Story by Christine Grillo
Behavior change may be our best hope for stemming the HIV/AIDS epidemic. Why is it so hard to evaluate the interventions?
In the late 1980s and early 1990s, investigators at the Medical College of Wisconsin wondered if popular men in gay bars could effectively promote safe-sex messages.They designed a randomized-controlled trial (RCT) that was conducted in three small Southern cities. In Biloxi, Mississippi, where the intervention took place, the popular men were recruited to endorse condom use to bar patrons. The two comparison cities received no specific intervention and served as controls.The results were impressive. In Biloxi, the number of risky sexual encounters fell by about 30 percent over two months. In the other two cities, the risky behavior stayed the same. Another trial, this time in 16 cities, yielded the same results. A new, effective HIV/AIDS intervention had been identified.
Ten years later, epidemiologist David Celentano, a veteran in the field of HIV/AIDS prevention and of RCT design, did a similar trial with the same intervention in five countries on four continents. Over 24 months, the number of risky sexual acts decreased by 33 percent in the intervention group. But the number of risky sexual acts decreased by the same amount in the comparison group. Clearly, risk had been reduced all around, but there were no differences between the two study arms. (With dramatic downward shifts in risk in all five countries, it seemed unlikely that anything other than the trial itself had effected the risk reduction.) The results surprised Celentano. Because the intervention known to work seemed no more efficacious in the trial, it might be cast aside.
The standards for ethical conduct of trials had changed, says Celentano, the Charles Armstrong Chair in Epidemiology at the Bloomberg School. In the intervening years, many new interventions had been proven effective, and ethical obligations required that they be offered to the control arm of the later trial. Celentano lists the services offered to participants: educational materials, free condoms, HIV and STI testing and treatment, pre- and post-test counseling, and extensive interviews about risk behavior. "And that's just the control group," he says.
The stakes for finding effective HIV preventions are high: An estimated 33 million people live with HIV, another 2.6 million are newly infected every year and 1.8 million die of AIDS annually. Now 30 years old, the field of HIV/AIDS prevention draws scores of researchers who spend billions of dollars in a race to find ways to prevent transmission. Some want to identify biomedical interventions, such as microbicides, vaccines and male circumcision. Others are counting on behavior change programs—safe sex education, peer counseling, media campaigns— to slow down the epidemic.
But the field of behavior change, in particular, is tricky terrain for evaluation. As new interventions are shown to be effective, ethical obligations and aspirations evolve, making evaluations more challenging. And as real-world HIV/AIDS conditions become more complex, RCTs begin to seem less feasible.
In HIV prevention trials, investigators compare the incidence of new infections among the control arm to those among the intervention arm. For an intervention to be deemed effective, the intervention arm must show significantly fewer infections than the control, which reveals the intervention's impact. "No researcher wants people to get infected," says Maria Merritt, a core faculty member in the Johns Hopkins Berman Institute of Bioethics, "but the expectation is that some participants will get infected."
Researchers and ethicists agree: Investigators have an obligation to minimize risk to all participants. And in this field, there is an acceptable level of protection for all participants in a trial that has been generally agreed upon by experts.This standard of prevention guides what is offered to participants—known as "the prevention package"—in order to minimize risk. (Prevention packages often include counseling, testing and treatment, like the suite of services offered in Celentano's trial.) But, notes Merritt, PhD, an assistant professor in International Health, some people would add that there is an obligation to maximize benefits for participants.This might take the form of making available as many known effective interventions as possible to all participants.
Not surprisingly, robust prevention packages tend to dilute the results of a trial. Overall, there may be fewer participants with new HIV infections, which is a wonderful thing. "The paradox," says Jeremy Sugarman, deputy director for medicine at the Berman Institute, "is that the more effective the basic package, the less likely that the research question will be answered."
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