Table 1.

Summary of potential adjuvant therapy approaches for HIV pediatric encephalopathy.

Approach	Mechanism	Findings	Ref.
ABC inhibitors	Prevent/reduce highly active antiretroviral therapy efflux	Antiretrovirals serve as substrates; can be actively pumped out of brain microvasculature	[51]
GSK-3β	Rebalance neuronal metabolism	Inhibition of GSK-3β decreased morphologic changes associated with neurodegeneration	[55, 60]
MMPs	Can cause excessive neuronal extracellular matrix degradation	Tissue inhibitors of metalloproteinase can inhibit MMPs; some antiretrovirals can decrease MMP expression	[71, 72]
Metallothioneins	Free radical scavengers	Established roles in some neurodegenerative diseases and following neuronal injury; not yet assessed in models of HIV encephalopathy	[73, 74]
Minocycline	Tetracycline analog antibiotic	Can inhibit HIV replication; reduces severity of encephalitis in SIV	[64]

ABC: ATP-binding cassette; GSK: Glycogen synthase kinase; MMP: Matrix metalloproteinase.