The San Francisco Chronicle - Wednesday, July 12, 2000
Sabin Russell, Chronicle Staff Writer

Four years after American AIDS patients began taking combinations of three powerful anti-viral drugs that quell the relentless replication of HIV, patients weary of unpleasant or debilitating side effects are desperately seeking ways to take a break from the rigorous pill-taking that restored their health.

Top AIDS researchers yesterday presented early findings from carefully designed trials of "structured treatment interruptions." Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Disease, said the results are somewhat encouraging. But with so many unknowns, he warned patients contemplating a break in therapy: Don't try this at home.

"I would urge you not to try this until the clinical trials are complete," he said during a plenary session yesterday. The two biggest unknowns clouding treatment interruptions are whether the strategy will keep working over time and whether the virus will take advantage of breaks in therapy to mutate into drug-resistant forms.

Among the treatment interruptions being tested is a regimen in which patients take anti-viral drugs for a week, then take nothing for another week, in continuous on- and-off cycles. A second test puts patients on the drugs for two months, followed by one month off.

The encouraging news is that "the virus is going nowhere," said Fauci, although he stressed that the studies involve very small groups of patients. After seven cycles in the one- week-on, one-week-off trial, there was no evidence of significant increase in the amount of virus in the body, Fauci said. In the two-months on, one-month off trial, there was clear evidence that the tenacious bug begins replicating, but restoration of the treatments knocks the virus down to undetectable levels again. "Thus far, we don't seem to be getting resistance," Fauci said.

In the San Francisco Bay Area, activists are not waiting for the National Institutes of Health to finish their work. After consulting with their doctors, individuals are taking themselves off anti-retroviral therapy in similarly structured programs.

"People are doing this not because they want to stop taking the drugs, but because drug toxicities are reaching a point where they can't continue to take the drugs," said Jeff Getty, president of the board of Survive AIDS. The San Francisco advocacy group has begun gathering anecdotal reports from patients throughout the country who have taken themselves off the drugs for brief cycles.

Getty said the activists are not seeking drug company support for their experiment because they believe the firms have an inherent interest in seeing it fail. If patients found it was safe to switch to taking AIDS drugs only every other week, "we would cut the cost of these expensive drugs in half overnight," he said.

In this respect, the effort by American activists to cut AIDS drug consumption is not at all at odds with the goals of activists who want expanded access to the medications. The primary barrier to drug access in developing nations is price.

Hank Wilson of San Francisco has taken himself off his anti-viral drugs, closely monitoring the level of virus in his bloodstream. When his "viral load" starts to climb, indicating the virus is replicating again, he goes back on the drugs. He feels better under the new regimen.

"My doctor tells me I'm gambling," said Wilson. "I know that it is a crapshoot. I'm convinced there is a right and wrong way to do it." Wilson directs the anecdote-gathering effort known as the Berlin Patient Project. It is named after an anonymous German AIDS patient who took himself off drug therapy because of health problems, then returned to it, then stopped again -- only to find that he had cleared the virus from his system. He has been off drugs for four years, and although he has the virus in his system, his own immune system seems to be keeping it in check.

University of California at San Francisco virologist Dr. Jay Levy said the biggest problem with drug- interruption therapy seems to be that once the drugs are stopped, the body's own immune system does not kick in to take their place. "The question," said Levy, "is how do you get the immune system to come back?"

Levy said treatment interruption is a logical therapy to study, but it is fraught with danger. "There is no way I would advocate doing this until the clinical trials are over," he said.

Levy is especially wary of the one- week on, one-week off regimen. It causes patients to have "suboptimal" doses of drug in their system, conditions that are ripe for breeding drug-resistant strains of the virus, he said.

In dozens of sessions throughout the day yesterday, researchers discussed different strategies for fine- tuning the three-drug combination therapies. Increasing viral resistance remains a serious problem, forcing clinicians to switch drug regimens for their patients. A paper by researcher Dr. Scott Holmberg of the Centers for Disease Control and Prevention found that patients were most likely to have long-term success with anti- viral drugs -- a year or more without developing resistance -- on their first experience with the triple-combination drug therapy. About half the patients in his study reached that goal. The success rate fell to 30 percent for patients on their second course of combination drugs, and to only 15 percent after they were switched a third time.

Most successful with the treatment were those who had never taken any anti-retroviral drugs in the past, and who took the combination with only one form of drug known as a protease inhibitor. Those who took two protease inhibitors in their drug combinations did not fare as well.

Two other CDC studies found that drug resistance is cropping up as a problem in developing countries where the drugs are being tested in pilot programs. A study by Dr. Paul Weidle found resistance to at least one anti-retroviral drug in 74 percent of samples taken during a 20-month trial.

E-mail Sabin Russell at russells@sfgate.com.

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