Zealous Adherence: Erratic HIV therapy hasn’t fueled resistance

Among people infected with HIV, those who don’t consistently take their antiretroviral drugs as prescribed are no more likely to develop drug-resistant HIV than are patients who adhere to their treatment schedule, researchers report. This result contradicts a widely held assumption among health professionals that irregular use of HIV therapy has been a factor in spreading drug-resistant strains of HIV, says David R. Bangsberg of San Francisco General Hospital.

The assumption arose in part because poor adherence to drug regimens, particularly among indigent and homeless populations and illegal-drug users, has contributed to epidemics of drug-resistant tuberculosis, Bangsberg says. A similar situation for HIV treatment would create an ethical dilemma, he notes, because giving HIV drugs to people who are likely to take them sporadically might increase disease risk for the rest of the population.

To assess the relationship between treatment adherence and drug resistance, Bangsberg and his colleagues followed 148 impoverished, HIV-infected residents of San Francisco who lacked permanent housing or received government-provided meals. The researchers measured adherence by seeking out the volunteers without warning and comparing the number of pills they had at hand to the number they should have had if they were complying with their prescriptions. The scientists also took monthly blood samples over 6 months of treatment to monitor the volunteers’ concentrations of HIV and to determine how many drug-resistant mutations the virus had developed.

Many people who took their pills consistently had no detectable blood concentrations of HIV and therefore no apparent drug-resistant mutations.

Among the minority of good adherers who did have detectable viral loads, however, drug-resistant mutations of the virus were more common than they were in poor adherers, Bangsberg and his colleagues found. Over a 6-month period, 23 percent of the drug-resistant mutations arose in the one-fifth of volunteers who took their medication most consistently; only 12 percent of the mutations cropped up in the one-fifth of the volunteers who complied least consistently with their prescriptions, the researchers report in the Sept. 5 AIDS. As a group, therefore, good adherers contribute at least as much to the rise of drug-resistant HIV as poor adherers do.

The finding “in no way suggests that patients should take less of their drugs,” Bangsberg says. Taking antiretroviral drugs religiously is the best way to keep viral loads low and to stave off the onset of AIDS, he adds.

“There’s probably an over-exaggerated risk of resistance in [poor and drug-abusing] populations,” comments Gerald H. Friedland, a Yale University researcher who studies adherence to HIV-drug regimens. Because fear that drug-resistant HIV arises most rapidly in those populations is apparently misplaced, “we shouldn’t exclude patients [from therapy] who are thought to be nonadherent,” he says. “The patient might do harm to himself or herself by not taking the drugs . . . but they wouldn’t add to the total cumulative pool of resistant virus.”


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