In patients living with HIV infection, the prevalence of insomnia and other sleep disturbance is nearly 2.5 times higher than healthy controls and affects nearly 70% of this population. The importance of sleep in healthy cognition has been well-established, and its disruption may contribute to neurocognitive deficits observed in infected individuals. Additionally, both HIV infection and sleep have established bidirectional relationships with neurodegenerative diseases of aging, which represent a rising affliction in these patients. This connection presents a novel opportunity for pharmacological intervention-- we may ameliorate HIV-associated sleep disturbances by treating the disease itself, or improve neurocognitive function in these patients by treating the sleep disruption. In order to assay the efficacy of novel therapeutics and treatment modalities, we assessed the sleep phenotype exhibited in the EcoHIV mouse model of infection. By multi-day locomotor and polysomnography recordings of electroencephalography (EEG) and electromyography (EMG), we examined the uninterrupted sleep-wake patterns of EcoHIV infected mice, and uninfected control littermates. Across the entire 24-hour period, and particularly during their daytime period of deep sleep, mice infected with EcoHIV exhibited more wakefulness and less consolidated sleep than their healthy counterparts. This effect manifested in more frequent arousals, shorter sleep bouts, and decreased slow-wave power. Additionally, the amount of rapid eye movement (REM) sleep was significantly decreased. Similarly to people with HIV infection, the EcoHIV mouse model exhibited sleep disturbances suggestive of multi-modal insomnia. These data suggest that this model carries the disease-relevant sleep phenotype, and can be used to trial possible therapeutics. We then assessed the effect of a novel glutamine antagonist prodrug, JHU083, on these phenotypes, to determine if improved sleep can slow the progression of HIV-associated neurocognitive consequences.  
 

Barbara Slusher is an inventor on the patent which covers JHU083 and similar compounds.