To determine if novel treatments given to HIV associated neurocognitive disorders (HAND) mice reverse cognitive deficits and inhibit mononuclear phagocyte activity in brain.

Mice are injected with HIV-infected (HAND) or uninfected (Controls) human monocyte derived macrophages (MDM). After 5 days they undergo ORT. They are then treated subcutaneously for a week with novel therapies including curcumin, which inhibits MPs, baricitinib, a JAK inhibitor, or B18R, an interferon-alpha (IFNa) inhibitor. ORT is repeated, the mice are then sacrificed and brains are extracted and dissociated for flow cytometry including measurement of the percentage of activated MPs.

As opposed to previous studies that showed cART did not prevent cognitive dysfunction in HAND mice, all 3 novel treatments reverse ORT abnormalities. B18R and baricitinib were shown to cross the blood brain barrier. B18R and baricitinib inhibit the expression of activated MPs in mouse brains. The curcumin treated HAND mice are currently being evaluated for MP inhibition, but previous studies by others have shown that curcumin inhibits MPs.

Treatments that inhibit MP activity are effective in reversing cognitive deficits in HAND mice. The data suggest that clinical trials in humans with HAND using these agents should be undertaken.