Newsday - February 4, 1999
Laurie Garrett - Staff Correspondent

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.
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