Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection

Background: Alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (HIV)-infected population. However, its impact on disease progression is unknown. Studies dissecting the drug-induced or alcohol-induced metabolic derangements that are likely to alter the course of disease progression are lacking. This is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (HAART). HIV infection has become a more chronic disease during which alcohol-induced metabolic alterations may become more prevalent and pronounced. Methods: The present study used a model of chronic intragastric alcohol administration initiated 3 months before intravenous simian immunodeficiency (SIV) inoculation and continued thereafter throughout the course of SIV infection, to investigate the impact of chronic alcohol binge-like consumption during the initial 10-month asymptomatic phase of SIV infection in nonhuman primate rhesus macaques. Anthropometric, metabolic, biochemical, nutritional, and immune state indicators were examined before infection and at 3-month intervals in asymptomatic chronic alcohol-treated SIV-infected macaques and time-matched isocaloric and uninfected controls. Results: Intravenous SIV Delta B670 infection resulted in increased viral load, decreased circulating CD4+/CD8+ lymphocyte ratio, and increased lymphocyte proliferation (Ki67/CD3+). Chronic alcohol/SIV+ animals showed a higher viral load at 3 months post-SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF-I, myostatin, or the ubiquitin ligase muscle atrophy F-box protein (MAFbx) did not differ from basal during the 10-month asymptomatic period of infection. However, muscle TNF-alpha mRNA expression was markedly increased at 10 months post-SIV infection in alcohol/SIV+ animals. Discussion: These findings suggest that chronic alcohol accelerates nutritional and metabolic dysregulation during SIV infection and may favor a skeletal muscle proinflammatory state, possibly conducive to subsequent muscle wasting.