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Athena P. Kourtis, Chris C. Ibegbu, Jeffrey Wiener, Caroline C. King, Gerald Tegha, Deborah Kamwendo, Jacob Kumwenda, Surinder P. Kaur, Valerie Flax, Sascha Ellington, Zebrone Kacheche, Dumbani Kayira, Charles Chasela, Charles van der Horst, Denise J. Jamieson, Role of Intestinal Mucosal Integrity in HIV Transmission to Infants Through Breast-feeding: The BAN Study, The Journal of Infectious Diseases, Volume 208, Issue 4, 15 August 2013, Pages 653–661, https://doi.org/10.1093/infdis/jit221
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Abstract
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.