HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

Despite entering the era of combination antiretroviral therapy (CART), HIV-associated neurocognitive disorder (HAND) remains prevalent; however, less severe forms of HAND now predominate, and the most severe form, HIV-associated dementia, is rareIn individuals treated with CART, the risk of HAND increases with age and in the presence of cardiovascular disease risk factorsLatent HIV can persist in the brain even when systemic virological control is achieved with CART, thereby hampering efforts to eradicate HIVAnimal models of CNS HIV infection — such as macaques infected with simian immunodeficiency virus — develop severe HAND, viral encephalitis and neuronal apoptosis, and are central to understanding the immunopathogenesis of HIV-induced CNS damageA growing body of work indicates that mild HAND can be modelled in immunocompetent mice infected with chimeric HIV (a model known as EcoHIV), and in chronically HIV-infected immunodeficient mice reconstituted with human immune systemsTo date, clinical trials of HAND therapies have been unsuccessful, but further trials for the treatment of HAND are forthcoming, including a trial of intranasal insulin