HIV drug leaves key part of immune system vulnerable

November 27, 2000

COLUMBUS, Ohio - A drug that helps to slow the progression of HIV - the virus that causes AIDS - does not seem to prevent virus-related damage to an organ critical to the development of the immune system.

This organ, called the thymus, is especially important early in life when the human immune system is developing.

Infants who contract the virus from their mothers are particularly prone to developing immune system problems because of the damage HIV ultimately causes to the thymus.

Pregnant mothers who are HIV-positive are often given AZT, a drug that helps prevent the fetus from contracting the virus. In children and adults with HIV, AZT helps control and even reduces the proliferation of the virus in the blood.

Researchers at Ohio State University tested the effect of the drug AZT on the thymuses of young cats infected with FIV -- a virus which behaves similar to HIV and one that causes an AIDS-like disease in cats. They found that although AZT helped control and even reduce the amount of FIV in the blood and in the thymus, the virus still was able to cause significant physical damage to the thymus.

"This lack of protection surprised us," said Larry Mathes, a study co-author and a professor of veterinary biosciences at Ohio State. "It suggests that antiviral therapy in infants may need to be combined with other treatments - such as other drugs - in order to restore thymic function."

The study appears in a recent issue of the journal Antimicrobial Agents and Chemotherapy.

The researchers already knew that AZT reduces the levels of FIV and HIV in blood outside of the thymus. (AZT is also called zidovudine (ZDV) or Retrovir.) Cats were placed into one of four groups: in the first, cats were infected with FIV and treated with AZT. In a second, the animals were infected with FIV and treated with placebo. The third contained uninfected, AZT-treated cats and in the fourth, the cats remained uninfected and received only a placebo instead of AZT.

The cats received daily doses of AZT for 12 weeks. Treatment began two days before the cats were infected with the virus, so researchers could compare the levels of certain immune system cells - T cells - in the infected and uninfected groups. The virus attacks and kills T cells, which mature in the thymus.

Levels of virus present in the blood samples were determined at four, eight and 12 weeks after the initial infection. The experiments ended after 12 weeks and the researchers examined the animal's thymus glands for signs of infection.

Animals receiving the AZT treatment showed significantly reduced (by 75 to 85 percent) levels of virus in the blood and also in the thymus (by about 74 percent) when compared to animals which were infected but not treated. Yet the FIV had ultimately caused similar physical damage and inflammation to the thymuses of the cats in both of the infected groups.

Inflammation is a typical immune response to a virus or an injury - it's part of the healing process. The immune system tried to get rid of the virus in the thymus, so it launched an attack, which caused the inflammation. But reducing the virus level didn't cause the inflammation to subside. "We're not sure why it didn't," Mathes said.

"It would make sense that a decrease in virus levels would mean that the inflammation would subside and that the thymus would improve," he said. "Since that didn't happen, we assumed that it was the immune response that ended up damaging the thymus.

"Our long-term goal is to develop a therapeutic strategy to protect the thymus," Mathes said. "We want to find how we can protect it."

The research was supported by grants from the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. The study was co-authored by Kathleen Hayes, of the department of veterinary biosciences at Ohio State, and former Ohio State graduate research assistants Andrew Phipps, currently at Battelle Memorial Institute, and Sabine Francke, currently at Novartis Pharmaceuticals.
-end-
Contact: Larry Mathes, Mathes.2@osu.edu, 614-292-7317;
Written by Holly Wagner, Wagner.235@osu.edu, 614-292-8310;

Ohio State University

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