Hence, there has been some debate whether gp120-associated neuronal injury observed in HAND is the result of indirect effects mediated by the release of neurotoxic, proinflammatory host factors from infected or activated glial cells, or rather the result of a direct neurotoxic effect of soluble HIV proteins shed from infected host cells and virus [12, 33, 34]. This evidence concerns the gene ITIH4 and HIV-associated neurocognitive disorder.