HIV proteins bind to receptors on the cell’s surface, and also cross the plasma membrane. Resulting in aberrations in Ca+ homeostasis, activation of calpain 1, p35 cleavage to p25 that hyperactivates CDK5 resulting in aberrant phosphorylation of TAU, CRMP2 and others. The onslaught of HIV infection, neuroinflammation and HIV protein expression culminates in neurodegeneration and ultimately HAND.