TORONTO - When it comes to developing a safe, effective vaccine to stem the global AIDS pandemic, researchers agree there is one component they can't do without -- volunteers willing to become human guinea pigs for testing the experimental serums.
Tens of thousands of participants will be needed for clinical trials of vaccines aimed at preventing HIV infection, yet one study has found lots of reasons why people might be wary of offering up their bodies to advance this particular cause of science.
That's likely even more the case since the field suffered a major setback last fall, when a promising vaccine developed by pharmaceutical giant Merck not only failed to work in what was known as the international STEP trial, but actually increased the risk of infection in some volunteers.
A group led by Peter Newman, a professor of social work at the University of Toronto, decided to interview a number of people who had volunteered for the Toronto portion of STEP, but decided not to take part after going through the initial enrolment process.
Their reasons, he said, should be a cautionary tale for researchers in any future vaccine-testing endeavours.
"Pretty much, they all had altruistic intentions, that's why they did this in the first place," Newman said of would-be volunteers in Toronto, most of them gay men. "They said they wanted to help find a cure or find something that would prevent this disease ... they had a friend who was ill or had died in the past and they wanted to do their part."
"That was really across the board. So it's the issue that even despite that and the fact that they came in and said, 'Hey I'll do whatever tests I need to do to see if I'm eligible,' they said, 'When push comes to shove, I really don't want to do this."'
In questionnaires and interviews, 13 decliners in Newman's study cited a number of reasons for pulling out, chief among them concerns about coming up positive on an HIV test (even if they weren't actually infected) due to antibodies produced in response to the vaccine.
Respondents saw all kinds of possible repercussions from such a false-positive result, he said. As one explained:
"This could change your life. We are not talking about getting little round spots on your hands or something. We are talking about showing up positive. How can you tell your doctor, your insurance company? Like, how do you deal with that? Because this has a huge stigma for people."
A couple of subjects who decided against enrolling in the trial had contacted private medical insurance providers and were told they would not be eligible for some coverage if they took part, he said.
Some worried that a false positive might hurt their ability to get life insurance; others feared being denied entry to the United States (non-citizens with HIV are inadmissible by law) to work or visit friends and family.
Still others were concerned about their relationships, Newman noted. "They said, 'How am I going to explain to my partner? How am I going to explain to some guy I might meet and really like, you know I'm positive but I'm not really?"'
His study, recently published in the journal Vaccine, found that fears about possible side-effects from taking an investigational vaccine, inadequate remuneration and committing several years to a particular trial also tipped the balance against participating.
Jose Sousa, chair of the community advisory committee for the Canadian HIV Trials Network, called the concerns raised by the Toronto respondents "pretty right on," and said they are surprisingly representative of the broader community of people at elevated risk for HIV and thus candidates for vaccine trials.
"The big thing is being antibody-positive afterwards and insurance," Sousa said from Montreal. "You don't know it's a false positive until it's double-checked and insurance (companies) don't do that."
Newman suggests future trials should be set up to provide more support for those people willing to roll up their sleeves for experimental inoculations, including free psychosocial counselling; an ombudsman to deal with insurers and other institutions; and reasonable payment for time, effort and risks involved with the research.
They are suggestions that scientists should not ignore, advised Sousa. "If they want their studies completed, they better listen to the community."
Addressing such concerns will be critical for future vaccine research, agreed Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise in New York, especially since the STEP trial results may have made potential volunteers gun-shy about coming forward.
"So if volunteers think the next trial is either not going to work or fail, then they're going to be increasingly resistant to volunteer for trials because they'll figure the scientists have lost their way and don't really know which way to go."
Yet Bernstein doesn't view the STEP trial as a failure -- as many have called it -- but a learning experience that will help researchers refine the next generation of test vaccines.
"I think the failure has been our expectation that one vaccine trial would be a home run, would give us a vaccine ... So I think we have to convey to the communities who are potential volunteers that this is a long, incremental journey and a learning journey -- and we need their help."
Dr. Rafick-Pierre Sekaly, a vaccine researcher at the University of Montreal, agreed that the STEP trial may mean some people will be leery of getting involved in subsequent research.
Yet, even with pre-testing in laboratory animals, scientists cannot foretell how a person's immune system will react to an inoculation, Sekaly said. "The primate model is not a predictor, the mouse model is absolutely by no means a predictor."
"The only way to know if a vaccine is going to work or not is by going into humans."
