January 8, 2013

How does breastfeeding protect against HIV?

By Beth Skwarecki
Posted: January 8, 2013

The amazing thing about babies drinking breastmilk from HIV-positive mothers is that they don’t always contract HIV.

Statistics vary, but about 85% of the time, that baby is still HIV-negative when they wean (assuming they were negative at birth). Why? Research has been building up over the last few years to try to tease out the answer to that question, and currently the spotlight is on a family of molecules that are the third-most-abundant in breastmilk (after fat and protein) but that the baby can’t digest: sugar-based oligosaccharides.

OK, I’ll back up. If you’re reading this from a place where clean water is abundant, and formula is available at the grocery store and you have the money to buy it, you may be wondering why it’s an issue at all – why risk that 15% transmission rate when you could just feed the kid formula and not have to worry? Worldwide, that’s often not the case. The WHO’s current guidelines state that formula should be used only when it is accessible, feasible, affordable, sustainable, and safe; but where that’s not guaranteed, mothers should breastfeed if at all possible.

That’s because breastfeeding carries so much protection against other nutritional and infectious diseases that the risk is worth it. Even a study that demonstrated the risks of HIV transmission in breastfeeding had a similar mortality rate between the HIV-positive, breastfed group and the formula feeders who were given free formula and instructed in sanitation.

The ideal situation in developing countries is to pair breastfeeding with antiretroviral drug therapy for both mother and child, which can reduce the rate of transmission to just 1%. (But even without drugs, WHO recommends breastfeeding anyway). South Africa adopted this policy in 2012 with some controversy; the rate of exclusive breastfeeding there is abysmally low. Some studies have shown that combining human milk with other foods – even solid foods in the case of an older baby, or even water – increases the likelihood of transmission from milk. The reason isn’t understood.

Last year, a study in PLOS Pathogens confirmed what both epidemiological and in vitro studies had hinted at: human milk prevents oral transmission of HIV. The authors created “humanized” mice, with bone marrow, liver, and thymus tissue from humans, and thus (as they described it) a “fully functioning human immune system.” They showed that the mice could contract HIV orally, but when the virus was delivered in the presence of human milk (obtained from HIV-negative women), transmission was completely stopped.

Obviously, the story isn’t that simple; it doesn’t account for the transmission that does occur. Calculations put the chance of contracting HIV from breastmilk at .00064 per liter, or .00028 per day of breastfeeding. Milk also varies from mother to mother, and it varies over time, which adds extra challenges to studying what’s going on. Meanwhile, the rate of virus particle shedding, and the form of virus (in or out of cells, for example) can also vary.

A magic ingredient?

Without human milk, infants are effectively missing a piece of their immune system; secretory IgA antibodies, for example, are abundant in milk and act in the infant’s gut. Proteins like lactoferrin have antimicrobial activity. The component that has been highlighted recently as preventing HIV transmission is a family of molecules made of strings of sugars. They’re called Human Milk Oligosaccharides.

Although they are made of sugar, HMOs aren’t digested by the infant.We used to think they must be “prebiotics” consumed by the bacteria that live in the baby’s gut, and that’s often true; one bug, Bifidobacterium infantis, consumes the lion’s share of the short-chain HMOs.

By tailoring the exact mix, moms are selecting particular types of bacteria for their child’s gut, in much the same way you can attract certain birds to your yard by the types of seed you put in your bird feeder. This explains, at least in part, why breastfed babies have dramatically different gut flora than babies that drink formula – even one bottle of formula can change their gut microbiome forever.

But, according to recent research, the protection from HIV may come from a different feature of HMOs: their ability to act as decoy binding sites for HIV.

One of the lesser-known jobs of oligosaccharides is that, in combination with proteins, they can stick out from a virus or cell surface, making a sort of flag that other cells can recognize. In the case of HIV, the virus bears an oligosaccharide that looks for a sugar-binding protein called DC-SIGN on the surface of human intestinal cells. But when decoy oligosaccharides from milk flood the gut, DC-SIGN binds to these instead, keeping the baby’s bloodstream HIV-free … for the moment, anyway.

Recent research has found multiple HMOs that protect against HIV, and at least one that increases risk; but overall, the more HMOs in milk, the smaller the risk of transmitting HIV. Lars Bode, the researcher behind many of the studies I’ve cited here, has written that “remarkably little is known about how, when and where [HMOs] are metabolized.” Human milk contains a complex cast of characters that we are just beginning to understand.

Expect to hear more about this family of molecules; hints from patent searches show that companies are interested in them: as prebiotics, and for protection against infant diseases like necrotizing enterocolitis. In the meantime, this research may lead to new ways of preventing HIV transmission, and confirms breastfeeding as a healthy practice for moms in developing countries.

  1. World Health Organization. 2007. HIV transmission through breastfeeding: a review of available evidence. link
  2. World Health Organization. 2010. Guidelines on HIV and infant feeding 2010. link
  3. Coutsoudis A. Breastfeeding in Women With HIV. JAMA. 2000;284(8):956-957. doi:10.1001/jama.284.8.956. link
  4. Vyankandondera, J., Luchters, S., Hassink, E., Pakker, N., Mmiro, F., Okong, P., … & Lange, J. (2003, July). Reducing risk of HIV-1 transmission from mother to infant through breastfeeding using antiretroviral prophylaxis in infants (SIMBA-study). In 2nd ias conference on hiV pathogenesis and treatment. paris, france (pp. 13-16). news article link

  5. Horvath T, Madi BC, Iuppa IM, Kennedy GE, Rutherford GW, Read JS. Interventions for preventing late postnatal mother-to-child transmission of HIV. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006734. DOI: 10.1002/14651858.CD006734.pub2. link
  6. Wahl A, Swanson MD, Nochi T, Olesen R, Denton PW, et al. (2012) Human Breast Milk and Antiretrovirals Dramatically Reduce Oral HIV-1 Transmission in BLT Humanized Mice. PLoS Pathog 8(6): e1002732. doi:10.1371/journal.ppat.1002732 link
  7. Richardson, B. A., John-Stewart, G. C., Hughes, J. P., Nduati, R., Mbori-Ngacha, D., Overbaugh, J., & Kreiss, J. K. (2003). Breast-milk infectivity in human immunodeficiency virus type 1–infected mothers. Journal of infectious diseases, 187(5), 736-740. link

  8. Hanson, L. A., and T. Söderström. “Human milk: Defense against infection.” Progress in clinical and biological research 61 (1981): 147. link

  9. Harmsen, Martin C., et al. “Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro.” Journal of Infectious Diseases 172.2 (1995): 380-388. link

  10. Asakuma, Sadaki, et al. “Physiology of consumption of human milk oligosaccharides by infant gut-associated bifidobacteria.” Journal of Biological Chemistry 286.40 (2011): 34583-34592. link

  11. Coppa, G. V., et al. “Prebiotics in human milk: a review.” Digestive and Liver Disease 38 (2006): S291-S294. link

  12. Q Zhang, Angela, et al. “Human whey promotes sessile bacterial growth, whereas alternative sources of infant nutrition promote planktonic growth.” Current Nutrition & Food Science 8.3 (2012): 168-176. news article link

  13. Naarding, Marloes A., et al. “Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4^+ T lymphocytes.” Journal of Clinical Investigation 115.11 (2005): 3256. link

  14. Bode, Lars, et al. “Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding.” The American Journal of Clinical Nutrition 96.4 (2012): 831-839. news article link

  15. Jantscher-Krenn, E., and L. Bode. “Human milk oligosaccharides and their potential benefits for the breast-fed neonate.” Minerva pediatrica 64.1 (2012): 83. link


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