Defining correlates of protective immunity in HIV-1 transmission is a priority in HIV-1 vaccine research. Mother-to-child transmission of HIV-1 provides an excellent model in which to study the role of cytotoxic T lymphocyte (CTLs) because infants of HIV-1 infected mothers are repetitively exposed to HIV-1 (in utero, during delivery, and through breast milk) and initial exposure may induce CTLs that protect from subsequent exposure. In Kenya, many HIV-1 seropositive mothers choose to breast feed despite knowledge of breast milk HIV-1 transmission risk and provision of an alternative, because of stigma attached to HIV infection and risk associated with formula feeding. The effect of infant CTLs on breast milk HIV-1 transmission risk can be determined in infants of these mothers. The amount, time, and route of infant viral exposure can be measured, enabling systematic evaluation of determinants of CTL induction in this model. This observational prospective study aims to determine the effect on breast milk HIV-1 transmission of CTLs in infants of HIV-1 infected mothers in Nairobi. After informed consent, pregnant HIV-1 seropositive women will be enrolled in the study. Women in the study will be provided with short course antiretrovirals and will feed the infant according to their preference. Maternal plasma and genital specimens will be collected antenatally and at delivery, and breast milk and plasma specimens collected during the postnatal period for HIV-1 assays. Infants will be serially evaluated for HIV-1 by PCR, and infants who are uninfected at birth assessed for CTL responses at birth, and at 1, 3, and 12 months of age. CTL responses will be quantitated with ELISPOT assays using HLA-typing techniques and epitopes previously developed for Nairobi. Among breast feeding infants, the effect of CTL at birth and at 1 month on subsequent risk of breast milk transmission of HIV-1 will be evaluated in the context of other potential correlates of breast milk transmission. The prevalence and correlates of infant CTLs at birth, 1, 3, and 12 months will be determined. To determine whether ongoing breast milk exposure sustains infant CTL responses, the prevalence of CTLs at one year will be compared in breast and formula feeding uninfected infants. Demonstration of a protective effect of CTLs on breast milk transmission will be specifically relevant to prevention of breast milk transmission of HIV-1 and to HIV-1 vaccine development in general.
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