Van de Perre P, Simonon A, Hitimana D G, Dabis F, Msellati P, Mukamabano B, Butera J B, Van Goethem C, Karita E, Lepage P
National AIDS Control Programme, AIDS Reference Laboratory, Kigali, Rwanda.
Lancet. 1993 Apr 10;341(8850):914-8. doi: 10.1016/0140-6736(93)91210-d.
Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly by cell-to-cell contact. We postulated that transmission of HIV-1 through breastmilk could be favoured by the presence of infected cells, by deficiency of anti-infective substances in breastmilk, or both factors. 215 HIV-1-infected women were enrolled at delivery in Kigali, Rwanda; milk samples were collected 15 days, 6 months, and 18 months post partum. HIV-1 IgG, secretory IgA, and IgM were assayed by western blot, for the latter two after removal of IgG with protein G. In the 15-day and 6-month samples, we sought viral genome in milk cells by a double polymerase chain reaction with three sets of primers (gag, pol, and env). HIV-1 infection in the offspring was defined according to serological and clinical criteria. At 15 days, 6 months, and 18 months post partum, HIV-1 specific IgG was detected in 95%, 98%, and 97% of breastmilk samples, IgA in 23%, 28%, and 41%, and IgM in 66%, 78%, and 41%. In children who survived longer than 18 months, the probability of infection was associated with lack of persistence of IgM and IgA in their mothers' milk (adjusted chi 2 for trend, p = 0.01 for IgM and p = 0.05 for IgA). The presence of HIV-1-infected cells in the milk 15 days post partum was strongly predictive of HIV-1 infection in the child, by both univariate (p < 0.05) and multivariate analysis (p = 0.01). The combination of HIV-1-infected cells in breastmilk and a defective IgM response was the strongest predictor of infection. HIV-1 infection in breastfed children born to infected mothers is associated with the presence of integrated viral DNA in the mothers' milk cells. IgM and IgA anti-HIV-1 in breastmilk may protect against postnatal transmission of the virus.
1型人类免疫缺陷病毒（HIV-1）主要通过细胞间接触传播。我们推测，母乳中存在受感染细胞、母乳中抗感染物质缺乏或这两种因素共同作用，可能有利于HIV-1通过母乳传播。215名感染HIV-1的妇女在卢旺达基加利分娩时登记入组；产后15天、6个月和18个月采集乳汁样本。采用蛋白质印迹法检测HIV-1 IgG、分泌型IgA和IgM，后两者在使用蛋白G去除IgG后进行检测。在产后15天和6个月的样本中，我们通过使用三组引物（gag、pol和env）的双重聚合酶链反应在乳汁细胞中寻找病毒基因组。根据血清学和临床标准定义子代中的HIV-1感染。产后15天、6个月和18个月时，分别在95%、98%和97%的母乳样本中检测到HIV-1特异性IgG，在23%、28%和41%的样本中检测到IgA，在66%、78%和41%的样本中检测到IgM。在存活超过18个月的儿童中，感染概率与母乳中IgM和IgA缺乏持续性有关（趋势调整卡方检验，IgM为p = 0.01，IgA为p = 0.05）。产后15天乳汁中存在HIV-1感染细胞，单因素分析（p < 0.05）和多因素分析（p = 0.01）均强烈预测儿童感染HIV-1。母乳中HIV-1感染细胞与缺陷性IgM反应相结合是感染的最强预测因素。感染母亲所生母乳喂养儿童中的HIV-1感染与母乳细胞中整合病毒DNA的存在有关。母乳中的IgM和抗HIV-1 IgA可能预防病毒的产后传播。
