CROI 2013: The VOICE Results—A Social Scientist’s Perspective
As we learned on March 4 at the 20th Conference on Retroviruses and Opportunistic Infections, researchers with the VOICE trial saw no HIV-prevention effect of daily oral PrEP or a vaginal microbicide among women in Uganda, South Africa, and Zimbabwe—a finding that is being chalked up to lack of adherence to the study products.
Adherence was estimated to be high, but data from blood samples told a very different story: Of the 773 women whose blood was sampled quarterly to examine drug levels, 50% to 58% had no detectable tenofovir or Truvada in their blood at any study visit. “The bottom line is the women were not using the products,” said protocol co-chair Jeanne Marrazzo in a press conference.
See “VOICE Trial Results on Daily HIV Prevention for Women” for the full story on this PrEP/microbicide study.
To social scientist Judith D. Auerbach, PhD, a consultant to the NIH Office of AIDS Research and San Francisco AIDS Foundation, the VOICE results raise a number of questions—but not the ones you might think. In this Q&A, Dr. Auerbach offers her take on the VOICE trial and why biomedical research has a lot to learn from the contexts in which people use (or don’t use) study products and avoid or acquire HIV.
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BETA: As a social scientist, what are your thoughts on the results we heard on Monday from the VOICE trial?
Dr. Judith D. Auerbach: What I find most interesting is how the field talks about what went on in this trial and what the problems or issues are. We heard that women in the trial who said they were taking the oral drug (although the gel was also problematic) were not actually taking the pill, so the issue becomes cast as an adherence problem: Women didn’t take the drug as prescribed.
The other way people talk about the trial is to say that the product didn’t work, or the trial didn’t work. And neither of those is true. What we know is that the product works, in an efficacy sense, when it’s in the body—you know, “the right drug, at the right dose, in the right place, at the right time.” Although we don’t have really solid data yet around tenofovir in women, as we do for gay men, it’s still pretty compelling that, biologically, if the drug is in the body it’s going to work.
So the issue is not that the drug doesn’t work, and the issue isn’t even that the trial didn’t work—because the trial did everything it was designed to do. The issue is really that certain women don’t take drugs, period.
BETA: So for those particular women, no amount of adherence counseling is likely to increase the use of a daily oral pill? It’s just not the right fit for them?
Dr. Auerbach: Right. When you look at what kind of contraception the women at these trial sites use, it’s primarily injectable hormonal contraceptives, not oral pills. I look at that and ask, “Well, if you knew that women in these communities typically do not take oral contraception, what made you think they’d take an oral pre-exposure prophylaxis pill?”
BETA: What are the implications, then, for the design of future clinical studies of HIV prevention tools?
Dr. Auerbach: Going into these trials of women-controlled HIV prevention, we need a better understanding of who these women are and what their lives are all about, and also how the trial itself becomes an intervention in a community—how it engages community participants but also changes the community, and how community members change it.
One of the interesting conversations going on around the VOICE results is about the incentives for women to participate in these clinical trials. There is a legal requirement in South Africa to provide a certain level of financial incentive for participating this type of biomedical research, and it has become, in most people’s estimation, an inducement to participate.
A lot of folks in really resource-limited settings might quite sensibly say, “Well, I could get money for participating in this trial, and I’d get a lot of health benefits—monitoring of my health and wellness, good counseling, access to condoms—so it’s a good deal. I have no intention of taking the pill, but I’m not going to say that.”
So there’s an important conversation happening about the ways in which the financial incentives that are provided—for good, ethical reasons—have in fact begun to corrupt what goes on in the trial. Again, it raises the question of how much anybody’s really investigating the trial itself as an apparatus that affects people who participate in it, and how participants interact with the trial—not just with the drug, but the trial itself.
BETA: I recently heard it said regarding PrEP that “adherence is a behavior.” Doesn’t that speak to the importance of considering the contexts in which biomedical interventions are used—or not used?
Dr. Auerbach: Absolutely! Jeanne Marrazzo did a fabulous job presenting the VOICE trial results again at the AVAC community meeting Monday night, and afterward she said that one thing she learned from VOICE is that a biomedical intervention trial is really a behavioral trial, too.
That’s the kind of thing people in the behavioral and social sciences have been saying for 30 years! Is it only when MDs say it that it becomes recognized as an important reality? There are a lot of interesting questions around the social and behavioral factors at play in these HIV prevention trials, and there’s not sufficient social science research on any of them. I think unless and until that kind of research happens, we’re going to keep running into the same problems.
In these clinical trials, researchers try to control out all the “noise”: You want similar women in similar circumstances so you can tease out the product effect. But social scientists say that the differences about women and their context—their community, their lives, their choices, their psychology, their culture, their age, all that stuff you’re trying to control for—are exactly what’s really important in these trials because they enter into how individuals think and (what they say) about taking a product.
There have been improvements in the formative research for these trials, and in understanding the whole question of adherence—why people do or do not take the products being tested in these studies—but they often can’t see the forest for the trees. And the forest is really where the action is!
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Reilly O’Neal is the editor of BETA.