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.
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.
|Samuelson, Derrick R; Burnham, Ellen L; Maffei, Vincent J et al. (2018) The respiratory tract microbial biogeography in alcohol use disorder. Am J Physiol Lung Cell Mol Physiol 314:L107-L117|
|Glick, Jennifer L; Theall, Katherine P; Andrinopoulos, Katherine M et al. (2018) The Role of Discrimination in Care Postponement Among Trans-Feminine Individuals in the U.S. National Transgender Discrimination Survey. LGBT Health 5:171-179|
|Molina, Patricia E; Nelson, Steve (2018) Binge Drinking's Effects on the Body. Alcohol Res 39:99-109|
|Molina, Patricia E; Simon, Liz; Amedee, Angela M et al. (2018) Impact of Alcohol on HIV Disease Pathogenesis, Comorbidities and Aging: Integrating Preclinical and Clinical Findings. Alcohol Alcohol 53:439-447|
|Ford Jr, Stephen M; Simon Peter, Liz; Berner, Paul et al. (2018) Differential contribution of chronic binge alcohol and antiretroviral therapy to metabolic dysregulation in SIV-infected male macaques. Am J Physiol Endocrinol Metab :|
|Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela et al. (2018) Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 66:35-43|
|Glick, Jennifer L; Andrinopoulos, Katherine M; Theall, Katherine P et al. (2018) ""Tiptoeing Around the System"": Alternative Healthcare Navigation Among Gender Minorities in New Orleans. Transgend Health 3:118-126|
|Glick, Jennifer L; Theall, Katherine; Andrinopoulos, Katherine et al. (2018) For data's sake: dilemmas in the measurement of gender minorities. Cult Health Sex :1-16|
|Theall, Katherine P; Felker-Kantor, Erica; Wallace, Maeve et al. (2018) Considering high alcohol and violence neighborhood context using daily diaries and GPS: A pilot study among people living with HIV. Drug Alcohol Depend 187:236-241|
|Simon, Liz; Siggins, Robert; Winsauer, Peter et al. (2018) Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration. AIDS Res Hum Retroviruses 34:178-184|
Showing the most recent 10 out of 114 publications