Table 4.

Mechanisms of HIV neuropathology.

Demonstrated mechanisms
Confounding factors	HIV-related factors
Psycho-social conditions –mood disorders –psychoactive drug abuse –lack of education	CNS cell infection (macrophages, microglia, ± astrocytes)
Antiviral drugs toxicity	BBB disruption and loss of pericytes
Aging	Neurotoxicity of HIV proteins (gp120, Nef)
Cerebrovascular disease	Neurotoxicity of resident macrophages/microglia via cytokine release (TNFα)
Nutritional and liver deficiencies	Infiltrating T-cells (exacerbated during IRIS)
	Co-infections (CMV, JCV) and IRIS

Hypothetic mechanisms
HIV-triggered autoimmune reaction? Local CNS lesions related to meningeal/perivascular tertiary lymphoid organs? Autoantibody neurotoxicity? Autoimmune T-cell reaction? Triggering of non-disease-specific neurodegenerative mechanisms?