Morbidity and mortality associated with HIV infection have declined in developed countries as a result of effective antiretroviral combination therapies that include protease inhibitors. However, the inability of protease inhibitors to effectively cross the blood-brain barrier and penetrate the brain parenchyma has raised concerns that although infected individuals may live longer, they may face a consequent increased risk of developing HIV-associated dementia. This speculation is based on the assumption that initial entry of HIV into the brain, which usually occurs early in infection (1), establishes lifelong persistence of the virus. Hence, although therapy effectively controls HIV replication elsewhere in the body, replication could continue in the brain unabated, ultimately initiating neurological disease.