Vascular cognitive impairment and HIV-associated neurocognitive disorder: a new paradigm

In this review, we propose that vascular cognitive impairment (VCI), with relevance for the global HIV population, is fundamentally and clinically linked to the persistence of mild forms of HIV-associated neurocognitive disorders (HAND) in ageing people living with HIV infection (PLWH). After placing our review within the context of the general literature on HIV and ageing, we review non-VCI risks for dementia in ageing PLWH. We then present the recently updated VCI nomenclature and show that the neuropsychological and neuroimaging phenotypes of VCI and HAND are largely overlapping, suggesting that further research is needed to accurately distinguish them. We further link VCI and HAND at the mechanistic level by advancing the innovative proposal that the neuro-vascular unit (NVU) may represent the primary target of HIV-related brain injury in treated HIV infection. To this, we add the fundamental impact of mild and major VCI on the NVU. Importantly, we show that the potential contribution of vascular damage to overall brain damage in ageing PLWH is probably much higher than currently estimated because of methodological limitations, and because this research is only emerging. Finally, because all VCI risk factors are more prevalent, premature, and sometimes accelerated in the HIV population at large, we conclude that the probable total burden of VCI in the global HIV population is higher than in the general population and would need to be compared to chronic conditions such as type I diabetes and multiple sclerosis to account for the disease chronicity and lifelong treatment effects. Therefore, this review is also a call to action. Indeed, it is fully established that this amount of VCI burden is a major risk factor for dementia at aged 60+.