Breastfeeding can account for up to 39% of pediatric HIV infections. In developed countries, HIV-infected mothers feed formula to their infants to prevent postpartum HIV transmission. However, in many parts of the developing world, formula is unaffordable and is associated with high morbidity and mortality due to infectious diseases such as gastroenteritis and malnourishment. Therefore, the current WHO guidelines recommend that HIV-infected mothers from most underdeveloped settings breastfeed their infants. Multiple observational, prospective studies have shown that exclusive breastfeeding (EBF) reduces the risk of mother-to-child- transmission (MTCT) two to tenfold compared to infants that are mixed-fed (MF) with other milks, liquids, or solids in addition to breast. EBF decreases morbidity even in non-HIV-exposed infants in both developed and developing settings. EBF decreases morbidity even in non-HIV-exposed infants in both developed and developing settings. However, EBF is difficult for mothers to maintain, and infants are given complementary foods after four to six months of age. In addition, a study of EBF with rapid weaning at four months showed high morbidity in the uninfected infants. Understanding the mechanisms associated with this increased risk could lead to interventions to make mixed feeding and complementary feeding safer for infants. One potential explanation for the protective effect of EBF is that the addition of non-breast milk liquids and solids alters the infant's mucosal or immunologic barriers of the upper gastrointestinal tract. This could lead to immune cell activation with an increase HIV target cells at the mucosa, or increased microbial translocation across the gut, possibly due to compromised mucosal integrity or increased gastrointestinal and/or systemic infections. This project tests the hypothesis that mixed fed infants will display evidence for immune activation within both mucosal and systemic compartments when compared to EBF infants (Aim 1), by measuring immune activation in the blood and in saliva of infants with different feeding practices. This increase in immune activation could be due to changes in the gut commensal organisms in early life (Aim 2). Therefore, these experiments will analyze the microbes in stool of these babies. This activation is possibly derived from mixed feeding- induced mucosal impairment or infections and the consequent translocation of bacterial products across the gut mucosa into the systemic circulation (Aim 3), therefore our experiments will measure microbial products in blood. Through assessment of these infants at multiple time points (6 and 14 weeks of age), this study plans to evaluate the mechanisms conferring EBF infants a reduced risk of HIV infection, and to uncover targets for MTCT prevention during mixed feeding, and to potentially benefit all infants globally who cannot EBF.

Public Health Relevance

These studies are designed to mechanistically discern why HIV transmission is increased in mixed fed infants. These data have the potential to lead to future studies of interventions to prevent postpartum MTCT, such as specific immune interventions to down-modulate the numbers of target cells or through targeted gut microbial therapies through the use of probiotic supplementation for mixed fed infants.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Raiten, Daniel J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Seattle Biomedical Research Institute
United States
Zip Code
Lennard, Katie; Dabee, Smritee; Barnabas, Shaun L et al. (2018) Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females. Infect Immun 86:
Wood, Lianna F; Brown, Bryan P; Lennard, Katie et al. (2018) Feeding-Related Gut Microbial Composition Associates With Peripheral T-Cell Activation and Mucosal Gene Expression in African Infants. Clin Infect Dis 67:1237-1246
Balle, Christina; Lennard, Katie; Dabee, Smritee et al. (2018) Endocervical and vaginal microbiota in South African adolescents with asymptomatic Chlamydia trachomatis infection. Sci Rep 8:11109
Wood, Lianna Frances; Wood, Matthew P; Fisher, Bridget S et al. (2017) T Cell Activation in South African HIV-Exposed Infants Correlates with Ochratoxin A Exposure. Front Immunol 8:1857
Passmore, Jo-Ann S; Jaspan, Heather B; Masson, Lindi (2016) Genital inflammation, immune activation and risk of sexual HIV acquisition. Curr Opin HIV AIDS 11:156-62
El-Sayed, Mayyada M H; Brown, Sheniqua R; Mupparapu, KarunaSri et al. (2016) The effect of pH on the glucose response of the glucose-galactose binding protein L255C labeled with Acrylodan. Int J Biol Macromol 86:282-7
Tchakoute, Christophe Toukam; Hesseling, Anneke C; Blakney, Anna K et al. (2015) Reply to Thysen et al. J Infect Dis 212:1342-3
Blakney, Anna K; Tchakoute, Christophe Toukam; Hesseling, Anneke C et al. (2015) Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants. Vaccine 33:4782-9
Hesseling, A C; Jaspan, H B; Black, G F et al. (2015) Immunogenicity of BCG in HIV-exposed and non-exposed infants following routine birth or delayed vaccination. Int J Tuberc Lung Dis 19:454-62
Gervassi, Ana; Lejarcegui, Nicholas; Dross, Sandra et al. (2014) Myeloid derived suppressor cells are present at high frequency in neonates and suppress in vitro T cell responses. PLoS One 9:e107816

Showing the most recent 10 out of 13 publications