San Francisco Chronicle - Thursday, August 27, 1992

The trial was directed by Dr. James Kahn of the University of California at San Francisco and involved 913 volunteer patients at 10 medical centers. The results are being published today in the New England Journal of Medicine.

To Kahn, the results suggest strongly that people who have taken AZT as long-term anti-viral therapy should consider switching to ddI, also known as didanosine, even though they have developed no side effects from AZT. "It's very satisfying to know that we now have an effective drug that provides another treatment option for many patients with ARC or others who are infected with HIV but are still without symptoms," he said.

THE VOLUNTEERS

Among the volunteers in the trial, some already were seriously ill with AIDS-induced infections; some showed early symptoms of the disease in a condition termed AIDS-related complex, or ARC; and the rest were infected with HIV, the virus that causes AIDS, but showed no symptoms of disease even though their immune systems were weakened. All the volunteers had been taking AZT for at least 16 weeks and were tolerating the drug well.

Half the patients were randomly assigned to switch to ddI at either low or relatively high doses, while the others continued taking AZT during the rest of the trial.

The results showed that 41 percent of the patients who continued taking AZT developed severe new opportunistic infections or died during the trial and its 18-month follow-up.

Among those who switched to low doses of ddI, only 32 percent incurred new complications or died, although high doses proved less effective.

The low-dose ddI volunteers also showed significant but temporary improvements in the numbers of their immune system cells, which often drop rapidly after HIV infection.

NO DIFFERENCE WITH FULL AIDS

Among the patients with full-blown AIDS diseases, however, there was no difference between those who stayed on AZT and those who were given either dose level of ddI.

But for the volunteers who had ARC or who were infected without symptoms, the benefits of switching from AZT to low-dose ddI were highly significant, the results showed.

In the trial, the patients were given ddI at two dose levels -- 750 milligrams a day and 500 milligrams a day. It turned out that only the 500-milligram dosage was effective. Kahn noted in an interview that because of the way the drug was administered, the 500-milligram dosage was equivalent to 400 milligrams of ddI given in tablet form -- or two 100-milligram tablets twice a day, the way doctors now prescribe it. AIDS DRUGS AND SIDE EFFECTS

Although there are many drugs to treat the opportunistic infections of AIDS, a major problem has been finding new drugs that attack the virus and prevent it from replicating without severe toxic effects to patients. Of these, AZT, ddI and a third drug known as ddC have now been approved by the federal Food and Drug Administration for full or restricted use.

All three, known as nucleoside analogs, work by disrupting the genetic machinery of the HIV virus so it cannot reproduce after it infects the cells of the immune system. All three drugs, however, have serious side effects, and for many patients none can be taken for long periods before it loses its power to fight the virus.

AZT, for example, suppresses the development of bone marrow and can cause severe anemia. On the other hand, ddI can cause severe inflammation of the pancreas and painful nerve damage.

Kahn at UCSF and many other researchers are looking at other strategies involving these drugs. One study, for example, is looking at the possible benefits of combined anti-viral therapy, with patients taking both ddI and AZT simultaneously. Another is recruiting volunteers who would alternate the two drugs, switching back and forth for given periods of time.

QUESTIONS REMAIN

But there remain many questions in the use of ddI and AZT, as Dr. Jerome Groopman, a noted AIDS researcher at Harvard, notes in an editorial on the Kahn report in today's New England Journal of Medicine. Teaming up with Dr. Jean-Michel Molina of the Saint Louis Hospital in Paris, Groopman cautions that issues of "anti-viral potency, drug toxicity, the emergence of viral resistance and the immune status of the host" all remain unresolved in assessing the ultimate benefits of the two drugs.

They warn, however, that "there are as yet no data to support the use of didanosine alone as the initial therapy in patients with advanced HIV infection."

A new trial is being planned to compare the benefits of ddI and AZT as the first drug to be used after HIV infection is detected.

Always watch for outdated information. This article first appeared in 1992. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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