The natural history of human immunodeficiency virus type-1 infection in infants differs markedly from adults. In adults, plasma viral load peaks during acute infection and is subsequently reduced to a.1 log lower level set-point over the next 6�C8 weeks. This viral load set-point may be maintained for years, sometimes at levels below detection. In contrast, infants experience very high plasma viral loads and lack the characteristic decline to set-point observed in adults. Infant CD4 + T cells are rapidly depleted during the first year of life and there is much morbidity due to opportunistic infection. In the absence of antiretroviral therapy, 2-year mortality rates as high as 52% have been reported in African SE 175 cohorts. Adult studies of HIV-1 infection and SIV models have demonstrated the importance of HIV-specific CD8 + T cells in limiting viral replication. The rapid HIV-1 disease progression experienced by infants may be a consequence of suboptimal T cell responses during early life. Studies conducted in perinatally infected infants report less frequent SF-22 detection of CD8 + T cell responses, and responses of a smaller magnitude than are typically observed in HIV-infected adults. There are conflicting findings regarding the association between CD8 + T cell responses and HIV-1 viral load or disease progression in infants and children; with some studies showing a positive, negative, or absence of correlation. The detection of escape mutations suggests some infant CD8 + T cells exert sufficient selection pressure to drive viral evolution. In 85 vertically infected infants examined longitudinally during the first year of life, we observed an increase in the magnitude of HIV-specific IFN-c responses over time. We also found infants who acquired HIV-1 after 1 month of age were able to generate IFN-c responses more rapidly than infants with in utero or peripartum infection. Together these data suggest that the capacity of the infant cellular immune system to generate HIV-specific IFN-c responses increases rapidly in the first months of life. Understanding the specific mechanisms by which infant T cells fail to contain HIV-1 is important to the design of vaccines appropriate for use in infants. In addition, defects in infant immune responses that explain poor viral control may contribute more broadly to our understanding of HIV-1 immune pathogenesis.