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Edward Janoff, a professor of medicine, is one of several University doctors and researchers looking for new and better ways to reduce the spread of AIDS.

Cause for hope: U researchers look for new ways to fight AIDS

U researchers look for new ways to fight AIDS

By Mary Hoff

It used to be that acquired immunodeficiency syndrome--AIDS--was a rare, isolated disease. But not any more. Since we first became aware of the existence of human immunodeficiency virus (HIV), the agent that causes AIDS, in the 1980s, the deadly pathogen has spread to every corner of the earth. By the end of 2002 the virus, which lives in (and unchecked, destroys) the immune system, had killed more than 20 million people. Today, 14,000 to 16,000 people are infected daily. "This is without a doubt the number one health problem in the world," says Phillip Peterson, professor of medicine and director of the University of Minnesota Medical School's Division of Infectious Diseases and International Medicine. "There's never been an [infectious disease] epidemic the magnitude of this epidemic." Gaining the upper hand over this deadly disease is a major focus for a number of University of Minnesota Medical School researchers. Testing treatments The sign near a door in the Academic Health Center says, very simply, ACTU. To those who have entered it over the past 16 years, those four letters spell hope. Since it opened in 1987, the University of Minnesota AIDS Clinical Trials Unit-one of only 32 of its kind in the country--has provided access to clinical drug trials to 1,900 people with HIV. "We've come from one FDA-approved drug to 19 and increased survival dramatically," says ACTU head Henry Balfour, professor of laboratory medicine and pathology. AZT, the first drug to be approved for use against HIV, became widely available in 1987. The drug was effective at prolonging lives of people with HIV but caused adverse side effects, such as nausea and anemia. It was also expensive, and HIV rapidly evolved strains resistant to its effects. Slow the spread In AIDS, as in other infectious diseases, the best medicine of all is prevention. Edward Janoff, a professor of medicine at the University and director of the Mucosal and Vaccine Research Center, is working on heading off HIV infection at the mucous membranes-where the virus first breaches the protective barrier between one person's body and another's. He is studying the transmission of HIV from mothers to infants through breastfeeding in the African countries of Burkina Faso and Uganda. Although this transmission is uncommon in the United States and Europe, where infant formula is widely available as a substitute for breast milk, it is widespread in developing countries where formula feeding is often not a viable option. About one infant becomes infected with HIV each minute in those countries, and a third of these infections occur by breastfeeding. To gain information on what types of barriers might be effective at the level of the mucous membranes, Janoff is comparing the breast milk of mothers who transmitted AIDS to their babies with that of women who did not, to see what factors might be making the difference. He hopes the information he gathers will lead to the development of a mechanism for stimulating the production of a virus-blocking substance. "In addition to medications given at the time of birth, vaccines for mothers and children may provide substantial protection to the infants," he says. His findings would also provide insight into ways to prevent HIV in mucous membranes such as those in the reproductive and intestinal tracts. Scar tactics One of the mysteries surrounding HIV has been the inability of some individuals' immune systems to rebound after being treated with drugs that dramatically reduce the virus's attack on CD4 cells, the body's main orchestrator of defenses against invaders. Last year Timothy Schacker, associate professor of medicine, and Ashley Haase, Regents' Professor of microbiology, discovered why. In addition to invading CD4 cells, HIV also harms lymphatic tissue that serves as the life support system for cells. When HIV enters the body, Haase says, the result is ravaged tissue, crippled and scarred by the invasion to the point where it can't produce what's needed to defend the body against other invaders. "Most treatment strategies for HIV/AIDS focus on stopping the virus from replicating itself in the body, which is essential to begin the process of healing and repairing of the immune system," Schacker says. "But it does not happen for everyone, and we believe this may be due to the structural damage." If, as this study suggests, permanent damage has been done, additional strategies will be needed to help the body regain its invader-fighting capabilities. Schacker and Haase are working to apply the discovery to improving diagnosis and treatment. One possible application they're studying is to use lymph node biopsies to determine how advanced the disease is, and therefore, when to intervene with therapy. ACTU head Henry Balfour sums up the U's fight against AIDS, "It's going to take time [to reduce the impact of AIDS and slow its spread], but I think we're going to get there." To learn more about HIV and AIDS research at the U, visit the Medical School's Division of Infectious Diseases and International Medicine. For information about HIV testing at the U's Boynton Health Center, see http://www.bhs.umn.edu/services/hiv.htm

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