An entirely new class of AIDS drugs
on the horizon may offer just-in-time help to many patients whose
treatment options are running out, researchers said Thursday.
The latest data suggest these drugs may dramatically restore
health - at least temporarily - to people dying because the virus
has grown resistant to all the currently available AIDS medicines.
The new drugs block HIV in a different way from the standard
medicines that have revolutionized AIDS treatment in recent years.
Instead of gumming up the virus's ability to manufacture new copies
of itself, they block the virus from getting inside blood cells.
The drugs are called entry inhibitors and are being developed by
many companies, although only one has entered broad human testing.
"They hold significant promise for the treatment of HIV," said
Dr. Joseph Eron of the University of North Carolina.
Doctors discussed the drugs at the 13th International AIDS
Conference, where the latest data were presented on Trimeris,
Inc.'s experimental T-20, the most advanced medicine in the field.
Combinations of drugs introduced about five years ago turned
AIDS from a death sentence to a treatable disease, at least in
parts of the world where people can afford the medicines. These
combinations can drive the virus below detectable levels, but in
about half of patients, the virus returns within a year.
When this happens, doctors switch their patients to different
combinations of the 14 available drugs. However, the virus usually
returns even more quickly with each new drug cocktail.
Most of these people remain outwardly well, despite their virus
levels. But no one knows how long this will last, and doctors worry
they will be left with nothing to fight the disease.
"We desperately need new targets for tackling HIV," said Dr.
Julio Montaner of the University of British Columbia. "We think
these people will need help in the not too distant future."
The current drugs fit into three major classes. But all work by
blocking the virus's ability to make new copies of itself once it
infects a cell. The new drugs instead are designed to stop the
virus from penetrating cells to start this process.
When the new drugs are used alone, the virus appears to quickly
grow resistant to them, just as it does with other medicines. So
doctors envision combining these so-called entry inhibitors with
the standard medicines to keep a step ahead of the virus.
"Drugs that work on the outside of the cell would be a
tremendous addition to the drugs that work on the inside," said
Dr. David Ho of the Aaron Diamond AIDS Research Center in New York
Dr. Cal Cohen of the Community Research Initiative of New
England presented data on 71 patients who took T-20 after failing
with all the standard drugs. Fourteen did not get better, and 16
others dropped out of the study for a variety of personal reasons.
But after one year, 41 are still in the study and responding well
to the treatment.
Their average virus levels were 100,000 copies per milliliter of
blood before treatment and 3,000 copies now.
Among the patients was a dying man, blind in one eye from an
AIDS-related infection, whose HIV-ravaged white blood cells had
dropped to a precipitous 33 copies per cubic millimeter of blood.
After a year on T-20 and four standard AIDS drugs, his blood cells
have risen to 430 copies, and his virus level is barely detectable.
"Now he is even healthier looking than I am," Cohen said.
"He's back to life. You control the virus, and good things
The drug's major drawback is that it must be injected twice a
day, but Cohen said patients seemed able to do this without
Fusion inhibitors, plus new versions of standard drugs, "may be
exactly what people need," Cohen said.
Trimeris is designing large, final-stage testing of T-20.
Officials say this will involve people at earlier stages of
In recent years, scientists have worked out the mechanics of the
devilishly sophisticated process by which the virus gets into its
targets. T-20 works by blocking one step in the fusion of the virus
to cells, and other drugs interrupt at other points.
Another of these entry-blocking drugs, developed by Schering
Plough, begins first-stage human testing this month in the United