Department of Medicine, University of Washington, Seattle, WA, USA.
AIDS. 2012 Oct 23;26(16):2007-16. doi: 10.1097/QAD.0b013e328359b7e0.
Breast milk is a major route of infant HIV infection, yet the majority of breast-fed, HIV-exposed infants escape infection by unknown mechanisms. This study aimed to investigate the role of HIV-specific breast milk cells in preventing infant HIV infection.
A prospective study was designed to measure associations between maternal breast milk HIV-specific interferon-γ (IFN-γ) responses and infant HIV-1 detection at 1 month of age.
In a Kenyan cohort of HIV-infected mothers, blood and breast milk HIV-gag IFN-γ ELISpot responses were measured. Logistic regression was used to measure associations between breast milk IFN-γ responses and infant HIV infection at 1 month of age.
IFN-γ responses were detected in breast milk from 117 of 170 (69%) women. IFN-γ responses were associated with breast milk viral load, levels of macrophage inflammatory protein (MIP) 1α, MIP-1β, regulated upon activation, normal T-cell expressed, and secreted and stromal-cell derived factor 1 and subclinical mastitis. Univariate factors associated with infant HIV infection at 1 month postpartum included both detection and breadth of breast milk IFN-γ response (P = 0.08, P = 0.04, respectively), breast milk MIP-1β detection (P = 0.05), and plasma (P = 0.004) and breast milk (P = 0.004) viral load. In multivariate analyses adjusting for breast milk viral load and MIP-1β, breast milk IFN-γ responses were associated with an approximately 70% reduction in infant HIV infection [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.092-0.91], and each additional peptide pool targeted was associated with an approximately 35% reduction in infant HIV (aOR 0.65, 95% CI 0.44-0.97).
These data show breast milk HIV-gag-specific IFN-γ cellular immune responses are prevalent and may contribute to protection from early HIV transmission. More broadly, these data suggest breast milk cellular responses are potentially influential in decreasing mother-to-child transmission of viruses.
母乳是婴儿 HIV 感染的主要途径,但大多数母乳喂养、HIV 暴露的婴儿通过未知机制避免了感染。本研究旨在探讨 HIV 特异性母乳细胞在预防婴儿 HIV 感染中的作用。
设计了一项前瞻性研究,以测量产妇母乳中 HIV gag 干扰素-γ(IFN-γ)反应与 1 个月龄婴儿 HIV-1 检测之间的关联。
在肯尼亚的 HIV 感染母亲队列中,测量了血液和母乳中 HIV gag IFN-γ ELISpot 反应。使用逻辑回归来测量母乳 IFN-γ 反应与 1 个月龄婴儿 HIV 感染之间的关联。
在 170 名女性中的 117 名(69%)女性的母乳中检测到 IFN-γ 反应。IFN-γ 反应与母乳病毒载量、巨噬细胞炎性蛋白(MIP)1α、MIP-1β、激活正常 T 细胞表达和分泌、基质细胞衍生因子 1 和亚临床乳腺炎水平相关。产后 1 个月婴儿 HIV 感染的单变量因素包括母乳 IFN-γ 反应的检测和广度(P=0.08,P=0.04)、母乳 MIP-1β 检测(P=0.05)以及血浆(P=0.004)和母乳(P=0.004)病毒载量。在调整母乳病毒载量和 MIP-1β 的多变量分析中,母乳 IFN-γ 反应与婴儿 HIV 感染的降低约 70%相关[调整后的优势比(aOR)0.29,95%置信区间(CI)0.092-0.91],并且靶向的每个额外肽库与婴儿 HIV 的降低约 35%相关[aOR 0.65,95%CI 0.44-0.97]。
这些数据表明母乳 HIV gag 特异性 IFN-γ 细胞免疫反应普遍存在,并可能有助于预防早期 HIV 传播。更广泛地说,这些数据表明母乳细胞反应可能在降低母婴传播病毒方面具有影响力。