Study stopped as AIDS therapy deemed a failure

WASHINGTON — A major international study of a drug-conserving AIDS therapy has been halted because patients trying the on-again, off-again strategy got sicker than those who never took a break from the drugs, U.S. researchers announced Wednesday.

The study had enrolled more than 5,000 HIV patients in 33 countries before it was abruptly stopped by the National Institutes of Health after a routine safety analysis.

Researchers concluded that those who took their medicine only when their immune systems waned were more than twice as likely to get sicker or die as people who took the drugs every day.

The finding is a blow to AIDS advocates who had hoped drug-conserving therapy would reduce side effects — and save money on the expensive medications, particularly in the poorest countries, where AIDS is skyrocketing.

"All around, it's disappointing news," said Jose Zuniga, president of the International Association of Physicians in AIDS Care.

He cautioned that the idea of drug-conserving therapy should not be shelved permanently: It might work one day, when there are newer, even more potent anti-HIV medicines from which to choose.

"It should signal us to invest even more in developing the next generation of anti-retroviral drugs that may make this a possibility," Zuniga said.

Combinations of potent anti-HIV drugs help patients live longer and slow their progression from HIV infection to AIDS. But the combinations can cause serious side effects; it's inconvenient to take numerous pills a day, and the drugs are expensive.

While treatment guidelines back continuous therapy, earlier small studies had suggested it might be possible to take medication breaks and still control the virus while reducing side effects and cutting costs. The NIH funded a bigger study — one of the largest ever done with HIV therapies — to see if those results were real.

Volunteers were randomly assigned to take their medicine continuously or only when key immune cells called CD4s dropped to a certain level.

Not only did that strategy not control the virus, but there actually was an increase in side effects affecting the heart, kidney and liver in patients taking the drugs only episodically, the NIH said.

The increase in side effects was counterintuitive, and researchers so far can't explain it, said Dr. Sandra Lehrman of the NIH's AIDS division.

NIH officials last week notified doctors participating in the study to begin contacting their patients about the results, and to recommend full-time dosing for everyone who had taken intermittent therapy.

For such a large international study to so quickly find an answer — the first patients were enrolled in 2002 — is important, Lehrman stressed.

"This large international study showed the benefit of the viral suppression strategy," she said. The main message for HIV patients is if you're taking the drug cocktails, "It does not appear prudent to get off them."