Findings published online this August in the American Journal of Clinical Nutrition
found that HIV-infected mothers with high concentrations of human mi
lk oligosaccharides (HMOS)—complex carbohydrates abundant in breast milk—were less likely to transmit HIV to their infants than HIV-infected mothers with lower concentrations of HMOs. The study, led by researchers from the University of California at San Diego and conducted in a cohort of nearly 1,000 HIV-infected women from Zambia, is among a host of studies trying to determine how the mixture of proteins, carbohydrates and lipids that comprise human breast milk may be benefiting the developing immune systems of babies feeding on it. To learn more about this study, VAX
science writer Regina McEnery spoke with Laura Guay, vice president of research at the Elizabeth Glaser Pediatric AIDS Foundation, which provided research support to one of the study authors. Guay also weighed in on the American Academy of Pediatrics (AAP) recent recommendations on infant circumcision and why developing countries have not embraced infant circumcision policies as an easier alternative to adult male circumcision for prevention of later sexual acquisition of HIV in men.
What did scientists set out to do in this study of HMOs?
In this study, scientists were measuring levels of HMOs in breast milk and seeing if there was an association between these [glycans] and HIV transmission. Scientists did not make conclusions about whether these HMOs inhibited or enhanced transmission, just that HIV infected women with higher [overall level] of HMOs seemed to be less likely to transmit HIV to their infant through breastfeeding. But the findings are more subtle than that. When you look at specific HMOs, the levels were actually higher, in some cases, among HIV-transmitting mothers vs. non-transmitting mothers. So these studies are not meant to say we have an answer. What we really need to do is look at these HMOs in more detail and look at the different compositions and different patterns in breast milk of transmitting and non-transmitting women.
How important are these complex sugars to the immune system of infants?
One of the things that is clear is that there are many compounds of all different types in breast milk that are involved in the nutrition of the baby and in their immune protection, particularly in those early months of life when a baby is exposed to all kinds of pathogens for the first time. This includes different types of antibodies and immune factors that all get passed through to the infant. There are even differences in early vs. later breast milk [during infancy]. There is a whole field of active research trying to sort out the complex roles all of the components of breast milk play on the immunology of the infant’s GI [gastrointestinal] tract.
What prompted HIV researchers to look at HMOs?
Except for women on highly active antiretroviral therapy with undetectable viral load, HIV is present in the breast milk of HIV-positive women. We know breastfeeding is a mechanism in transmission of HIV to the child and we are trying to understand how that happens. We also know that many babies breast feed for a long time yet they don’t get HIV-infected. Why? What is the difference and what might be protective or not? Many people are looking at a wide scope of ingredients and trying to determine what compounds with some immune activity are the most common in non-transmitting mothers and whether there is an actual cause and effect. Another study we are funding is screening various peptides and proteins from breast milk and testing to see if they enhance or inhibit HIV. As technology has advanced in the last two decades, we have been able to learn more about what the components of breast milk do.
What have these tools enabled scientists to learn?
Scientists now have the ability to isolate these HMOs and other components of breast milk and study how they interact with the immune system, particularly in the gut and gastro-intestinal tract. This is important, especially in HIV, because the GI tract is a major site of mucosal immunity. So much of mucosal immunology, disease states and susceptibility to infection can be learned by studying areas of inflammation and immune activation occurring in the gut.
What is the breakdown of HIV rates by mother-to-child transmission through breastfeeding or by other routes?
About 10-15% become infected in utero, 60-70% around the time of labor and delivery—which includes very early breastfeeding as it is difficult to sort out the difference between actual delivery and the first few weeks of breastfeeding—and 20-30% during later breastfeeding.
Were any of the HIV-infected mothers in this study receiving antiretroviral therapy?
Women in the study did receive single dose nevirapine to prevent transmission to the child, though most of the moms were recruited [between May 2001 and September 2004] before antiretroviral therapy became available in the public sector.
Why not add HMOs to infant formula?
There are [more than 100] of these naturally occurring HMOs and their immunological components are impossible to translate and manufacture into a formula.
Moving on to circumcision, the AAP, which previously considered infant circumcision not essential to a child’s current well-being, now recommends it. Why the change in stance?
The AAP revisits guidelines periodically and reviews any new information or studies that have come out that could change what those guidelines say. The recent data on adult male circumcision [which was found to cut HIV risk among men by as much as 60% in Africa] may have provoked it. But studies have also shown that the risk of urinary tract infections and some kinds of cancer are also lower with circumcision. They found that the risk of circumcision remains low, so in weighing these factors, the AAP isn’t saying infant circumcision is medically necessary, just that the benefits of circumcision outweigh the risks associated with circumcision.
What about implementing infant circumcision in developing countries?
That’s more difficult and more complicated. There is a strong belief that to get the biggest effect of male circumcision in preventing sexual acquisition of HIV, you have to get men or young boys [circumcised] before they start sexual activity, so infant male circumcision would be the best method. But so much of the challenge of circumcision [in developing countries] comes down to infrastructure. Even the AAP said the procedure is well tolerated if it is performed by trained professionals under sterile conditions in proper facilities with appropriate pain management. In places that can do it, that is great and some countries are promoting it. But it’s not a simple transition in many places where there are many home deliveries or births in facilities with minimally trained staff and poor infrastructure. And in Africa, there are also cultural traditions related to circumcision that have to be considered.