***Background.*** In Khayelitsha, as in many South African informal settlements, 25% of new mothers are HIV-infected, and 40% of HIV-infected infants acquire HIV through breast milk. The common practice of feeding infants both breast milk and non-breast milk foods, known as mixed-feeding, increases an infant\'s susceptibility to HIV by up to 11 fold. We hypothesized that the increase in HIV susceptibility seen in mixed-fed infants is due to an increase in immune activation at the oral mucosa, the mucosal surface first encountered by HIV in breast milk.

***Methods.*** Oral mucosa samples were collected with a cytobrush from HIV-unexposed infants (either exclusively breast fed or mixed-fed) in Khayelitsha, South Africa at 6 and 14 weeks of age. The cells obtained from these samples were analyzed by flow cytometry (exclusively breastfed N = 11, mixed-fed N = 8), following staining with an amine-reactive live/dead marker, anti-CD45 and anti-CD4 antibodies. In addition, a transcriptomic analysis was performed (exclusively breastfed N = 4, mixed-fed N = 13), utilizing Nanostring technology, with further analysis by qPCR.

***Results.*** At 6 weeks of age, no significant difference was observed in the percentage of HIV target cells (CD45 + CD4+) in the oral mucosa of mixed and exclusively breastfed infants by flow cytometry. However, at 14 weeks of age, the oral mucosa of mixed-fed infants had a significantly higher percentage of HIV target cells compared to infants that were exclusively breastfed (p = 0.01). In addition, transcript levels of a total of 50 immune factors, including IL-18, IL-7R, and multiple members of the caspase and keratin families, were modulated in the oral mucosa of mixed-fed infants. Particularly intriguing is a decrease in HLA class I expression in mixed-fed compared to exclusively breastfed infants.

***Conclusion.*** These data suggest that the increased HIV susceptibility of mixed-fed infants may be mediated by an increase in HIV-susceptible cells at the first site of viral exposure, and a decrease in expression of HLA class I proteins that may impair T cell mediated anti-viral responses at the oral mucosa. Understanding the mechanism of increased HIV susceptibility in mixed-fed infants may inform interventions to prevent HIV transmission across mucosal surfaces.

***Disclosures.*** **All authors:** No reported disclosures.

[^1]: **Session:** 97. HIV Related Inflammation, Complications and Comorbidities

[^2]: Friday, October 10, 2014: 10:30 AM
