HIV Drug Holidays Not a SMART Idea

NEW YORK, Dec. 1 -- HIV patients should not take drug holidays.

That's the unambiguous warning from researchers involved in the large, randomized Strategies for Management of Antiretroviral Therapy (SMART) study. The trial was halted early this year because patients in the drug holiday arm were doing significantly worse than those on continual treatment.

"The key message here is that treatment interruption should not be recommended, at least the way we used it," said Wafaa El-Sadr, M.D., of Columbia University here, one of the study's co-chairs.

Another co-chair, James Neaton, M.D., of the University of Minnesota, was even more pointed: "It just doesn't work," he said in an interview.

His advice to doctors and patients: "Don't do it unless you're part of a carefully designed research protocol. This is not something to play with or dabble with."

The SMART study, with 5,472 participants in 33 countries, was the largest trial to examine the idea of treatment interruption and had some surprising results, the researchers reported in the Nov. 30 issue of the New England Journal of Medicine.

Specifically, Dr. Neaton said, the researchers had expected patients in the drug holiday arm would have more opportunistic infections but fewer other adverse events, especially those usually associated with HIV medications.

Indeed, the primary endpoint of the study was to compare the incidence of opportunistic infections and death from any cause between the arms.

Surprisingly, the study found:

• Opportunistic disease or death from any cause occurred in nearly three times as many participants in the drug holiday group as in the continuous therapy group -- 120 versus 47.
• The hazard ratio was 2.6, with a 95% confidence interval from 1.9 to 3.7, which was statistically significant at P

"I don't think this closes the door on treatment interruption," he said, "but it does close the front door."

Coming in through the back door, he added, may be people who have "compelling reasons" to go on and off therapy. For instance, he said, women may wish to go on treatment during pregnancy to prevent mother-to-child transmission.

Dr. Baden added that because those in the drug holiday arm of the SMART study were on treatment less than a third of the time future studies might find that less time off medication might produce a better result.

But one of the key issues highlighted by the study, Dr. Baden said, is that uncontrolled virus -- regardless of a patient's CD4 cell count -- appears to have "deleterious effects," including increasing the risk of cardiovascular disease.

Many of the medications used to treat HIV have been linked to increased cardiovascular risk, he noted, but the SMART study hints that the virus itself may be responsible for some of the dangers.

"The fundamental message." he said, "is that when you meet the criteria for treatment, continuous treatment is the way to go."