Global HIV vaccine trials face ethical challenges

Enrollment in AIDS-stricken countries faces scrutiny

HIV vaccine trials likely will continue for a decade or longer, raising questions about ethical considerations of enrolling participants across the globe.

Since none of the studies so far have found a vaccine candidate that prevents HIV infection, one of the biggest ethical concerns is promoting inflated hope among trial subjects.

"There is the concern that despite having been told that this is research and the vaccine may not succeed in preventing HIV infection, participants will engage in risky behavior in the hope or belief that the vaccine will work," says Ruth Macklin, PhD, a member of the HIV Vaccine Advisory Committee at the World Health Organization, and a professor of Biomedical Ethics in the department of epidemiology and population health at Albert Einstein College of Medicine in the Bronx, New York.

"Evidence indicates, however, that participants in the trials have not actually engaged in 'behavioral disinhibition' — that is, engaging in behavior that is any more risky than when they are not in a trial," Macklin notes.

One reason HIV vaccine research is more ethically challenging is because HIV remains a stigmatizing condition, Macklin says.

"Phase III trials are almost always conducted on populations at high risk of becoming infected," she says. "Even though the participants are not infected when they enroll, if it becomes known that they are in a preventive vaccine trial, they might therefore be stigmatized."

The stigma factor isn't an issue for other types of vaccine trials, Macklin says.

There also has been the ethical challenge of pursuing the vaccine in the areas that need it most.

The HIV virus is different in various regions of the world, and any vaccine that is developed will need to be created specifically for the dominant virus present in the area where it will be given.

The challenge has been in starting vaccine trials in the resource-poor areas hardest hit by the pandemic, says Pat Fast, MD, PhD, executive director of medical affairs for the International AIDS Vaccine Initiative (IAVI) of New York.

"There wasn't enough emphasis being given to people who needed the vaccine the most, including the people in Africa and Asia," Fast says. "Less developed countries have fewer ways to protect themselves against HIV."

So organizations such as IAVI and the Bill and Melinda Gates Foundation have provided the funding and infrastructure necessary to initiate vaccine research in resource-poor countries.

HIV vaccine research is very expensive, and it requires collaboration, Fast says.

For instance, the IAVI shares information with the U.S. Military HIV Vaccine Research Program and the Medical Research Council in the United Kingdom. The organization also receives Gates Foundation funding, as well as money from the United States and European governments, she adds.

"You have to go into these countries and spend time and make sure people have a sustainable operation that's not just dependent on one trial," Fast says. "You don't want to go in and set up the trial, and then when you leave and people go away, the facilities fall apart."

The goal is a long-term effort so that when the AIDS vaccine finally is discovered, the existing infrastructure can be used for other health care and research projects, she adds.

An ethical challenge related to HIV vaccine work is that the vaccine is likely to make participants test positive for HIV even when they are not really infected, Macklin says.

"If participants are in a setting where there is mandatory testing, such as in the military, it must be made clear to the testing authorities that although the participants have antibodies, they are not infected," Macklin says. "This is usually handled by providing a card to each participant, affirming that they are enrolled in HIV vaccine research."

Another ethical concern has involved worries that researchers might not counsel vaccine participants fully about practicing safe sex because of their desire to see if the vaccine succeeds in preventing infection, Macklin says.

"That is, if no one engages in risky behavior, there is no chance that anyone will be exposed to HIV and, therefore, no way of knowing whether the vaccine is efficacious," Macklin says. "However, there is no evidence that researchers are failing to counsel vaccine trial participants appropriately."

Vaccine trial investigators even distribute free condoms to encourage participants to have the safest possible sex, Macklin says.

"Both the informed consent process and the counseling are designed not only to provide full information to participants, but also, the vaccine trials have employed a test of understanding before potential participants can be enrolled," Macklin says. "By this method, researchers try to ensure that participants fully understand that the vaccine may not work, that they may test positive even if not infected, and that they are well-informed about the best method to prevent becoming HIV infected."