Infants and children infected with human immunodeficiency virus-type 1 (HIV-1) are at increased risk for developing central nervous system (CNS) disease characterized by cognitive, language, motor, and behavioral impairments. The severity of HIV-related CNS manifestations in children range on a continuum from subtle impairments in selective domains to severe deterioration of global developmental skills.
HIV-related CNS dysfunction in children is primarily the result of HIV-1 infection in the brain [1, 2]. HIV-1 has been isolated from the CNS tissue of fetuses [3] and the cerebral spinal fluid (CSF) of adults soon after infection [4, 5] suggesting early CNS invasion. The timing of CNS infection for infants is variable and likely influences neuropathology and neurodevelopmental effects [3, 6–8]. Astrocytes, macrophages, and microglia may be infected with HIV-1, while neurons seem to remain largely uninfected. Various neurotoxic factors released by the virus and host cells are postulated as the main cause of neurologic damage [2, 9]. Secondary CNS complications due to immune deficiency, such as brain tumors, other infections, or cerebrovascular diseases, also may cause CNS manifestations but are less common and usually occur in older children [10].
Early in the epidemic, approximately 50–90% of children with HIV-1 infection exhibited severe CNS manifestations [11, 12] termed HIV encephalopathy. More recent studies, however, report that the prevalence of encephalopathy in HIV-infected children is approximately 13–23% [13–16].