Infant immune activation, HIV susceptibility and ochratoxin A exposure in Khayelitsha, South Africa (P6159)

Abstract

Abstract In Khayelitsha, South Africa, 25% of new mothers are HIV-infected, and despite HIV acquisition through breast milk, WHO guidelines recommend breastfeeding to reduce infant mortality. One unexplained observation is that mixed fed infants (breast milk with formula/cereals) have up to an 11 fold increased risk of HIV acquisition. We hypothesized that this increase in HIV susceptibility is due to higher immune activation in response to non-breast milk foods. In fact, using non-invasive oral mucosa sampling, we observed increased CD4+ cells in mixed fed infants by flow cytometry. One immunomodulatory factor that may induce this immune activation in mixed fed infants is the common food contaminant Ochratoxin A (OTA). We measured OTA levels in plasma samples from infants in Khayelitsha, and found that at 2 weeks of age all infants had low OTA levels. However, at 6 weeks of age, OTA levels increased by 2 fold only in non-breastfed infants. Additionally, OTA plasma levels positively correlated with plasma levels of CXCL10 and TNF-alpha and negatively with IFN-alpha. Together, these data show that: 1. mixed fed infants have increased mucosal HIV target cells, 2. infant foods in Khayelitsha are contaminated with OTA, and 3. OTA exposure correlates with increased inflammatory and decreased antiviral activity in infant plasma. These findings suggest a mechanism for increased HIV susceptibility in mixed-fed infants and a role for food contaminants in infant HIV susceptibility.