Here's an article from last week's USA Today. They also mention the fat build-up as a potential problem in long term treatment:
2/06/98- Updated 10:45 AM ET
Scientists shoot for zero HIV in patients
CHICAGO - Government researchers are quietly trying to rebuild the
immune system and eradicate HIV, the AIDS virus, from 100 to 200
human volunteers.
Underlying the experiments is a bold, risky, two-pronged strategy: Kill
the bulk of the virus with potent drugs, then flush latent HIV from the
dormant white blood cells that are its last sanctuaries - exposing the
lingering virus to lethal medication.
Will this work?
"The answer is not too far in the future," says Anthony Fauci, director
of the National Institute of Allergy and Infectious Diseases. Researchers
soon will begin analyzing the results of their work.
Fauci says extensive laboratory experiments have already provided
solid evidence that the approach might work. "I'm a fundamentally
conservative guy," he says, "but I'm enthusiastic about the concept."
This so-called "flush out" strategy has been a subject of much debate
for more than a year, ever since doctors recognized that the new
protease inhibitors could virtually wipe out HIV in the blood. Sensitive
new tests confirmed that the virus could no longer be found there.
But doctors knew that when patients stopped taking their drugs, which
prevent HIV from making copies of itself, the hardy virus would bounce
back, often fortified to resist antiviral medications.
New research has confirmed that traces of HIV lurked silently in
slumbering white blood cells. These sentinels, called resting T-cells or
memory cells, are created during an infection to recognize the microbial
interloper so that they can attack it if it turns up again.
HIV kills most of these memory cells, but not all of them. In their resting
state, these cells may survive for years. If the cells are infected with
HIV, HIV survives, too.
Then, when virus-laden memory cells awaken to fight off an invader,
HIV takes over. Using the cell's genetic machinery, it copies itself,
flooding the bloodstream.
To guard against rekindled HIV infection, patients must take a costly,
complex regimen of as many as 20 pills a day for life.
"I think it is unlikely we will ever eradicate the virus from infected
persons," W. Gary Tarpley, Pharmacia & Upjohn, Kalamazoo, Mich.,
told 3,500 scientists at a retrovirus meeting this week.
"That's a reasonable view, but to say that with any degree of certainty is
wrong. We don't know," counters David Ho of the Aaron Diamond
AIDS Research Center, New York.
The trouble is, no one knows how long the drugs, approved in 1996,
will work. HIV circulating in the general population already shows
some resistance to antiviral therapy.
Also, people taking protease inhibitors have begun developing severe,
unforeseen side effects that have prompted some, and forced others, to
quit taking the drugs. Among them: hyperglycemia, diabetes, and a
breakdown of fat metabolism that leads to the build-up of fatty deposits
around the waist, over the shoulders and, in women, in the breasts.
Clifford Lane and Joseph Kovacs, of Fauci's team, began the work that
led to the promising new experiments several years ago, before the
advent of the new antiviral drugs.
In early experiments, they began using an immune stimulant, known as
IL-2, to try to rebuild the HIV-ravaged immune system. When
protease inhibitors became available to researchers in 1995, they
added those drugs to the mix, hoping that they might also be able
eradicate the virus.
Half of the volunteers are taking Highly Active Retroviral Therapy, or
HAART, a combination of drugs including protease inhibitors. The rest
are getting HAART plus IL-2 to awaken dormant memory cells.
Once memory T-cells come to life, releasing virus, they quickly die off.
Antiviral drugs then can wipe out the last lingering traces of lethal HIV.
Fauci says the only side effects so far have been the flulike symptoms of
IL-2. Some doctors worry that IL-2 would unleash virus in the brain.
Because the brain is sheltered from toxins - and drugs - by the
blood-brain barrier, HAART could not reach it there. Then,
theoretically, the virus could attack the central nervous system or
spread elsewhere.
Fortunately, Fauci says,"We haven't seen any serious neurologic events
caused by the virus."
Unfortunately, the drugs do not work in everyone, so efforts to find
more potent medicines will continue. "We'll need new drugs whether or
not we find a cure," Ho says.
By Steve Sternberg, USA TODAY |
