VaxGen trial social and behavioral data

When a scientific trial ends with the experimental product proving to be ineffective, it is easy to say that the trial was a failure. This was one of the responses to the news that the world's first Phase III vaccine trial, which tested AIDSVAX®, showed no protection overall (for more on scientific data, see above). But this is not the whole story: at least some success can be measured in how a trial was conducted; how many volunteers remained through the end of the study; and how volunteers' behaviors and beliefs were affected by the trial. Here, the AIDSVAX® trial provided some good news, and some interesting lessons.

Before the trial began, many scientists doubted whether enough high-risk volunteers could be recruited at North American and European clinical study sites to establish a trial population, also called a cohort, with sufficiently high infection rates (incidence) and stability to meet the trial requirements. The trial followed volunteers for three years, and called for 7 immunizations.

But both the incidence and retention rates for the trial proved these fears unfounded. The trial enrolled over 5,100 men and 309 women. At the end of the 3 year study, VaxGen reported an incidence of 2.7% in men and 0.8% in women. The company also reported a retention rate of over 80%, a figure which is considered a success for a trial occurring over such an extended time period. These retention rates are particularly striking in the trial's high-risk women, most of whom live marginalized lives: the majority are poor, use drugs, exchange sex for shelter or money, and have unstable housing situations. During the study, many were also arrested and spent time in prisons and jails. Against this stark backdrop, the women and the trial site staff established durable, trusting relationships, reflected in the over 80% retention rates.

Another early concern was that trial participation would dramatically change volunteers' frequency of risk behavior. On the one hand, participants might assume that the vaccine is protective and therefore increase their risk behaviors. On the other hand, the risk reduction counseling that volunteers receive at each study visit might lead to greatly reduced rates of risk behaviors, which could lower HIV incidence to the point where it becomes impossible to get a scientifically reliable answer on the vaccine's ability to protect.

In the end, neither of these scenarios came to pass. Three years after enrolling in the trial, men and women reported rates of high-risk behavior that were at or just below those reported at the beginning of the trial.

These were overall data. There were other studies asking more specific questions, such as whether volunteers' beliefs about whether they received the vaccine or placebo affected risk behavior. The trial was blinded, meaning that neither volunteers nor staff actually knew who received the vaccine or the placebo. In spite of this, volunteers made assumptions about what they had received. Researchers at the U.S. Centers for Disease Control and Prevention (CDC) found that these assumptions changed rates of risk behavior.

The CDC team grouped volunteers by whether they believed they had received the vaccine, the placebo or had no fixed idea about what they received. For the men who have sex with men, volunteers who thought they had received the vaccine reported consistently higher rates of unprotected anal intercourse than men who believed they had received the placebo or did not know. In contrast, at the 12 and 24 month visits, women who thought they had received the placebo had higher rates of risk behavior than those who thought they were given vaccine.

So despite the trial's overall successes with recruitment and retention, there are areas for improvement in future studies. Even when trial staff repeatedly explained that the vaccine was experimental and might not provide any protection at all, some people still leapt to conclusions about being protected—without knowing whether they had received the vaccine or not. Data from the women volunteers (a group with less education than the men) suggests that there may have been some confusion around the terms "vaccine" and "placebo." Both findings highlight the need for clear, ongoing, audience-appropriate education and information for vaccine trial volunteers.