Neurologic abnormalities are common in HIV-1 infected patients and may represent the dominant clinical manifestation of pediatric AIDS (1). Although neurological dysfunction has been directly related to CNS invasion by HIV-1 (2)(3), the pathogenesis of neurologic disorders remains unclear. Microglia, macrophages and astrocytes are major HIV-1 targets in the brain, whereas HIV-1 infected neurons have been rarely observed (4)(5)(6). This suggests that indirect mechanisms may account for the severe neuronal damage observed in these patients. Nevertheless, immature neuronal and glial cells, which are present during fetal development and early post natal life (7), may have different capabilities to support HIV-1 infection and replication compared to their mature counterparts. In addition, several neural trophic factors that exert critical roles in controlling neural differentiation, survival and function during embryonic development and early post-natal life (8) may play a part in regulating HIV-1 gene expression and virus replication in the developing brain. On the other hand, inflammatory cytokines and bioactive substances produced by HIV-1 infected and/or functionally activated accessory cells may concur in both regulating HIV-1 gene expression and replication (9) and directly altering neural cell survival, differentiation and function (7)(8) in the developing CNS, suggesting that HIV-1 infection during organ development may present unique features.
