Lentiviruses, a group of retroviruses that includes HIV-1, have been known to be neurovirulent since landmark studies by Sigurdsson and others, who showed that chronic lentiviral infections could take hold in the central nervous system (CNS; reviewed in ref. 1). Since their discovery, HIV-1 and, to a lesser extent, HIV-2 have been recognized as CNS pathogens that can cause a subcortical dementia (HIV-associated dementia; HAD) in a significant proportion of infected patients (2). In HAD, as distinct from conventional cortical dementias, memory impairment typically occurs either in association with or following other cognitive symptoms like inattention, apathy, and psychomotor slowing. Motor symptoms such as lack of coordination are also characteristic of this condition. The neuropathological changes induced by HIV-1 infection of the CNS include pallor of the myelin sheaths, proliferation or prominence of astrocytes, and the formation of multinucleated giant cells (syncytia). Microglia and brain macrophages are the main cellular targets for HIV infection in the CNS, and syncytium formation is a signature finding for this infection, since it results from interactions between the viral glycoproteins gp120 and gp41 and the principal cellular HIV-1 receptors in microglia, CD4 and CCR5. The presence of multinucleated giant cells in the CNS is the most specific finding in HIV infection, and it is roughly correlated with the antemortem diagnosis of HAD (3).