The primary route of infection for human immunodeficiency virus (HIV), in infants is from mother to child. Following the introduction of ‘Prevention of Mother To Child Transmission’ (PMTCT), programs, HIV infection rates in newborns from mother to child (vertical transmission), have been reduced from 30 percent to less than five percent. As a result, the number of ‘HIV Exposed but Uninfected’ infants (HEU) has steadily risen. In South Africa, where 30 percent of all women of childbearing age are HIV infected, 300,000 HEU births occur per year. Recently, infection and death rates among HEU infants have been determined to be much higher than those in HIV unexposed (UE) infants. Consequently, there is an urgent need to understand why HEU infants are so vulnerable to infections. Briefly, when a person is exposed to an infecting microbe, two major arms of the immune system respond: innate immunity, which keeps the microbe at bay, and adaptive immunity, which eventually clears the infection. While it is now known that alterations in the adaptive immune system of HEU infants do take place, there is little known about how the innate immune system of HEU compared to that of the UE infant. Mr. Brian Reikie, working in collaboration with Stellenbosch University, South Africa, is conducting a pilot study to determine whether exposure to HIV, in the womb or around birth, activates the innate immune system, which then causes damage to the adaptive immune system. As well, he will explore the HIV-innate-adaptive interaction to help explain why HEU infants are so susceptible to infections. Beyond the study of HEU, this will be the first demonstration of how innate immune responsiveness correlates with development of either normal or altered adaptive vaccine immune responses over time. The findings from this project will provide the essential groundwork for urgently needed guidelines for appropriate treatment and clinical follow-up of this vulnerable population.