Metabolic Syndrome and Cardiovascular Disease Impacts on the Pathophysiology and Phenotype of HIV-Associated Neurocognitive Disorders

Evidence from epidemiological studies on the general population suggests that midlife cardiovascular disease (CVD) and/or metabolic syndrome (MetS) are associated with an increased risk of cognitive impairment and dementia later in life. In the modern combined antiretroviral therapy (cART) era, as in the general population, CVD and MetS were strongly and independently associated with poorer cognitive performances of sustained immunovirologically controlled persons living with human immunodeficiency viruses (PLHIVs). Those findings suggest that CV/metabolic comorbidities could be implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND) and might be more important than factors related to HIV infection or its treatment, markers of immunocompetence, or virus replication. The association between CVD/MetS and cognition decline is driven by still not well-understood mechanisms, but risk might well be the consequence of increased brain inflammation and vascular changes, notably cerebral small-vessel disease. In this review, we highlight the correspondences observed between the findings concerning CVD and MetS in the general population and virus-suppressed cART-treated PLHIVs to evaluate the real brain-aging processes. Indeed, incomplete HIV control mainly reflects HIV-induced brain damage described during the first decades of the pandemic. Given the growing support that CVD and MetS are associated with HAND, it is crucial to improve early detection and assure appropriate management of these conditions.