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Alcohol abuse among people with the human immunodeficiency virus (HIV) is significant; one study found that 41 percent of HIV-infected patients met the criteria for alcoholism. Although alcohol abuse and HIV infection individually compromise immune function, the consequences of both conditions together is poorly understood. A study in the March issue of Alcoholism: Clinical & Experimental Research used simian immunodeficiency virus (SIV) infection of rhesus monkeys to examine the combined effects of chronic, binge alcohol consumption on the primary stage of SIV/HIV infection. Researchers found that alcohol consumption may increase host susceptibility to SIV/HIV infection.
"The prevalence of alcohol abuse among HIV-infected people is at least twice that found in the general population in the United States," said Gregory J. Bagby, Kai and Earl Rozas professor of physiology at Louisiana State University Health Sciences Center and first author of the study. "Several studies indicate that individuals who abuse alcohol engage in risky behaviors such as unprotected sex with multiple partners. By itself this behavior would increase the chances of becoming infected with HIV. What is not known is whether alcohol intoxication or chronic alcohol consumption alters susceptibility to infection upon exposure to HIV beyond the behavioral effects of alcohol."
Twenty-two male rhesus monkeys, four to six years of age, were given either alcohol or sucrose for four days per week for three months. The alcohol doses were individualized in order to achieve plasma alcohol concentrations of 230-250 mg/100ml (roughly the human equivalent of 6 to 10 drinks) for a five-hour period. After three months, seven alcohol-treated and seven sucrose-treated monkeys were infected with SIV; four alcohol-treated and four sucrose-treated monkeys were not. Blood samples were drawn prior to alcohol/sucrose infusions, one month prior to SIV infection, and then on days 6, 13, 20, 27, 42, and 61 post-SIV infection.
"This study had two primary purposes," said Bagby. "First, we wanted to develop an animal model to study the interactive effects of alcohol on HIV disease transmission, pathogenesis, progression and anti-viral therapy. We adapted the primate model, using SIV, which infects rhesus monkeys in the same way that HIV infects humans and produces a disease that is very similar to the human disease that leads to an immunosuppressed state and AIDS. The second purpose was to examine the effects of alcohol consumption on what is called the ?primary stage' of infection. This stage is extremely difficult to study in humans because it is rare to be able to identify infected people this early."
Approximately one week after HIV infection, there was a 64-fold increase of the HIV virus in the blood of the alcohol-treated monkeys compared to the sucrose-treated monkeys. "This most likely means that either more cells are infected with virus at this early stage or that infected cells are producing more virus," said Bagby. "If more cells are infected, it means that the alcohol increased infectivity of cells or increased the number of susceptible cells."
Alcohol consumption also enhanced lymphocyte turnover (as assessed by expression of the cell cycle protein marker Ki67) in SIV-infected monkeys during the early stage of infection, which may have contributed to the observed increase of virus in the blood.
When a body becomes infected with a pathogen or virus, explained Bagby, certain cells in the immune system become activated and start dividing or proliferating. "The cell cycle marker Ki67 increases in cells that are proliferating," said Bagby, "so an increase in this protein indicates that the immune system is responding to an infection. The cells that are produced are specifically designed to eradicate the infection. Furthermore, the increase in immune-cell production during a viral infection is accompanied by an increase in the number of cells that die. ?Lymphocyte turnover' refers to this increase in the numbers of cells that are produced and subsequently die."
"The well-documented immune-weakening effects of both alcohol and HIV infection underscore the importance of understanding the potential interactions between these two common immune suppressive factors," said Shirish Barve, associate professor in the department of medicine at the University of Louisville Medical Center. "The present work by Bagby and [colleagues] has established the much-needed animal model that could be effectively used in the study of HIV disease. Due to its similarity to HIV infection, [this] model [could] be extremely important in addressing and understanding the clinically relevant issues concerning the susceptibility of alcoholics to acquiring HIV infection and the effect of alcohol on the rate of HIV-disease progression in alcoholics."
Bagby and his co-authors intend to continue studying the effects of alcohol on HIV disease transmission, pathogenesis, progression, and therapy. "Our next study will examine the longitudinal effects of alcohol on SIV disease progression," said Bagby. "We will look at the effects of alcohol and SIV infection on disease progression, muscle wasting and behavioral deficits."
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