30 Nov 2006

HIV treatment puzzle solved

Helping to end a longstanding clinical debate, a new study finds that stopping and then restarting HIV drug therapy doesn't work.

Not only are patients more likely to die of Aids when their antiretroviral treatment is interrupted, they are, surprisingly, also more likely to suffer drug side effects when therapies are resumed, the study found.

Experts had once speculated that giving patients "vacations" from the powerful drug cocktails might be of benefit.

Confirms present practice
However, the new trial "confirms present practice, in that most doctors still are of the opinion that once you start, you don't stop," said Dr Michael Horberg, director of HIV/Aids policy, quality and research at Kaiser Permanente Health Plan in Oakland, California.

"It looks like the benefits of continuing antiretrovirals in continuing to suppress levels of virus are large," added Dr Roy Gulick, director of the HIV Clinical Trials Unit at Weill Cornell Medical College in New York City. "What we have here are unanticipated toxic effects or non-HIV-related effects that are associated with stopping medications."

"What that does to the field is makes us rethink stopping the medications, really, in any clinical situation," Gulick said. Stopping and starting treatment is ill-advised not only because it promotes HIV progression but because of "the risk of other kinds of toxicities," he said.

When antiretroviral therapies were introduced, they represented a huge advance in the treatment of infection with HIV, the virus that causes Aids. However, the drugs do carry serious side effects, including major metabolic and cardiovascular complications. The therapy is also expensive, difficult to comply with, and can promote the development of resistant viral strains.

Experts have long debated whether the therapy could still be effective and less toxic if it were interrupted when CD4+ or T-cells - the killer immune cells that HIV destroys - rose above a certain level. In theory, patients might restart their therapy if and when CD4+ levels declined too far. A steady drop in CD4+ cells indicates that HIV infection is progressing to Aids.

How the study was conducted
To test that strategy, the authors of the new study, the largest of its kind, compared two treatment methods. In one group, doctors suppressed blood levels of HIV long-term by having patients continually take medication. The other group was placed on a "stop and start" regimen, depending on changes in their CD4+ levels.

The researchers randomly assigned 5 472 HIV-infected individuals who had a CD4+ cell count of more than 350 cells per cubic millimetre of blood to receive antiretroviral therapy either continuously or episodically.

Those in the episodic group only received treatment when their CD4+ count dipped below 250 cells per cubic millimetre, and continued receiving therapy until their count increased to more than 350.

Study stopped early
The study was designed to last six years but the results were so striking that it was halted after only 16 months. That's because patients in the episodic group were 2.6 times more likely to develop an opportunistic disease or to die of Aids than people in the continuous group.

Results of the study are published in the November 30 issue of the New England Journal of Medicine.

"There were more clinical events in terms of Aids episodes and deaths in the group that started and stopped, but, even more surprising was that there was also more toxicity, which is exactly the opposite of what they thought [would happen]," Gulick said. "That was an extremely important finding."

Added Dr Joel Gallant, professor of medicine and epidemiology and associate director of the Aids Service at Johns Hopkins University School of Medicine: "The strict interpretation is that you probably shouldn't interrupt therapy once you start and, if you do, you should restart it much sooner than 250. The broader interpretation would be that people are better off on treatment than not on treatment." – (HealthDayNews)