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

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 nonhuman primate (NHP) model of HIV infection. Male NHPs fed HFSD diet were administered alcohol or vehicle. A subset of animals in the vehicle (VEH) and alcohol groups was infected with simian immunodeficiency virus (SIV) and treated with antiretroviral therapy (ART). ART treatment decreased viral loads, which did not differ between the vehicle- and alcohol-administered NHPs. 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 the alcohol/SIV+ group. Alcohol decreased the acute insulin response to glucose. ART effectively suppressed viral loads in vehicle and alcohol/SIV NHPs. Alcohol produced significant immunological 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.NEW & NOTEWORTHY This study examined the interactions of a calorie-dense diet and alcohol in SIV-infected and SIV-seronegative nonhuman primates on systemic viral loads and immunological and metabolic measures. ART effectively suppressed viral loads, irrespective of alcohol administration. Alcohol produced significant immunological alterations and decreased bone mineral density in SIV infection. Alcohol impaired glucose-insulin dynamics irrespective of SIV infection, highlighting a significant metabolic maladaptation. The results highlight the interaction of diet and alcohol on increasing the risk for comorbidities in HIV.