After taunting researchers for 30 years, HIV, the virus that causes AIDS, has relented a bit – at least that’s how many infectious disease experts are now interpreting results from two vaccine trials.
The first trial was a huge disappointment. The experimental vaccine, developed by U.S. drugmaker Merck, failed to prevent HIV infections so miserably, Merck halted the trial in September 2007. Two years later, results from the second trial were more promising. The trial was conducted in Thailand, involved more than 16,000 volunteers and used a combination of two vaccines. But three months after the results were released, questions persist whether the modest preventative effect of the Thai vaccine combo was real or due to chance.
Dr. Myron Cohen, a leading HIV/AIDS expert at the University of North Carolina, considers the results from the Thai vaccine trial “the first glimmer of hope” that there is a way to stop the spread of HIV/AIDS, particularly in poor countries.
Cohen, who also serves in a senior leadership position at the National Institutes of Health Center for HIV/AIDS Vaccine Immunology, also known as CHAVI, was one of two speakers Thursday at the N.C. Biotechnology Center in Research Triangle Park. The Triangle Global Health Consortium invited him and Kenneth Schulz, head of the biostatistics division at Family Health International in Durham, to give their takes on the Thai trial.
“Diseases come and go,” said Cohen. “There must be an end to the AIDS/HIV epidemic.” But he and Schulz agreed the Thai trial has yet to provide clues how to get there.
The failure of the Merck trial was such a great disappointment, because at the time the Merck vaccine was considered the best shot at preventing an HIV infection. It was designed to stimulate the production of white blood cells, or T-cells, and train them to attack and kill the AIDS virus once it entered the bloodstream. Researchers had invested much hope in the killer T-cell approach. Efforts to come up with a vaccine that stimulates neutralizing antibodies – an approach used in flu, polio and measles vaccines - had gone nowhere because of HIV’s ability to rapidly adapt.
The Thai trial appears to redirect researchers’ attention to the antibody approach, Cohen said. The vaccine combo was designed to first alert killer T-cells and then boost the antibody response. Volunteers who received the combo shots had about a 31 percent lower HIV infection rate than volunteers who received dummy shots. But the trial, which lasted three years and cost $105 million, doesn’t answer why.
Indeed, the Thai trial combined immune response boosters that either didn’t work in previous trials or had not been tested alone.
So, do the Thai trial results matter, and how? Cohen said he might find answers as he evaluates blood samples from the trial, which will take about a year. But for now, nobody knows.
His concerns echo an assessment another AIDS vaccine expert made of the puzzling results two months ago at the AIDS Vaccine 2009 conference in Paris.
“It’s a sign of our own ignorance of what’s really going on scientifically and biologically and, therefore, the need to think deeply of how to go forward,” Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise in New York, said during a presentation at the conference.
There’s no doubt, research will continue to look for an HIV/AIDS vaccine that is safe and works. As a matter of fact, several are being tested now and researchers are looking into repeating the Thai trial in Africa.
More than 33 million people worldwide are HIV positive, including an estimated 1.2 million in the U.S., according to 2008 figures of the World Health Organization and UNAIDS, the United Nations Program on HIV/AIDS. Every day, more than 7,000 people worldwide are newly infected with HIV and about 5,500 die from AIDS.
About two dozen antiviral medicines are available to suppress HIV, but treatment to keep the virus in check is expensive and carries the risk of side effects. Without a cure, a vaccine that prevents HIV infection appears to be the best chance to stop HIV/AIDS in its tracks.
So what should HIV/AIDS vaccine researcher focus on next? The response to this question will not only determine key scientific opportunities but also where money for research goes, Bernstein said. For example, funding for two key initiative, CHAVI and the Collaboration for AIDS Vaccine Discovery, or CAVD, is up for renewal.
In 2006, CHAVI and CAVD received a total of more than $500 million from the NIH and the Bill and Melinda Gates Foundation over five years. UNC and Duke University play leading roles in both organizations.