Breast milk HIV-1 RNA levels and female sex are associated with HIV-1-specific CD8 + T-cell responses in HIV-1-exposed, uninfected infants in Kenya

Abstract

Background.Although evidence supports a relationship between human immunodeficiency virus (HIV)-1 exposure and HIV-1-specific CD8 + T cell responses, studies have not demonstrated a direct association between the quantity of HIV-1 to which a person is exposed and the presence or absence of a response.Methods.From 1999 to 2005, maternal HIV-1 RNA levels were measured in blood, cervical secretions, and breast milk at delivery and 1 month after delivery. HIV-1-specific interferon (IFN)-γ Elispot assays were conducted to determine infant CD8 + T-cell responses at 3 months of age.Results.Among 161 infants tested with Elispot assays, 23 (14%) had positive results. Mothers whose infants had a positive assay had higher breast milk HIV-1 RNA levels at month 1 compared with mothers whose infants had negative Elispot assays (3.1 vs 2.5 log10 copies/mL; P =. 017). Female infants were also more likely to have positive Elispot assays than male infants (P =. 046), and in multivariate analyses, both female sex and high breast milk HIV-1 levels remained important predictors of a positive response (P =. 022 and P =. 015, respectively).Conclusions.Exposure to breast milk HIV-1 and sex were associated with development of HIV-1-specific CD8 + T-cell responses in infants. These data support a role for mucosal exposure via the oral route in induction of systemic HIV-1-specific cellular immunity. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.