Host peripheral immune dynamics increase HIV-associated neurocognitive disorders incidence and progression

Human immunodeficiency virus (HIV) infection causes rapid depletion of CD4+ T cells, and fortunately, combination antiretroviral therapy (cART) allows significant immune reconstitution. However, significant HIV-associated pathologies, including HIV-associated neurocognitive disorders (HANDs), remain prevalent even in cART era. More recent animal models of HIV pathogenesis suggest that significant gut damage and dysregulation contributes to ongoing peripheral immune activation even during cART. Several of the peripheral proinflammatory processes, including increased immune trafficking to the central nervous system (CNS), intermediate monocyte differentiation, and blood–brain barrier dysfunction, contribute to neuroinflammation and infection. This neuroinflammation is then associated with neurodegeneration, loss of synapse function, and decreased neurogenesis. This lost connectivity and volume maybe contribute to HAND symptomology.