Alcohol and calorie-dense diets modulate immune phenotype and metabolic health in simian immunodeficiency virus infection

Alcohol misuse and calorie dense diets, especially those rich in sugar and fat, independently increase comorbidity risk among people with HIV. The objective of this study was to define the combined effects of chronic binge alcohol administration and consumption of a High Fat High Sucrose Diet (HFSD) on systemic metabolic, immunologic, and body composition outcomes under controlled conditions in an established non-human primate (NHP) model of HIV infection. Male NHPs fed HFSD diet were administered alcohol or vehicle. A subset of animals in the VEH and alcohol groups were infected with simian immunodeficiency virus and treated with antiretroviral therapy (ART). ART treatment decreased viral loads that did not differ between the vehicle and alcohol-administered NHP. There was a main effect of alcohol to significantly reduce peripheral CD4+ T cell counts and the CD4+/CD8+ T-cell ratio. Overall body composition was not significantly different between the treatment groups. However, bone mineral density was significantly lower in alcohol/SIV+ group. Alcohol decreased acute insulin response to glucose. ART effectively suppressed viral loads in vehicle and alcohol/SIV NHP. Alcohol produced significant immunologic alterations, impaired glucose insulin dynamics, and decreased bone mineral density. These findings highlight alcohol misuse as a modifiable driver of metabolic and immunologic dysfunction. Our ongoing studies will dissect the tissue specific effects of alcohol and calorie dense diets that contribute to the systemic changes.