Figure 2:

Substances of abuse impact several processes of HIV neuropathogenesis leading to cognitive impairment. Methamphetamine, cocaine, and opioids contribute to HAND, in part by: A. Facilitating infected monocyte and perhaps T-cell transmigration across the BBB; B. Disrupting BBB integrity through decreased tight junction proteins, and increased metalloproteinases and adhesion molecules; C. Increasing HIV infection and replication in macrophages and microglia, contributing to increased viral load in the CNS; D. Releasing virus and/or viral proteins, and other inflammatory mediators including reactive oxygen species and cytokines; E. Impairing astrocyte metabolic processes and functioning that are essential for brain homeostasis; F. Increasing extracellular dopamine through impaired dopamine reuptake and storage mechanisms; G. Further recruiting monocytes due to increased chemokines and extracellular dopamine in the CNS. H. All of these processes (A-G) may contribute to neuronal injury, and loss, resulting in HAND.