Figure 1.

Proposed mechanism for human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND). HIV-1, through infected monocytes, can cross the blood brain barrier (BBB) by the Trojan horse mechanism. In the central nervous system (CNS), neuroinflammation triggered directly by viral replication or by HIV-viral proteins (glycoprotein 120 (gp120), transactivator of transcription (Tat), viral protein R (Vpr), negative regulatory factor (Nef)…) exert neurotoxic effects. They impact neurons integrity and lead to Alzheimer’s disease (AD)-like characteristics such as A generation, abnormal Tau phosphorylation, oxidative stress and excitotoxicity. The virus can induces neuroinflammation by several mechanisms: direct infection of astrocytes, BBB impairment and peripheral macrophages invasion, or massive gliosis and cytokines release. Finally, HIV⁺ patients present high glucocorticoids (cortisol) levels, characteristic of a hypothalamic–pituitary–adrenal (HPA) axis deregulation. Glucocorticoids and their receptors are highly involved in the etiology of AD. By these numerous pathways, HIV-1 induces synaptic deficits and neurodegeneration, thus leads to cognitive and behavioral deficits, and could explain the establishment of HAND in HIV⁺ patients and potentially the onset of AD.