A intense area of AIDS research involves the on-again, off-again use of powerful anti-viral drugs. Scientists want to find out whether the interruption of anti-viral therapy jump starts a patient's natural immunity to fight HIV, the virus that causes AIDS.
The idea for on again, off again therapy - known by experts as structured treatment interruptions - came from a less than scientific source. Bernard Hirschel is head of the HIV/AIDS unit at the Geneva University Hospital in Switzerland.
Dr. Hirschel says AIDS patients themselves began taking periodic holidays from anti-retroviral drugs. The reason: those infected with the AIDS virus must take three or more anti-retroviral drugs, three times a day and the medications can cause unpleasant side effects, including vomiting and diarrhea. "They found it unbearable to continue taking the drugs, and were looking for ways to keep a therapeutic benefit with less drugs," he said. "From that, there are many people who say that treating patients for 30, 40 years is not an option so we have to think of ways to do with less."
Dr. Hirschel was part of an international team of Swiss and Spanish researchers that conducted the largest study ever of structured treatment interruptions.
The periods during which patients are off treatment vary in different clinical trials. In the latest study, reported in the journal Proceedings of the National Academy of Sciences, 130 patients were placed on a combination of anti-AIDS drugs for eight weeks, then they were taken off the drugs for two weeks. The patients went through four drug treatment cycles followed by the same number of periods when they were drug-free.
After forty weeks, all therapy was stopped to see whether the patients' natural immunity kicked in to fight the AIDS virus.
The concept is called auto-vaccination. The idea, say experts, is to see whether a patient's compromised immune system, by being periodically exposing to small amounts of HIV, might come to life instead of having no chance to fight an HIV infection as a result of being constantly suppressed by anti-retroviral drugs.
Dr. Hirschel says viral levels in the vast majority of study participants went back to where they were before the structured treatment interruptions. "So, the idea that auto-vaccination would keep viral levels at a very low level is not what happened," he said. "That is if you want the bad news. The good news is in our trial, many patients did quite well for many months without treatment - up to a year or more - and that there was not development of treatment resistance. In other words, if you treated those patients again, those patients still responded to the old drugs."
Dr. Hirschel says about 40 percent of patients were able to complete the trial. The rest had to drop out because their viral levels began to climb or they experienced a decline in immune function, and they had to begin treatment again.
Ume Abbas is with the University of Pittsburgh's Division of Infectious Diseases. Dr. Abbas notes there have been a number of smaller studies of structured treatment interruptions, with mixed results.
Dr. Abbas says the latest study is by far the most conclusive, calling interruption therapy "risk without reward" for several reasons. First, the amount of lethal AIDS virus in their blood can rebound without anti-retroviral drugs, causing infected patients to become sick, as some did in the latest study. "The benefit you accrued over years of anti-retroviral therapy by trying to eliminate the cells that contain the virus may be lost," said Ume Abbas. "And then the third risk is these patients in whom you interrupt therapy, the viral load is very high, so there is a very high risk of HIV 1 transmission."
On the plus side, experts agree that on-again, off-again treatment with expensive anti-retroviral drugs could make those drugs more accessible to people in poor countries. That is, if and when an effective drug regimen is found.