Additional findings were that (1) Vpr induces inflammation via specific pathways, including the PI3K/AKT, p38-MAPk, JNK-SAPK and the Sur1-Trpm4 channel in astrocytes and the p38 and JNK-SAPK pathways in myeloid cells, and that (2) the Vpr protein amino acid signatures (73R, 77R and 80A) may play an important role in exacerbating neuroinflammation and the neuropathophysiology of HAND. This evidence concerns the gene TRPM4 and HIV-associated neurocognitive disorder.