DEVELOPING DRUGS ATTACK AIDS
By Daniel Haney
AP 25 Feb. 2002
Seattle -- Medicines are in development to attack the
AIDS virus in entirely new ways, including several designed
to keep HIV from ever gaining entry to the cells it kills.
The goal: Find alternatives to the drugs already on the
market, which lose their punch over time as the virus
develops mutant forms that are oblivious to them.
"All the currently available drugs are losing their
impact. There is obviously room for improvement," said Dr.
Douglas Richman of the University of California at San
Scientists gave their status reports on this arms race
Monday at the Ninth Annual Retrovirus Conference.
"Resistance remains a formidable problem," said Dr.
Richard Colonno of Bristol-Myers Squibb. "We can try to
stay ahead by coming up with the next generation of drugs.
But in the end we will likely lose that race. The advantage
of new classes of drugs is that they will work against all
the currently resistant virus. You are resetting the
While work continues on new versions of the standard drugs
already sold, much of the interest is in one new approach
-- blocking HIV from entering the blood cells in destroys.
"This will be remembered as the year of the entry
inhibitor," said Dr. Robert Schooley of the University of
Entry of the virus into the cell is a three-step process,
and drugs are in the works to gum up each of these. First,
the virus attaches itself to a molecule on the surface of
cells called CD-4. Then it hooks onto another called CCR5.
Finally it fuses with the cell and squirts its genes
One drug that attempts to block this first step is
Bristol-Myers Squibb's experimental medicine, code-named
BMS805. The drug works by covering up the spot on the virus
that sticks to CD-4. In the test tube, it appears to work
against strains of HIV that can resist all the other AIDS
drugs. However, it has not yet been tried on people.
Another drug, SCH-C, developed by Schering Plough, blocks
the next step in viral entry, the attachment to CCR5. In a
pilot study of 12 people, the drug used alone for one week
dropped viral levels dramatically.
Furthest along in testing is Roche's and Trimeris's T-20,
which blocks the third step of viral entry, fusion of HIV
to the cell. Large-scale studies are under way, and the
company says it hopes the results will enable it seek Food
and Drug Administration approval later this year.
All of the drugs now on the market block one of two enzymes
the virus uses to incorporate its genes into cells and use
them to reproduce itself. These chemicals are called
reverse transcriptase and protease.
A new drug reported at the meeting, developed by Shionogi &
Co. of Japan, attacks another of these enzymes, called
integrase. Dr. Tamio Fijiwara said the drug looks effective
in test tube studies, and initial experiments on people are
Scientists are also working on a variety of new versions of
older classes of drugs. Among these are medicines known as
non-nucleotide reverse transcriptase inhibitors.
Researchers presented data on one of these, developed by
Tibotec-Virco, that appears to be especially potent in
initial testing. The drug was designed to work against
viruses that are already resistant to Sustiva and Viramune,
two widely used similar drugs.
In initial testing, Dr. Joep Lange of the University of
Amsterdam said the drug alone appeared to work as well as
an especially powerful five-drug combination during the
first week of use.
"After a lull of two or three years, these data are very
exciting," Dr. Brian Gazzard of Chelsea and Westminster
Hospital in London said Monday's reports. "It's a phase of
accelerated development that is likely go on keeping pace
with the problem" of drug-resistant viruses.