Table 2 Pharmacological agents investigated for HAND treatment
From: Potential pharmacological approaches for the treatment of HIV-1 associated neurocognitive disorders
Drug class | Compound | In vitro system | In vivo system/clinical trials |
|---|---|---|---|
Natural products | Resveratrol | Rat hippocampal slices exposed to Tat [105]* | Not evaluated to date |
Curcumin | Mouse microglia cultures and rat neurons treated with gp120 V3 loop [215] | Not evaluated to date | |
Rat hippocampal slices treated with gp120 V3 loop [216,217,218]* | |||
Mouse microglia exposed to gp120 [219] | |||
Antidiabetics | Insulin | Primary human microglia cultures infected with HIV-1 [229] | FIV infected cats [229] |
Rosiglitazone | Primary cultures of mixed rat glial cells exposed to gp120 [118] | Mice injected with gp120 ICV [118] | |
MMP-9 deficient mice injected with Tat [227] | |||
15d-PGJ2 | Not evaluated to date | ||
Pioglitazone | Primary cultures of mixed rat glial cells exposed to gp120 [118] | Mice injected with gp120 ICV [118] | |
Troglitazone | Human brain endothelial cells exposed to Tat [226] | Not evaluated to date | |
Fenofibrate | Not evaluated to date | MMP-9 deficient mice injected with Tat [227] | |
Glutamate modulators | Memantine | Not evaluated to date | |
HIVE SCID mice [239] | |||
SIV infected macaques [240] | |||
NitroMemantine | Not evaluated to date | gp120 transgenic mice [243] | |
6-Diazo-5-oxo-l-norleucine | HIV infected microglia and macrophages [180] | EcoHIV infected mice [180] | |
PPARγ agonists (rosiglitazone; pioglitazone) | Primary cultures of rat astrocytes exposed to gp120 [118] | Not evaluated to date | |
Statins | Simvastatin | Not evaluated to date | Rats ICV injected with gp120 [64] |
Unspecified | Not evaluated to date | HIV+ human patients on statin therapy [19] | |
Antiretrovirals | Maraviroc | Not evaluated to date | SIV infected macaques [257] |
HIV patients on stable cART [258] | |||
IFN therapy | IFNβ | Primary human fetal microglia infected with HIV-1 [270] | Transgenic gp120 mice [271] |
Rat cerebrocortical cultures exposed to gp120 [271] | |||
B18R | Not evaluated to date | ||
Fumaric acid derivatives | Monomethyl fumarate | Primary human astrocytes co-cultured with HIV-1 transduced monocytoid cells [339] | Not evaluated to date |
DMF | HIV-1 infected human monocytes [281] | Not evaluated to date | |
Primary rat neurons exposed to HIV-1 infect human monocytes [281, 340] | |||
Human neuronal cells exposed to HIV infected human macrophages and neuroblastoma cells [285] | |||
Antibiotics | Minocycline | Not evaluated to date | SIV infected macaques [293] |
Rats injected with gp120 ICV [64] | |||
HIV+ patients [295] | |||
NSAIDs | Meloxicam | Not evaluated to date | Transgenic HIV-1 rats [298] |
Steroid alkaloids | dCA | Primary human CD4+ T-cells infected with HIV-1 [301] | Tat transgenic mice [302] |
Human astrocytic cell line transfected with Tat [302] | |||
Beta galactoside binding proteins | Galectin-1 | Primary human microglia transfected with Tat [312] | Not evaluated to date |
Cannabinoids | ACEA | Human brain microvascular endothelial cells with human astrocytes exposed to gp120 [319] | Not evaluated to date |
CP55,940 | Human brain microvascular endothelial cells with human astrocytes exposed to gp120 [319] | Not evaluated to date | |
WIN55,212-2 | Human neurons exposed to gp120 [320] | Not evaluated to date | |
Mouse prefrontal cortices exposed to Tat [321] | |||
Anandamide | Mouse prefrontal cortices exposed to Tat [321] | Not evaluated to date | |
AM1241 | Primary human and murine neural progenitor cells exposed to gp120 [322] | Transgenic gp120 mice [322] | |
Gp1a | Not evaluated to date | HIVE mice [323] | |
Others | Fluconazole and Paroxetine combination | Not evaluated to date | SIV infected macaques [331] |
HIV+ patients with HAND [332] | |||
Fluconazole | Mixed rat hippocampal cultures exposed to gp120 and Tat [331] | HIV+ patients with HAND [332] | |
Paroxetine | Mixed rat hippocampal cultures exposed to gp120 and Tat [331] | HIV+ patients with HAND [332] | |
Chloroquine | Not evaluated to date | Rats ICV injected with HIV gp120 [64] | |
HIV+ adults on ART [335] | |||
Asymptomatic HIV infected adult patients not on ART [336] |