Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adult

Jul 19 2006

A new analysis of existing research offers confirmation that taking a break from AIDS drugs is a bad idea for HIV patients with uncontrolled cases of the disease.

AIDS drug treatment interruptions - or "holidays" - have been the topic of much debate in the HIV treatment community over the past several years.

But the overwhelming majority of evidence suggests "greater harm than good" from treatment interruptions, said Nitika Pant Pai, M.D., a doctoral candidate in epidemiology at the University of California at Berkeley and lead author of a new Cochrane Library review. "There is no evidence as of now, to support their use outside of controlled clinical trial settings," she said.

Interruptions in drug treatment may seem counterintuitive when the goal is to reduce the symptoms of a disease. But doctors sometimes consider them for patients with chronic diseases.

Among other things, some argue that treatment vacations can improve quality of life by reducing side effects from medication and make it easier for patients to stick with the drugs once they return to taking them, Pai said.

AIDS drugs were once notoriously difficult to take, causing a variety of side effects and requiring a significant amount of juggling. Some pills had to be taken at specific times in regard to meals, and some had to be refrigerated; many patients took a huge array of pills each day.

In recent years, AIDS regimens have become easier to tolerate, and a three-pills-in-one drug is on its way to pharmacy shelves. Still, AIDS drugs continue to cause side effects such as nausea, and doctors worry they contribute to heart problems by boosting cholesterol levels.

Stopping treatment may seem to be an especially bad idea in patients whose HIV isn't under control, but doctors wonder if it might actually help them by halting the development of drug resistance. Then, the theory goes, patients could be put back on another regimen and be better equipped to avoid developing immunity.

The idea is to "wash out the resistant strain," said Calvin Cohen, M.D., an AIDS specialist and research director with Community Research Initiative of New England.

In their review, Pai and colleagues examined and critiqued 17 studies of treatment interruptions in patients whose HIV wasn't controlled.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Eight of the 17 studies were randomized controlled trials, considered the gold standard of medical research. In such studies, two or more groups are randomly assigned to different treatments; in most of the eight HIV studies, the people who assessed the results were blinded to which group was which.

The researchers found no evidence that treatment interruptions are helpful. In fact, some of the studies suggested that they may make HIV infection worse by allowing the immune system to deteriorate and the disease to progress.

In an earlier review published by The Cochrane Library, the researchers found that the "vast majority" of evidence suggests that treatment interruptions are also a bad idea in patients whose HIV is suppressed by drugs. In other words, those who beat back the disease with the help of drugs shouldn't take a break from them.

The researchers plan a future review that will look at the wisdom of treatment interruptions among newly infected HIV patients.

According to Cohen, doctors are still exploring whether treatment interruptions might have some value. While the findings so far haven't been promising, the fact is that some AIDS patients will go on treatment holidays on their own, he said.

"There are enough patients who look at 50 years of taking pills every day" and simply choose to stop taking them, he said. The question is this, according to Cohen: "Is there a way to minimize the harm of staying on (the drugs) while minimizing the harm of going off (them) entirely?"

One approach is to see how patients do when they take weekends off from their drug regimens, Cohen said: "What flexibility do we have with our medication?"

For now, however, Cohen agrees with the findings of the two reviews: "The conclusion of the moment is that we do not have a treatment interruption approach we can recommend."

By Randy Dotinga