完整性的补充方法可能会进一步减少艾滋病毒的母乳喂养传播。
Background. Increased intestinal permeability may be one of the mechanisms of transmission of human immunodeficiency virus (HIV) to infants through breast-feeding. Intestinal permeability correlates with microbial translocation, which can be measured through quantification of bacterial lipopolysaccharide (LPS).Methods. We evaluated levels of plasma LPS (by the Limulus amebocyte lysate assay) and immune activation markers in serial specimens from infants exposed to but uninfected with HIV and infants infected with HIV from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study.Results. Plasma LPS levels increased after infants in the BAN study were weaned from the breast, at 24 weeks of age. Cotrimoxazole prophylaxis was associated with higher plasma LPS levels (P = .004). Infants with HIV infection had higher LPS levels, compared with uninfected infants (P = .004). Higher preinfection plasma LPS levels were a significant predictor of infant HIV infection through breast-feeding (hazard ratio = 1.60 for every unit increase in plasma LPS level; P = .01) and of lower infant length-for-age z scores (P = .02).Conclusions. These findings suggest that disruption in intestinal integrity is a mechanism of HIV transmission to infants through breast-feeding. Weaning from breast milk and use of antibiotic prophylaxis was associated with increased levels of microbial translocation, which could facilitate HIV entry through the intestine. Complementary approaches to enhance intestinal mucosal integrity in the infant may further reduce breast-feeding transmission of HIV.