Alcohol use disorders frequently coexist with human immunodeficiency (HIV) infection. Both chronic alcohol consumption and HIV infection produce marked alterations in metabolic regulation that lead to muscle wasting, loss of bone mineral mass, and lipodystrophy. Highly active antiretroviral therapy (HAART) causes metabolic toxicity that may significantly increase comorbidity in this patient population. We have demonstrated that chronic alcohol consumption results in decreased total caloric intake, altered nutrient selection, and decreased nitrogen intake, which together led to a greater decrease in lean body mass and increased the incidence of AIDS wasting in a non-human primate model of simian immunodeficiency virus (SIV) infection. Moreover, a strong association between development of simian acquired immunodeficiency syndrome (SAIDS) wasting and decreased time to end-stage was observed. We hypothesize that chronic alcohol prevents the neuroendocrine anabolic response to feeding in SIV-infected macaques and that chronic alcohol consumption favors tissue proinflammatory and pro-oxidative milieus that disrupt the balance between the synthetic and catabolic mechanisms leading to erosion of muscle, bone, and adipose tissue mass. We predict that chronic alcohol consumption during SIV infection will result in decreased functional metabolic mass and thereby augment ART-induced metabolic burden and toxicity.
The specific aims of this proposal are: to quantify the combined impact of chronic alcohol feeding, SIV infection, and ART on skeletal muscle, bone, and adipose tissue mass and functional metabolic phenotype;to elucidate the co-morbid effects of chronic alcohol administration, SIV infection and ART on the neuroendocrine and skeletal muscle anabolic response to controlled calorie/nutrient feeding;and to determine the tissue mechanisms by which ART and alcohol increase loss of functional metabolic tissue mass in SIV-infected macaques. Results from these studies will provide critical information about the mechanisms by which alcohol, SIV, and ART cause loss of fat and lean body mass by interfering with normal neuroendocrine, cellular catabolic and anabolic processes. The proposed studies will investigate whole body, tissue, cellular, and molecular mechanisms that are altered by alcohol and disrupted by ART, accentuating metabolic toxicity.

Public Health Relevance

HIV infedion is now a chronic disease that frequently coexists with other conditions, including alcohol abuse disorders. The chronic alcohol consumption may aggravate not only the course of the infection, but may exacerbate the toxicity resulting from antiretroviral therapy. No previous studies have investigated the mechanisms affected by chronic alcohol consumption that may lead to greater toxicity when patients are treated with antiretrovirals.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Louisiana State Univ Hsc New Orleans
New Orleans
United States
Zip Code
Kaplan, Kathryn C; Hormes, Julia M; Wallace, Maeve et al. (2016) Racial Discrimination and HIV-related Risk Behaviors in Southeast Louisiana. Am J Health Behav 40:132-43
Molina, Patricia E (2016) Mechanisms Involved in Disruption of Adipose Tissue Mass Resulting from Chronic Unhealthy Alcohol Consumption. Alcohol Clin Exp Res 40:2296-2298
Guizzetti, Marina; Davies, Daryl L; Egli, Mark et al. (2016) Sex and the Lab: An Alcohol-Focused Commentary on the NIH Initiative to Balance Sex in Cell and Animal Studies. Alcohol Clin Exp Res 40:1182-91
de la Rua, Nicholas M; Samuelson, Derrick R; Charles, Tysheena P et al. (2016) CD4(+) T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia. Front Immunol 7:178
Bruce-Keller, Annadora J; Salbaum, J Michael; Luo, Meng et al. (2016) Reply to: High-Fat Diet-Induced Dysbiosis as a Cause of Neuroinflammation. Biol Psychiatry 80:e5-6
Jolley, Sarah E; Alkhafaf, Qasim; Hough, Catherine et al. (2016) Presence of an Alcohol Use Disorder is Associated with Greater Pneumonia Severity in Hospitalized HIV-Infected Patients. Lung 194:755-62
Simon, Liz; Song, Keijing; Vande Stouwe, Curtis et al. (2016) Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques. J Neuroimmune Pharmacol 11:192-213
Fleckman, Julia M; Drury, Stacy S; Taylor, Catherine A et al. (2016) Role of Direct and Indirect Violence Exposure on Externalizing Behavior in Children. J Urban Health 93:479-92
Goldsmith, Felicia; Guice, Justin; Page, Ryan et al. (2016) Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat. Mol Nutr Food Res :
Robichaux, Spencer; Lacour, Nedra; Bagby, Gregory J et al. (2016) Validation of RPS13 as a reference gene for absolute quantification of SIV RNA in tissue of rhesus macaques. J Virol Methods 236:245-51

Showing the most recent 10 out of 84 publications