Alcohol abuse and human immunodeficiency virus (HIV) infection are major public health problems and frequently coexist in the same individual. Although several studies have shown a significant association between alcohol consumption and the risk of being infected with HIV, it is unclear whether this association is due to behavioral and/or biomedical mechanisms. Studies of HIV-infected patients are inherently limited in their ability to control for variables such as timing and dose of HIV exposure, nutrition, concurrent use of drugs of abuse, use of anti-retroviral therapy, and the frequency of alcohol consumption and amount of alcohol consumed. In order to study the impact of alcohol on HIV infection, we developed a model of chronic alcohol consumption in rhesus macaques monkeys (Macaca mulatta) infected with simian immunodeficiency virus (SIV), a lentivirus closely related to HIV that infects and destroys CD4+ cells and produces a progressive immunodeficiency representative of HIV disease. Using this model, our studies have shown that plasma viral loads are significantly higher in alcohol-consuming macaques at 60-120 days after SIV infection (viral set point) than in control animals. The viral set point has been shown to be predictive of disease progression, and in our studies, alcohol consumption was associated with accelerated disease progression to end-stage disease. The rhesus macaque SIV model should be useful in identifying the mechanisms by which alcohol increases the viral load of HIV, affects HIV-associated comorbidities, and influences the efficacy of anti-retroviral therapy.