From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: AZT-ddI Article in SF Chronicle
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6043
Organization: unspecified
Date: Fri, 28 Aug 92 08:53:54 PDT

The following article is from the Thursday, August 28, 1992, San 
Francisco Chronicle.

This article is not copyrighted.
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DDI CAN BE BETTER THAN AZT, TEST SHOWS

New Drug Looks Most Useful For Those Merely Infected Or With Early Aids 
Symptoms.

By David Perlman

Patients infected with the AIDS virus or in the early stages of illness 
suffer fewer AIDS-related complications and improve their immune systems 
by switching from the anti-viral drug AZT to a newer drug known as ddI, 
according to a nationwide study.

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.

Among the volunteers in the trials, 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 number of their immune system cells, which often 
drop rapidly after HIV infection.

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 not prescribe it.

Although there are many drugs to treat the opportunistic infection 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 infect 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.

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.
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Newsgroups: sci.med.aids