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Antiviral Cocktail: The Toast of AIDS Researchers : Medicine: Experts at Costa Mesa conference believe attacking HIV with three drugs simultaneously will keep it from replicating and add years to patients’ lives.

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TIMES STAFF WRITER

Researchers hope to add years to the lives of AIDS patients by combining as many as three antiviral drugs and using new medications that ambush the virus in novel ways, experts said at a regional HIV conference Monday.

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The complexity and ever-changing nature of the human immunodeficiency virus render magic bullets and miracle cures unlikely, said experts at the eighth annual HIV/AIDS on the Front Line Conference in Costa Mesa, which was attended by about 1,000 physicians, health care workers and others.

But speakers expressed optimism that the 15-year scourge may be controlled little by little by piecing together what has been learned through painstaking basic research and clinical trials.

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“We haven’t found ways to eradicate the virus,” said Dr. Thomas C. Cesario, dean of UCI’s College of Medicine, “but we are finding better ways to suppress (it.)”

In the past few years, for example, researchers have found that combining AZT with one other antiviral drug--such as ddI or ddC--prolongs the effectiveness of the treatments.

Now, they speculate that using a third drug--one that attacks the AIDS virus in a different way--may prolong the effectiveness of treatment even further. These drugs include so-called protease inhibitors, which keep the virus from replicating by interfering with its production of essential proteins.

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Until now, drugs have been designed to interfere with an enzyme called reverse transcriptase that allows the virus to reproduce its genetic machinery.

The advantage of using three drugs together is that “the virus would have to mutate to be resistant to all three,” said Dr. Donald Forthal, an assistant professor of medicine at UCI who specializes in infectious diseases. “In fact, mutations that increase resistance to one (drug) may reverse resistance to another.”

Also, the various mutations may render the virus less effective at replicating, Forthal said.

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Using a combination of drugs may lessen each drug’s side effects--if lower dosages are used--allowing patients to tolerate the therapy better.

Early indications are that protease inhibitors, now in clinical trials, are somewhat more effective than other treatments, said Dr. Hung Fan, a professor of biology and virology at UCI.

The drugs appear to initially reduce the viral load--or quantity of virus in the blood--by 99% and, though it begins to climb again, it does so more slowly than under treatment with AZT and other drugs like it, Fan said.

At the same time, he said, the protease inhibitors seem to help patients rebuild their count of CD4 cells, a type of white blood cell whose depletion is characteristic of AIDS, he said.

Apparently, Fan said, when the virus mutates to escape the protease inhibitors, it does not replicate as well as it did before.

Another promising drug, Fan said, is Interleukin 2, a protein that also stimulates the growth of CD4 cells. Researchers reported this month in the New England Journal of Medicine that six of 10 patients had significantly improved CD4 counts under treatment with the drug.

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Fan cautioned that the drug appears to work only in patients with less advanced disease--with CD4 counts greater than 200 per milliliter of blood--and that it was given on a staggered basis. The risk of the drug, which is not an antiviral agent, is that it seems to “activate the virus” by promoting CD4 growth. That is why it must be used in combination with drugs that inhibit viral replication.

Also, Fan said, Interleukin 2 can cause serious side effects--similar to a bad case of the flu--and is very expensive.

“Whether this is going to develop into a common therapy, I don’t know,” he said.

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