San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Monday, February 24, 1997 - Page A2
David Perlman, Chronicle Science Editor

The life-prolonging molecule is a common amino acid called glutathione, and it plays an essential role in cell division, in fighting infection and in preventing damage to the body from oxidation and toxic waste products.

In an experiment involving more than 200 volunteers infected by HIV, the virus that causes AIDS, the scientists found that 80 percent of those who maintained normal levels of glutathione survived during the three-year study even though their immune systems were so dangerously depleted that their lives were in danger.

By contrast, most volunteers whose glutathione levels were abnormally low died before the three years were up, even when their immune system cells were much less badly damaged.

The research was reported in San Francisco on Saturday by Leonore and Leonard Herzenberg, a husband-and-wife team of Stanford geneticists, during a meeting of the American Association of Immunologists at Moscone Center.

The Herzenbergs also described a small-scale study showing that a widely available compound known as NAC, which is chemically related to glutathione, successfully increased the supply of that vital amino acid in HIV-infected people. It also appeared to strengthen the activity of immune system cells and improved the patients' survival chances during a two- to three-year period, the Stanford scientists said.

The compound, chemically called n-acetylcisteine, is used in various forms in Europe to treat bronchitis and other lung ailments. In the United States, it is valuable as an antidote for dangerous overdoses of acetaminophen, the pain-relieving drug widely sold as Tylenol. The Herzenbergs began laboratory studies of NAC's effects on the AIDS virus in 1989, and now they have human evidence to support their theories.

In one part of their rigorously controlled clinical NAC study involving 204 volunteers, the Herzenbergs found that among those with the most severely damaged immune systems and the lowest levels of glutathione, more than 70 percent who took NAC regularly survived during the study. Of those who did not take the drug, fewer than 40 percent survived.

NAC is already used by AIDS patients, according to John S. James, the San Francisco-based editor of the national publication AIDS Treatment News, but its effectiveness in AIDS has never been tested in large-scale, well- controlled trials.

"I am reasonably convinced that many HIV-infected people who take NAC are doing a lot better," Leonard Herzenberg said Saturday. Both researchers urged government health agencies that focus on AIDS research to prepare for clinical trials quickly.

A widely used indication of damage caused by the AIDS virus is the level of immune system cells called CD4 cells that remain in the bloodstream after HIV infection begins. CD4 counts of 800 or more in the blood are normal. CD4 cell counts of 200 or higher indicate that although HIV infection is spreading, drug therapy can be highly effective and probably prolong life for many years, even though no AIDS drugs can cure. But CD4 cell counts below 200 are life-threatening.

In the Herzenberg study, 99 of the 204 volunteers had CD4 counts below 200, and their survival prospects were dim. Yet those whose glutathione levels remained normal seemed to fare better than those whose levels of the amino acid dropped -- of the 28 people with normal glutathione levels, 80 percent survived during the study, the Stanford scientists said.

For the experiment, the 99 volunteers with dangerously low CD4 counts were divided into several groups, so statistics on the survival rate of those who also had abnormally low levels of glutathione are not precise. But most in that group died within three years, the Herzenbergs said.

Low glutathione levels are common among HIV-infected people, and the pain-relieving acetaminophen drugs like Tylenol -- as well as alcohol -- are known to deplete glutathione. For AIDS patients, the effect of acetaminophen on glutathione levels can be dangerous.
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