The HIV-1 envelope variant Asn283 (N283), which occurs in the CD4 binding site within gp120, has been found at a high frequency within brain samples derived from patients with HIV-1-associated dementia [38] and demonstrated the ability to decrease the gp120-CD4 dissociation rate, allowing for the use of lower levels of CD4 for viral entry as well as increasing viral replication in macrophages and microglia. This evidence concerns the gene ITIH4 and dementia.