NEW YORK, March 03 (Reuters) -- Maintaining healthy levels of a peptide called glutathione may play a "pivotal" role in slowing the progression of AIDS, researchers say.
"People with HIV who have lower glutathione levels (also) have a much lower probability of surviving over the course of three years than do people with normal glutathione levels," concludes Stanford University School of Medicine geneticist Dr. Leonard Herzenberg.
Glutathione (GSH) is a molecule involved in a range of normal cell activities, including cell division and the clean-up of intracellular toxins. But a low glutathione level effectively "decreases cell survival, alters (immune system) T cell functions, and increases HIV replication" in HIV-infected cells, researchers say.
They add that GSH-level measurements may be an accurate marker of AIDS progression. Traditionally, physicians have assessed the condition of HIV-infected patients by measuring levels of CD4 cells, part of the immune-system. CD4 counts of 1,000 cells per milliliter (ml) of blood are normal in healthy, uninfected individuals. These numbers drop precipitously in those infected with HIV. CD4 levels under 200 cells/ml are thought to leave AIDS patients vulnerable to a number of life-threatening opportunistic infections.
But CD4 counts may not tell the whole story, according to the study.
Herzenberg's team divided 204 HIV-positive, (but AIDS-asymptomatic), patients into two groups. They gave one group a GSH-boosting drug called N-acetylcysteine (NAC), and the other group a placebo.
Ninety-nine of the 204 Stanford study subjects had initial CD4 counts of under 200 cells/ml. Most of the 99 who received placebo (and thus maintained low glutathione levels) died within the three-year study period.
"In contrast," said Herzenberg, "of the 28 people who started the study with low CD4 counts but maintained normal glutathione levels, 23 survived. In other words, about 80% of these people survived, even though their CD4 cell counts indicated their survival was unlikely."
Herzenberg believes "glutathione levels matter to patient survival," and the study says clinical measurements of those levels "emerges as a powerful yardstick for predicting survival in HIV infection."
And Herzenberg believes that boosting GSH levels can keep AIDS patients healthier longer. "We know that NAC will raise glutathione levels in patients. Therefore, it's logical to suggest that NAC will help HIV patients live longer," he says. NAC, a drug the study calls "inexpensive (and) nontoxic," works by supplying the amino acids crucial to the replenishment of cellular GSH.
However, other factors deplete the body's GSH. Ultraviolet radiation (usually from sunlight), drinking, and the consumption of acetaminophen-containing drugs (like Tylenol) can actually lower GSH levels, the researchers warn. Avoiding those factors would "minimize GSH deficiency in HIV-infected individuals," they say.
The study "provides the first clear indication that GSH deficiency plays a pivotal role in determining how quickly the final stages of HIV disease progress." Herzenberg says clinical trials assessing impact of NAC administration on long-term HIV patient survival is the next logical step in research on the subject.
SOURCE: Proceedings of the National Academy of Sciences (1997;94:1967-1972)
