[Ip-health] Death rates higher with interrupted AIDS treatment

[Ira Glazer]

http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2006/11/30/MNGFMMMBAB1.DTL&type=printable

Death rate higher when AIDS treatment is erratic   Study a blow to idea
of managing HIV by monitoring white cells

Sabin Russell, Chronicle Medical Writer
Thursday, November 30, 2006

AIDS patients who stop taking their antiviral drugs whenever blood tests
show their HIV infection is under control run nearly twice the risk of
dying as those who take their medication without interruption, according
to a large international study meant to settle the question of whether
the practice is safe.

The experiment that eventually involved patients in 33 countries began
in January 2002 and was halted at the beginning of this year after
preliminary results showed that death rates were dramatically higher
among those who interrupted their drug treatments.

A safety monitoring committee decided that it would be unethical to
continue the experiment another four to five years as scheduled.

The study team led by the National Institutes of Health reports in
today's New England Journal of Medicine that the 2,720 patients in the
treatment-interruption group were 1.9 times more likely to die than
those in the like-sized group who took antiviral drugs every day, as
prescribed.

Those in the treatment-interruption group also ran a substantially
higher risk of becoming ill from infections that exploit the immune
system when it is weakened by HIV, the virus that causes AIDS.

The findings are bad news for those who hoped it was possible to manage
HIV disease by carefully watching CD4 counts -- the level of
infection-fighting white blood cells -- and taking the antiviral drugs
only when that level fell to a threatening low level. Such treatment
interruptions, in theory, could save billions in medical costs and spare
patients the unpleasant, and sometimes lethal, side effects of AIDS drugs.

"For practical purposes, it is the end" for that strategy, said Dr.
Anthony Fauci, director of the National Institute for Allergy and
Infectious Diseases, which bankrolled the study. It was called the
Strategies for Management of Antiretroviral Therapy, or SMART, trial.

Researchers who analyzed the data from the curtailed experiment made
some surprising discoveries. Although 55 patients in the
treatment-interruption group died, compared with 30 in the group that
maintained the drug regime, only 8 percent of all deaths were caused by
the classic opportunistic infections associated with AIDS.

The most common known cause of death was cancer, followed by
cardiovascular disease and substance abuse.

UCSF researcher Dr. Donald Abrams, who enrolled about 100 patients from
the Bay Area in the study, said it was difficult to generalize why more
people died in the treatment-interruption group because the actual
number of deaths was low. One possibility, he said, is that the virus
itself, or the inflammation it causes, can harm patients in ways not yet
fully understood.

Patients who interrupted treatment stopped taking their drugs if their
CD4, or T-cell, counts were above 400. Patients with that level of
infection-fighting blood cells do not typically show symptoms of
illness. A T-cell count of 800 or more is considered normal.

If their T-cell counts slipped below 250, the patients would restart
their drug therapy, stopping it when their counts went up to 400 again.
On average, those who stopped taking drugs remained off the medication
for 16.8 months. Those in the treatment-interruption group as a whole
were on HIV medication one-third of the time during the experiment.

Hank Wilson, a San Francisco AIDS activist and long-term survivor of the
disease, said it is too early to declare treatment interruption a
failure. He uses his own treatment-interruption plan, which he would not
disclose because, he said, what works for him might not work for others.
He remains healthy, with a T-cell count of over 800. It once hit a low
of 26.

Wilson noted that the overwhelming majority of patients in the study who
interrupted treatment did not have ill effects. He believes that the
data need to be examined more closely -- to determine, for example, if
those who stopped treatment and experienced a sharp increase in the
virus in their bloodstreams may have been using cocaine. The drug has
been shown in laboratory studies to accelerate HIV proliferation.

"It's like pouring gasoline on a fire,'' Wilson said.

Drs. Judith Currier and Lindsey Baden of UCLA wrote in an accompanying
article that the findings of the SMART trial were "definitive," but said
there may be some circumstances where treatment interruption is appropriate.

One such instance would be when HIV infection is caught early, in the
acute phase shortly after a patient contracts it, they said. These
patients could live for years before the virus begins to wear down their
immune systems, so it might make sense to stop the drugs after the acute
infection is treated.

Women who take AIDS drugs before and after childbirth, but whose T-cell
counts are high, might also be considered candidates for a
treatment-interruption study, Currier and Baden said.