The frequency of HIV-1-related central nervous system diseases has been reduced by new combinations of antiviral agents, in part through the reduction of both viral load in blood and continuous penetration of virus into brain. This will probably not be sufficient to abolish any neurological risk. HIV-1-related dementia also depends on the intensity of glial cell activation in the central nervous system, which induces reactivation of latent infection in these cells with possible reinfection of the periphery, and on secretion of soluble inflammatory mediators acting on nearby neurones. The fact that only a small subgroup of patients suffers from neurological diseases also suggests a genetic component, at the level either of viral receptors or of the immune response.