A DANGEROUS MIX REVEALED

HIV Therapy, Drugs A Danger

Chicago - HIV patients who use heroin, methadone or the recreational
drug Ecstacy risk complications with their medicines that could be
life threatening, scientists said yesterday.

Because these drugs are metabolized in the liver through some of the
same chemical pathways involved in processing commonly used anti-HIV
medicine, patients can risk either drug overdoses or sharp and
dangerous withdrawals, according to research reported at the sixth
Conference on Retroviruses and Opportunistic Infections held here
this week.

Given that drug abusers and methadone users comprise one of the
largest groups of AIDS patients in the United States, these findings
have profound implications, the researchers said.

In one study, Dr. Gerald Friedland of Yale University found that HIV
patients who take a powerful medicine called ritonavir have different
responses to heroin. Ritonavir's chemical effects on the liver causes
heroin to gush into the brain - an occurrence that, in some cases,
resulted in instant drug overdoses.

"We suggested to needle exchange programs in New Haven that people
should {be advised to} halve their doses of heroin if they're taking
ritonavir," Friedland's Yale colleague Dr. Frederick Altice said in
an interview. "People said, `Oh, cool! I'm not spending as much money
on heroin so I don't need to be breaking into as many houses.' "

The Yale group also determined that the medicine AZT tends to increase
the amount of methadone that gets to the patient's brain, while the
medicine ddI lowers methadone levels in the brain.

"There may need to be some dosage adjustments," Friedland explained.
"It's really hard to know what to recommend."

A British team, meanwhile, reported the case of a young man who was
taking ritonavir as a component of his HIV treatment, and died one
night when he ingested the mind-altering drug called Ecstacy. The
precise biochemistry of the interaction isn't clear, but the young
man's entire cardiovascular system shut down when ritonavir and
Ecstacy mixed in his body.

But Altice thinks the most extreme interaction is seen when methadone
and the anti-HIV medicine nevirapine are mixed. Altice noted the
response of a 22- year-old female patient on methadone who was doing
well on the drug and at her job. "She started {anti-HIV} therapy and
within two days suffered traumatic withdrawal symptoms," he said,
adding that the "sad thing was that she decided not to risk her
employment or withdrawal, so she stopped all {anti- HIV} drug therapy."

Altice said he's found he needed to increase narcotics doses tenfold
in HIV patients taking nevirapine in order to prevent methadone
withdrawals. Nevirapine appears to flush methadone out of the body,
but scientists don't yet know why. Sudden narcotics withdrawal is
physically and emotionally painful and can, in extreme cases, be life
threatening.

In 1985, while only an intern at Yale, Altice diagnosed his first HIV
case; a heroin-addicted female prostitute. Altice said the woman is
still alive, but that it's been a struggle that included severe
complications that cropped up between her methadone treatments and
her HIV therapy.

When Altice's patients started taking an anti-HIV cocktail that
included nevirapine two years ago, he said, the methadone flushed out
of her body and "she returned to heroine use." Since then, Altice said
he increased the woman's methadone dose tenfold, and she once again
was able to work on pulling her life together, despite her HIV.

"That's been the success story of her life," Altice said with obvious
pride. "She was living in a shooting gallery. Now she has a home and
gives community lectures."

Altice and Friedland reported this week on seven such cases of
methadone / nevirapine interactions. They noted in their presentation
that the manufacturers of anti-HIV drugs minimized the potential for
such interaction when they originally petitioned for federal
licensing, and didn't pursue the issue as the drugs were placed in
general use.

"We're the only ones who have looked at this," Friedland
said.