The Wall Street Journal - Thursday, 31 October 1996.
Michael Waldholz, Staff Reporter of The Wall Street Journal

Earlier this year scientists showed that a "cocktail" of drugs including new so-called protease inhibitors had produced startling results in reducing the presence of the AIDS virus in many patients. But AIDS researchers lacked a second crucial attack-- a way to also boost levels of the immune system's T-cells to further beat back the retreating virus and other life-threatening infections. Now a government research team says it may have found a way to do this, too.

The new drug is a genetically engineered version of interleukin-2, or IL-2, a human protein that has been studied against AIDS and cancer since 1983. For years AIDS scientists have viewed IL-2 as promising because the protein's main job is to spur the growth of the white blood cells called T-cells, the immune-system defenders that are targeted and destroyed by HIV, the virus that causes AIDS.

Now, research surfacing in recent weeks shows that the man-made protein, when used alongside the protease "cocktails," can safely boost a patient's T-cell count by two to five times -- more than in any previous treatment or combination of therapies. In a half-dozen trials conducted over the past two years involving almost 400 patients, scientists have been able to typically double the amount of immune system cells in people infected with HIV. In some patients, adding IL-2 restored immune system cells to levels similar to those of healthy, uninfected patients, something never before achieved.

The results are preliminary and more research must be done, but scientists and health officials who have reviewed the new data say the results so far are promising and impressive. Donna E. Shalala, secretary of Health and Human Services, whose National Institutes of Health had staff scientists running three of the latest studies, said in an interview that the new report suggests "the tantalizing possibility that we will one day be able to restore the damaged immune systems of people infected with HIV."

In one New England Journal of Medicine study out today, involving about 60 patients over three years, researchers managed to more than double the median T-cell counts in some patients to 916 -- near normal levels -- from 428 following 12 months of treatment of IL-2 combined with antiviral drugs such as AZT. Patients in the study who took AZT-like drugs without IL-2 showed a slight decrease in T-cells during the same period.

Healthy people have T-cell counts of about 1,000 cells per cubic millimeter of blood. Under attack from HIV, T-cells drop to 200 or below, leaving the body vulnerable to a wide range of life-threatening infections. While the latest cocktail therapy has succeeded in driving HIV in patients' blood down to undetectable levels, scientists say they must find a way to replenish T-cells destroyed by the deadly virus if they are to let patients stay healthy for many years.

In five of the patients in the journal study, the infection-fighting T-cells were kept at healthy levels for 18 months after the patients had stopped taking IL-2 as part of their antiviral therapy.

"To date, no combination of [antiviral medicines] has been shown to to be capable of inducing increases in [immune cells] of this magnitude or duration," according to the new report by a team of scientists at the National Institute of Allergy and Infectious Diseases, the agency charged with leading the federal government's attack against HIV.

IL-2 so far has been approved only for use against a rare cancer. It is marketed by Chiron Corp. of Emeryville, Calif., under the brand name Proleukin. It has taken years of study in the laboratory and in test subjects to figure out how precisely to use the engineered protein against AIDS, says Anthony Fauci, director of NIAID. He cautioned: "It's been a very long haul, and we're far from finished."

Indeed, numerous problems may keep IL-2 from widespread use, at least for a while. The drug must be injected into patients, usually during a five-day hospital stay every two-to-four months. Moreover, most patients typically experience severe flu-like symptoms and other side effects. IL-2 is also very expensive. Chiron officals say annual therapy might cost $3,000 to $5,000, depending on how much of the drug is used.

In addition, researchers say they are uncertain how long a patient's body can endure IL-2 therapy or how long the drug's benefits will last. Chiron and the NIH plan a series of larger trials soon to answer these and other questions.

Still, news of IL-2's potential has rocketed through the AIDS community in recent months. John Aubrey, who entered one NIH trial about three years ago, is an enthusiastic supporter. Mr. Aubrey, 36 years old and infected with HIV since 1983, joined the NIH study when his T-cells suddenly dropped to 160 from 500. For the first year of treatment of IL-2 alone, his T-cells rose slightly and then fell. But in January, researchers added Merck & Co.'s protease drug, Crixivan, to the mix. Mr. Aubrey's most recent T-cell count was 760.

"My health is excellent, better than in years," Mr. Aubrey says, although he says the IL-2 injections make him feel "terrible," with high fever, nausea, dizziness, migraines and short bouts of depression. "The effects usually take a few days to wear off," Mr. Aubrey says. "It requires a real commitment."

Based on the recent reports and personal testaments, some AIDS patients already are getting their doctors to prescribe IL-2, according to AIDS activists and Chiron officials. But some experts counsel against it. "At this time I would not recommend anyone use IL-2 except in a clinical-research setting," says Joseph Kovacs, the lead researcher of the New England Journal of Medicine report.

Martin Delaney, with the San Fancisco-based Project Inform, says that while he agrees that preliminary reports of IL-2 are "significant," he advises caution to those who ask about it. "The scientists are understandably excited," Mr. Delaney says. "But we still need long-term studies now showing whether this kind of therapy produces sustainable health benefits."

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