Study: HIV 'Drug Holidays' Don't Work

(WebMD)  HIV treatment interruptions don't work, a huge international clinical trial shows.

The strategy is known to scientists as "structured treatment interruptions," or STI. Patients have another name for it: drug holidays.

The idea is to put HIV treatment on pause once the powerful drug combination lets a person's CD4 T-cells — the immune cells under attack by the AIDS virus — return to higher levels. Treatment starts again when CD4 counts drops toward the danger zone.

It was hoped the strategy would cut back on the side effects — and cost — of HIV treatment. Scientists also hoped it would help the recovering immune system learn to fight the virus more effectively. The new findings dash those hopes.

In a study involving 5,472 people with HIV, those on interrupted therapy had a 2.6-fold higher risk of death from any cause or from HIV-related infection.

"The idea of a benefit of interrupted HIV treatment for long periods of time, where you allow the virus to bounce back, is not a valid strategy," Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, said at a news conference.

The trial, which began in January 2002, enrolled 5,472 HIV patients with CD4 counts of more than 350. Half took their drugs every day without fail. The other half took their HIV drugs only when their CD4 counts dropped to less than 250, then stopped treatment whenever their CD4 counts reached more than 350.

The trial was supposed to last six years but was stopped early when it became clear patients getting treatment interruptions were doing significantly worse. Not only did they have a greater risk of death, they also had a 1.7-fold higher risk of major heart, kidney, and liver disease.

This last finding was totally unexpected, as these events were thought to be side effects of HIV drugs. Instead, the higher risks to the treatment-interruption patients were due to higher blood levels of HIV and lower CD4 T-cell counts.

"We still have much to learn regarding the detrimental effects of uncontrolled HIV infection," write UCLA researchers Judith S. Currier, M.D., and Lindsey R. Baden, M.D., in an editorial accompanying the study in the Nov. 30 issue of The New England Journal of Medicine.

The treatment-interruption strategy used in this study isn't the only one being tried. Study researchers W.M. El-Sadr, M.D., and colleagues warn that these strategies must now be considered risky.

"The lack of benefit of our interruption strategy on major adverse events associated with antiretroviral therapy suggests that such strategies should be viewed as carrying a net clinical risk unless proven otherwise," El-Sadr and colleagues conclude.

SOURCES: El-Sadr, W. The New England Journal of Medicine, Nov. 30, 2006; Vol. 355: pp. 2283-2296. Currier, J. and Baden, L. The New England Journal of Medicine, Nov. 30, 2006; Vol. 355: pp. 2359-2361. News conference, HIV Summit, Nov. 29, 2006.

By Daniel DeNoon
Reviewed by Louise Chang, M.D