Cognitive impairment in people living with HIV: mechanisms, controversies, and future perspectives

Despite the dramatic decrease in HIV-associated neurocognitive impairment (NCI) in the combined antiretroviral treatment (cART) era, subtler neuropsychological complications remain prevalent. In this review, we discuss the changing pathophysiology of HIV-associated NCI, considering recent evidence of HIV neuropathogenesis, and the pivotal role of cART. Furthermore, we address the multifactorial nature of NCI in people living with HIV, including legacy and ongoing insults to the brain, as well as host-specific factors. We also summarize the ongoing debate about the refinement of diagnostic criteria, exploring the strengths and limitations of these recent approaches. Finally, we present current research in NCI management in people living with HIV and highlight the need for using both pharmacological and nonpharmacological pathways toward a holistic approach.