San Francisco Chronicle - Thursday, August 28, 2003
Sabin Russell, Chronicle Medical Writer

Researchers found that patients who temporarily stopped taking their AIDS drugs and then switched to new ones were more than twice as likely to have their illness take a turn for the worse, compared with those who kept taking their medications.

The results were so discouraging that researchers stopped enrolling patients in the clinical study a year ago. Those who took drug holidays experienced a precipitous drop in infection-fighting white blood cells, making them more vulnerable to infections that ultimately sicken and kill AIDS patients.

Researchers have been following the health of the 270 participants ever since. Their report on the experiment is published in today's issue of the New England Journal of Medicine.

"This is clearly one instance where treatment interruption is not warranted, " said Dr. Jody Lawrence, a UCSF AIDS specialist at San Francisco General Hospital and lead author of the study, which was funded by the National Institute of Allergy and Infectious Diseases and conducted at 16 clinics across the United States.

Because of the cost and toxic side effects of AIDS drugs, thousands of patients who have been battling the disease for years decide to take drug holidays without clear scientific proof whether these breaks help or harm them.

Doctors said the latest study should give them pause.

Complicating the decision, however, are the results of an earlier French study, which showed nearly the opposite effect. In fact, that study was halted before completion because the results were so favorable it was deemed unfair to deny the drug holiday to the control group. However, the French study involved about half as many patients as the UCSF study, reducing its statistical value.

"What are clinicians to do, when faced with studies with divergent results . . .? They must go with the results of the large study," wrote Swiss infectious disease specialist Dr. Bernard Hirschel, in commentary accompanying today's report.

The jury is still out as to whether some forms of drug holiday might work, but the latest study casts serious doubt about using the technique among those patients infected with a virus that is resistant to more than one drug.

The hope was that a break in treatment would permit the resurgence of the original strains of HIV, which were effectively treated with older types of AIDS drugs, and could be controlled again when treatment resumed.

Tests proved that those who halted their drug treatment did, in fact, see a rebound of the older strains of HIV, which are considered to be more biologically "fit" than the mutant strains that develop in patients taking AIDS medications. That, in theory, should have rolled back the clock for the patient, restoring effectiveness to the older drugs -- and giving a new lease on life for an important subset of patients.

Instead, 22 out of 138 subjects who took time off from their AIDS medications had their disease worsen, compared with just 12 of 132 patients who continued taking their AIDS drugs. To assure a valid comparison, the patients in the second group also switched to a new mix of medications at the same time that the drug holiday group started taking a new drug cocktail.

Unfortunately, the percentage of patients infected with HIV that is resistant to current AIDS drugs is rising.

Two years ago, UCSF researchers forecast that 42 percent of those infected with HIV in San Francisco will have developed resistance to existing AIDS drugs. Last summer another study found that the percentage of AIDS patients in the city resistant to more than one drug had risen to 13 percent from 2.5 percent between 1996 and 2000.

Virtually all of the participants in the latest study were infected with multidrug-resistant strains of HIV. Although there is evidence that the drug- resistant strains of HIV may be less dangerous than the natural "wild strain" of HIV that typically causes the initial infection, they are still deadly. A total of 16 patients -- eight who took the drug holiday and eight who did not - - have died since enrollment began in June 2000.

Lawrence noted that the patients in this study were closely monitored, perhaps masking just how dangerous the drug holidays might have been. "We were able to avoid deaths in the interruption group because we caught them in time, " she said. "People doing this on their own might not be so lucky."

The message from the study, she said, is that patients who already have multidrug-resistant strains of HIV are better off continuing their therapy -- even if they are losing ground to the disease -- than taking a drug holiday.

E-mail the writer at srussell@sfchronicle.com.

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