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.