Sep. 25, 2006 Alcohol abuse can impair a person's immune system, leading to infections like pneumonia. Alcohol abuse is also more common among individuals already infected with human immunodeficiency virus (HIV) than among the population as a whole. New research findings show that chronic binge drinking can accelerate the progression of end-stage simian immunodeficiency virus (SIV) among rhesus macaques, likely mimicking what happens to humans infected with HIV.
Results are published in the October issue of Alcoholism: Clinical & Experimental Research.
"Previous research has found that HIV-infected people are more likely to consume alcohol than the general population," said Gregory J. Bagby, professor of physiology and medicine at Louisiana State University Health Sciences Center and corresponding author for the study. "One very recent study conducted in Miami, for example, found that more than 60 percent of its HIV-infected participants reported heavy alcohol use."
Bagby said that the protracted nature of HIV disease, along with the complex behaviors of HIV+ patients, makes the study of alcohol consumption or abuse on HIV-disease progression extremely difficult.
"While alcohol abuse is known to impair immune defenses," he said, "resulting in a higher incidence and severity of infections -- especially pneumonia -- the adverse consequences of heavy alcohol consumption on the HIV-infected patient as it relates to disease progression are poorly understood. The few studies that exist have failed to find an association between alcohol use and HIV disease progression. For this reason, we adopted the rhesus macaque SIV model of HIV disease in order to more effectively isolate the effect of alcohol consumption on infectivity, pathogenesis and progression."
"The key issue with alcohol consumption and HIV/AIDS is when to start individuals on life-saving antiretrovirals versus the need to avoid their toxic effects that damage the liver and gut along with the alcohol," added Kendall Bryant, coordinator of HIV/AIDS research at the National Institute on Alcohol Abuse and Alcoholism. "This 'set point,' which is unobserved, is not characterized by traditional measures of disease status. Dr. Bagby's research suggests that the speed of progression of AIDS -- at least for alcohol users -- is in part set by past and current drinking very early on in the disease. This tells us that we need to get HIV+ alcohol users into treatment much earlier in order to reduce their alcohol use."
For 12 weeks, study authors administered alcohol to 16 male rhesus macaques for five hours on four consecutive days per week via an indwelling intragastric catheter in order to attain a blood alcohol concentration of 0.23 to 0.28 percent. This would be considered the human equivalent of "chronic binge drinking." Control rhesus macaques (n=16 males) were given a sucrose solution under the same conditions. After three months, eight alcohol-treated and eight sucrose-treated macaques were inoculated with 10,000 times the ID50 of SIVDeltaB670 and followed to end-stage disease. Eight alcohol-treated and eight sucrose-treated macaques were not infected with SIV.
"There are two key findings," said Bagby. "First, chronic binge alcohol consumption accelerated time to AIDS of rhesus macaques infected with SIV, a virus that mimics what happens to humans infected with HIV. The average time to end-stage disease was decreased from 900 days in control animals to 374 days in the alcohol-treated rhesus monkeys. Second, animals receiving alcohol had higher viral loads in the blood in the early months after being infected with the virus. This higher viral load is associated with more rapid disease progression in both SIV-infected rhesus macaques and HIV-infected humans. Because SIV infection in rhesus macaques is so similar to what happens in HIV infected humans, we can expect that alcohol would have similar consequences in humans."
"The study gives us one more piece of the puzzle about the complex effects of alcohol on the progression of HIV disease," said Bryant. "What people don't realize is how complex the life cycle of the virus is and how it interacts in a very directed way with host characteristics such as drinking. We want to lengthen the life of HIV-infected individuals so that they can live a life as anyone with a chronic disease that needs to be managed. If these findings are confirmed in HIV+ individuals, the prevention implications are that both past and current alcohol use impacts disease progression and that many additional years of life will be lost if one continues to drink while infected."
Bagby noted that although his study implicates alcohol abuse as a cofactor in accelerating SIV disease progression and, by extrapolation, HIV disease -- the exact mechanisms by which this occurs remain unclear.
"Each episode of alcohol intoxication can suppress multiple elements of immune function in humans," he said. "This suppression can be largely responsible for the increased incidence of infections such as pneumonia. However, chronic alcohol consumption can also stimulate the immune system, leading to diseases like hepatitis. In this case, perhaps both effects of alcohol are involved: immunosuppression could increase the incidence of opportunistic infections, and immune stimulation could activate cells infected with the virus, causing more cells to become infected."
Notwithstanding what mechanisms may be involved, both Bagby and Bryant said that HIV+ individuals must realize that heavy alcohol consumption can accelerate disease progression to AIDS and death.
"We also need to prioritize questions and realize that the HIV epidemic is still with us and that it is growing in many countries with few health resources," said Bryant. "Alcohol use is an important modifiable factor in the AIDS epidemic. It should not be overlooked or underfunded."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Chronic Binge Ethanol Consumption Accelerates Progression of Simian Immunodeficiency Virus Disease," were: Ping Zhang of the Department of Physiology at LSU Health Sciences Center; Jeanette E. Purcell of the Division of Laboratory Animal Medicine at Tulane National Primate Research Center; Peter J. Didier of the Division of Comparative Pathology at Tulane National Primate Research Center; and Steve Nelson of the Departments of Medicine and Physiology at LSU Health Sciences Center. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.
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