Pathophysiological Consequences of At-Risk Alcohol Use; Implications for Comorbidity Risk in Persons Living With...

At-risk alcohol use is a significant risk factor associated with multisystemic pathophysiological effects leading to multiorgan injury and contributing to 5.3% of all deaths worldwide. The alcohol-mediated cellular and molecular alterations are particularly salient in vulnerable populations, such as people living with HIV (PLWH), diminishing their physiological reserve, and accelerating the aging process. This review presents salient alcohol-associated mechanisms involved in exacerbation of cardiometabolic and neuropathological comorbidities and their implications in the context of HIV disease. The review integrates consideration of environmental factors, such as consumption of a Western diet and its interactions with alcohol-induced metabolic and neurocognitive dyshomeostasis. Major alcohol-mediated mechanisms that contribute to cardiometabolic comorbidity include impaired substrate utilization and storage, endothelial dysfunction, dysregulation of the renin-angiotensin-aldosterone system, and hypertension. Neuroinflammation and loss of neurotrophic support in vulnerable brain regions significantly contribute to alcohol-associated development of neurological deficits and alcohol use disorder risk. Collectively, evidence suggests that at-risk alcohol use exacerbates cardiometabolic and neurocognitive pathologies and accelerates biological aging leading to the development of geriatric comorbidities manifested as frailty in PLWH.