Pediatric HIV infection remains a global health crisis with a worldwide infection rate of 2.1 million (UNAIDS, 2013). Children are much more susceptible to HIV-1 neurological impairments than adults, which is exacerbated by co-infections. A main and obvious obstacle in pediatric HIV research is sample access. The proposed studies will take advantage of ongoing pediatric SIV pathogenesis and vaccine studies to maximize the use of nonhuman primate resources by expanding on the original pediatric SIV-related immunology studies to include quantitative neuropathology studies. We hypothesize that HIV infection in infants will induce neurodegeneration and impaired neurogenesis. Neonatal rhesus macaques (Macacca mulatta) that infected with SIVmac251 will be used to test this hypothesis. After a 6 to 33 week survival time, the animals were sacrificed for quantitative histopathological analysis. AIM 1 will determine the extent of pediatric SIV-induced neurodegeneration in the hippocampus and fronto-limbic system and its relationship to viral loads. In AIM 2 we will determine the mechanism(s) of pediatric SIV-induced neuronal loss in the hippocampus and fronto-limbic system. The goal of this project is to assess the impact of early HIV infection on the brain towards the long-term goal of evaluating treatment paradigms designed to protect the integrity of the developing brain from combined viral and bacterial infections through an interdisciplinary approach.