There is a high rate of alcohol use among HIV-infected individuals, and chronic alcohol use has been associated with high-risk sexual behavior, and reduced efficacy and adherence to antiretroviral therapy (ART). Collectively, these factors contribute to the transmission of HIV. In previous studies using the alcohol-fed rhesus macaques infected with Simian Immunodeficiency Virus (SIV), we have shown that chronic alcohol use is associated with higer levels of SIV in peripheral blood and more rapid disease progression. Additionally, we have shown that alcohol induced changes in the immunological profile of the gut mucosa, resulting in higher levels of SIV replication in the gut and peripheral blood, while others have identified alcohol-associated immunological changes in several tissues during acute SIV infection. These observations have led us to hypothesize that alcohol consumption will change the cellular milieu in the genital and rectal mucosa, providing an environment conducive to HIV infection, early replication, and shedding in genital secretions. Further, we hypothesize that increased early viral replication in these tissues will reduce the efficacy of ART in post-exposure prophylaxis and the longitudinal control of genital HIV shedding. These hypotheses will be addressed using the well-established SIV-rhesus macaque model for HIV disease, through the following specific aims. (1) Test the prediction that chronic alcohol consumption changes the cellular milieu and cytokine expression in the rectal mucosa of male macaques and the vaginal and cervical mucosa of female macaques. (2)Test the prediction that chronic alcohol exposure impacts the early dynamics of SIV infection and reduces the efficacy of post-exposure prophylaxis therapy. (3)Test the prediction that alcohol consumption increases SIV content in genital secretions, thereby increasing transmission risk. (4) Test the prediction that alcohol consumption reduces the ability of ART to suppress genital SIV shedding.
These studies will identify the impact alcohol consumption has on mucosal tissues susceptible to sexual transmission of HIV, and determine the efficacy of ART to reduce the risk of HIV transmission in the presence of chronic alcohol consumption. Because alcohol use is a modifiable behavior, these results will provide compelling evidence to limit alcohol consumption as a means to prevent HIV transmission.
|Choi, Sun-Mi; McAleer, Jeremy P; Trevejo-Nunez, Giraldina et al. (2014) Acute alcohol intoxication impairs methicillin-resistant Staphylococcus aureus clearance in the lung by impeding epithelial production of Reg3?. Infect Immun 82:1402-7|
|Siggins, Robert W; Molina, Patricia; Zhang, Ping et al. (2014) Dysregulation of myelopoiesis by chronic alcohol administration during early SIV infection of rhesus macaques. Alcohol Clin Exp Res 38:1993-2000|
|Brown, Armand O; Mann, Beth; Gao, Geli et al. (2014) Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS Pathog 10:e1004383|
|Dodd, Tracy; Simon, Liz; LeCapitaine, Nicole J et al. (2014) Chronic binge alcohol administration accentuates expression of pro-fibrotic and inflammatory genes in the skeletal muscle of simian immunodeficiency virus-infected macaques. Alcohol Clin Exp Res 38:2697-706|
|Loganantharaj, Nisha; Nichols, Whitney A; Bagby, Gregory J et al. (2014) The effects of chronic binge alcohol on the genital microenvironment of simian immunodeficiency virus-infected female rhesus macaques. AIDS Res Hum Retroviruses 30:783-91|
|Ghare, Smita S; Joshi-Barve, Swati; Moghe, Akshata et al. (2014) Coordinated histone H3 methylation and acetylation regulate physiologic and pathologic fas ligand gene expression in human CD4+ T cells. J Immunol 193:412-21|
|Molina, Patricia E (2014) Alcohol binging exacerbates adipose tissue inflammation following burn injury. Alcohol Clin Exp Res 38:33-5|
|Deshmukh, Hitesh S; Liu, Yuhong; Menkiti, Ogechukwu R et al. (2014) The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med 20:524-30|
|Simon, Liz; LeCapitaine, Nicole; Berner, Paul et al. (2014) Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques. Am J Physiol Regul Integr Comp Physiol 306:R837-44|
|El Hajj, Elia C; El Hajj, Milad C; Voloshenyuk, Tetyana G et al. (2014) Alcohol modulation of cardiac matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs favors collagen accumulation. Alcohol Clin Exp Res 38:448-56|
Showing the most recent 10 out of 37 publications