Abstract
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.
Highlights
The alcohol-mediated cellular and molecular alterations are salient in vulnerable populations, such as people living with human immunodeficiency virus (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
Though ART attenuates expression of microglial markers of neuroinflammation in the frontal cortex and monocyte/macrophage markers of neuroinflammation in the basal ganglia, it did not ameliorate the alcohol-associated inhibition of growth factor signaling in the frontal cortex of simian immunodeficiency virus (SIV)-infected macaques. These findings suggest that while ART may be effective in reducing neuroinflammation associated with infection and alcohol, it is not sufficient to attenuate the deficits in Brain-derived neurotropic factor (BDNF) signaling and may explain the persistence of HIV-associated neurocognitive disorder (HAND) despite widespread ART use (Maxi et al, 2019)
Summary
At-risk alcohol use is the seventh leading cause for morbidity and mortality accounting for 5.3% of all deaths, and the leading cause of disability-adjusted life-years (DALYs) among individuals 15–49 years of age (Burton and Sheron, 2018). Alcohol-Related Comorbidities in PLWH continues to damage the brain and other organs, and locks the individual into a motivational cycle of binge/intoxication, withdrawal, and craving/anticipation of renewed drinking during repeated abstinence (Koob, 2021). The primary driver of excessive alcohol drinking stems from a dysregulation of motivational behaviors regulated by the brain. The adaptive function of these brain regions and goal-directed behaviors can be compromised by multiple genetic and environmental factors, including the excessive use of alcohol. AUD significantly decreases life expectancy and increases the risk of mortality from mental disorders (10-fold), and from cardiovascular diseases and cancers (two-fold) (Roerecke and Rehm, 2014). The increased risk of mortality associated with atrisk alcohol use results from alcohol-induced end organ injury spanning cardiopulmonary, gastrointestinal, immune, adipose, musculoskeletal, and nervous systems
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