Widely heralded new AIDS treatments that seemed to stop the virus’s advance and revive patients from near death are beginning to fail in about half of all those treated, doctors said Monday.
The disappointing reports suggest the tough virus is coming back after being knocked briefly into submission, just as many experts feared it would.
“Over the past year, we had a honeymoon period,” said Dr. Steven Deeks. “The epidemic will likely split in two, and for half the people, we will need new therapeutic options.”
Deeks presented data from the University of California at San Francisco’s large public AIDS clinic at San Francisco General Hospital.
Prescriptions of so-called three-drug cocktails - two older AIDS drugs plus one of the new class of medicines called protease inhibitors - clearly have revolutionized AIDS care. In many places, more than 90 percent of AIDS patients are taking these combinations, and typically people start on them as soon as they learn they are infected, even before they get sick.
Patients whose disease-fighting T cells were ravaged by HIV have gotten out of bed, regained normal lives and even gone back to work. However, many worried from the start that the virus would eventually grow resistant to the protease inhibitors and resume its insidious destruction.
The latest data, presented Monday at an infectious disease conference sponsored by the American Society of Microbiology, suggests this is indeed happening regularly.
Deeks and colleagues reviewed the records of 136 HIV-infected people who started on protease inhibitors in March 1996, when Crixivan and Norvir, the first two powerful protease inhibitors, came on the market.
Most patients responded dramatically. Their virus levels dropped so low they could not be found on standard tests. But since then, the virus has returned to detectable levels in 53 percent.
Although this is ominous, no one knows exactly what it means.
“All of our ‘failures’ are clinically feeling very well,” said Deets. “It’s very important to understand we have no idea of the prognosis of people who have resistant virus.”
Deets said other large AIDS clinics are having similar experiences, although his is the first to present the data publicly.
“There is a whole mixture of explanations” for the failures, said Dr. David Ho of the Aaron Diamond AIDS Research Center in New York City.
Ho said that for people who had relatively low virus levels when they started taking the drugs and had not used other AIDS medicines, failure almost always means they did not take their pills on schedule. Even missing a few doses can ruin the treatment.
“Compliance is absolutely critical,” Deets said. “When we say compliance, we mean rigid adherence to over 20 pills a day.”
Also at high risk of failure are those who were on other AIDS drugs before starting protease inhibitors or whose T cell counts were very low.
Deets said his data are far different from the carefully controlled drug experiments sponsored by pharmaceutical companies to demonstrate the medicines’ potential. These studies show far more encouraging results.
Among the longest-running of these is a study of 28 patients who have been taking Crixivan, AZT and 3TC. Dr. Roy Gulick of New York University said Monday that after almost two years, the virus is still undetectable in 22 of them, or 79 percent.
Deets said real-world experience is not as promising as the trials because patients in the studies are less sick to start with and more highly motivated to scrupulously follow their drug regimens.
Also presented Monday was the first large study of the use of protease inhibitors in children. Just over half appeared to be responding well after three months of therapy.