HIV-associated dementia is primarily caused by infected macrophages and microglial cells within the central nervous system. These cells serve as reservoirs for HIV and release neurotoxic substances, such as inflammatory cytokines and viral proteins, leading to neuronal dysfunction and death. Importantly, HIV does not directly infect neurons, but the indirect effects of infected immune cells cause the cognitive and motor deficits observed in the disease. This mechanism explains the characteristic subcortical dementia seen in HIV patients.

Reference: Harrison's Principles of Internal Medicine, Fauci et al., 20th Edition.