IAVI statement on new analysis of STEP large-scale AIDS vaccine trial

The International AIDS Vaccine Initiative (IAVI) issued the following statement from its President and CEO, Dr. Seth Berkley, following the release of the first analysis of the entire study population from a late-stage AIDS vaccine trial, known as the STEP study. The analysis confirmed an earlier analysis of data on half of the 3,000 trial volunteers, released Sept. 21, that concluded the vaccine candidate, manufactured by Merck & Co., was not efficacious.

The Merck candidate neither prevented HIV infection nor lessened the amount of virus in those who became infected. According to the trial co-sponsors, Merck and the HIV Vaccines Trial Network (HVTN), the new analysis suggests that those who received the vaccine, which cannot cause HIV infection, might have an increased susceptibility to acquiring HIV. Volunteers who had prior natural exposure to the Ad5 vector that was used in the vaccine might be particularly susceptible, the trial sponsors said. Responding to the news, which was announced at a special open scientific session at a meeting of the HVTN in Seattle Nov. 7, IAVI’s Dr. Berkley said:

“It’s disappointing that the Merck candidate didn’t work, but it’s important to bear in mind that this was one trial, of one candidate. It is as vital as ever to find an AIDS vaccine, and the effort will continue.

“It took 47 years after the polio virus was discovered before a vaccine was developed. Chicken pox took 42 years. Rotavirus, which causes diarrheal disease, took 33. HIV was discovered 24 years ago and we’ve only had a serious AIDS vaccine effort for about a decade, with only two candidates tested for efficacy. History tells us it takes a long time to develop a vaccine, but it also tells us it’s the only way to eliminate a plague like AIDS. No viral epidemic has been defeated without a vaccine.

“It’s also vital that everybody keeps straight what we know and what we don’t know. We know the Merck vaccine didn’t work. We don’t know why. We know that more people who got the Merck candidate than got the placebo wound up becoming HIV infected. We don’t know if that had anything to do with the candidate or not. Given that the trend didn’t rise to statistical significance, it could have been chance. And if the vaccine was a factor, we don’t know why.

“Our view is that the results of the Merck trial will require a great deal more study before larger lessons can be drawn from them for the larger AIDS vaccine field.

“In the meantime, the news should be absorbed with some perspective. The world owes a debt of gratitude to the STEP trial’s sponsors and, most of all, to the study volunteers. Though the Merck candidate failed, the trial did not. The contribution of the volunteers was not in vain. As a result of their dedication, the field will have new data that will inform future vaccine design, help with the prioritization of candidates in the pipeline and guide decisions on how to best proceed with ongoing and upcoming trials.

“It is also important to recognize that the failure of the Merck product to prevent HIV infection is not unexpected. Merck’s candidate, like nearly all vaccine candidates now in the pipeline, was designed to activate the T-cell arm of the immune system. T-cells work like commando units, travelling through the body, seeking out pathogen-infected cells, which they then kill. Because T-cells only attack cells that are already infected, many scientists, including those at IAVI, think T-cell vaccines are unlikely to protect individuals from becoming infected. It’s more likely T-cell vaccines will reduce the amount of virus in people who, once vaccinated, become infected. In the event, the Merck vaccine did not achieve either result.

“Because of this limitation of T-cell vaccines, some scientists in the field, including those at IAVI, in recent years have shifted more resources toward discovery of next-generation candidates, including those that would activate the antibody arm of the immune system. Antibodies act like the body’s border guards, stopping pathogens from entering the body, and thus preventing infection.

“Whatever lessons the STEP trial eventually teaches us, one thing is certain: the need for a vaccine has never been greater. The arithmetic hasn’t changed. About 39 million people are HIV infected; three million die annually of AIDS. Antiretroviral therapies prolong the lives of those who become infected, but for every person who is put on ARV treatment, there are six new HIV infections. UNAIDS recently estimated that to fulfil the G8’s goal of providing a comprehensive AIDS response, including prevention, treatment and care, to everyone in the developing world who needs it would cost at least $45 billion a year by 2015, more than five times what is being spent today. Spending on AIDS would have to go from a tenth of all overseas development to a third, jeopardizing other development goals. And although ARVs ease the suffering of those who are sick, they will not end the epidemic. Only a vaccine holds out the hope of eliminating AIDS.

“And there are sound scientific reasons to believe we can develop a vaccine against AIDS. The human immune system, it turns out, is better at fighting HIV than we’d originally thought. Most people suppress the virus for many years before developing AIDS. A small number never contract the virus despite repeated exposure. Others are infected but have not developed AIDS. What’s more, vaccine studies in non-human primates, our closest relatives, show that infection can be prevented entirely. With such strong evidence in humans and in animals, scientists think a vaccine is possible.

“Developing a truly effective, preventive vaccine has been, and will continue to be, an extremely challenging scientific goal. But given the human stakes, we have no choice but to redouble our efforts to realize that goal.