The tested vaccine regime was 31 percent effective in preventing HIV infection in the trial, which involved more than 16,000 adult volunteers, and was led by the Thai Ministry of Public Health and sponsored by the U.S. Army.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which provided additional funding and support for the study, called it an “important step forward in HIV vaccine research” in a statement, but emphasized “additional research is needed to better understand how this vaccine regimen reduced the risk of HIV infection.”
The results are a major boost for the HIV vaccine field, which suffered a crushing blow in late 2007 with the failure of a promising Merck vaccine that actually raised the risk of HIV infection for some participants.
After the Merck trial was shut down, many in the field felt they were at a dead end, said Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise
“I think the field went into a funk, a feeling that we really don’t know what direction to go,” said Bernstein, who was happily surprised by the positive results of the Thai trial.
“My heart skipped a beat,” he said. “This is really a landmark day, a momentous day, not just for the field, but for the planet.”
The protection provided by the vaccine is far too low for distribution, said Bernstein, so the trial was not a home run, but as the results are analyzed it should provide the field cues as to where to focus efforts next.
“No one could have predicted accurately the results that we heard about today,” said Bernstein, “So it’s a demonstration that we have a lot to learn still about how we protect ourselves from HIV.”
Particularly surprising to researchers and experts was how the vaccine prevented infections, but didn’t reduce viral load.
The assumption, said Rowena Johnston, vice president of research for the Foundation for AIDS Research, known as amfAR, has always been that it would be easier to develop a vaccine that had a therapeutic effect, but the shot failed to reduce the amount of virus in the blood of subjects who became infected. Researchers had hoped that if the vaccine didn’t prevent infections, it would at least cut the virus to levels so low it couldn’t be transmitted.
“It seemed like a lower bar to modify infection after it occurs as opposed to actually preventing infection in the first place,” said Johnston, but the trial results suggest the opposite.
Johnston said that when the blood samples are analyzed further, researchers will be able to compare the immune response of a vaccinated individual who still became infected to the response in a vaccinated individual who was protected, providing a sign post for future research that has never been available before.
The Thai Phase III HIV vaccine study opened in October 2003 and tested a two-vaccine combination in a “prime-boost” approach, in which the first one primes the immune system to attack HIV and the second one strengthens the response.
Neither vaccine used in the study stopped HIV infection when tested alone in previous trials, raising some questions about if the combined trial should be done.
The first vaccine, ALVAC, from the French drug maker Sanofi Pasteur uses an altered bird virus to carry synthetic version of three HIV genes into the body.
The second, AIDSVAX, is licensed by Global Solutions for Infectious Diseases, a nonprofit founded by some former employees of VaxGen, which originally developed the vaccine, and contains a genetically engineered version of a protein on HIV’s surface. Neither can cause an HIV infection in a human, said Bernstein.
“The reason for that is that the vaccine used individual components of the virus that we know are not AIDS causing,” he said.
Participants were counseled on how to avoid becoming infected with HIV and were tested for HIV infection every 6 months for 3 years.
In the final analysis, 74 of 8,198 placebo recipients became infected with HIV compared with 51 of 8,197 participants who received the vaccine regimen. This level of prevention, 31 percent, is considered statistically significant.
A vaccine would normally need at least an 80 percent level of prevention to be licensed, said Johnston, but if an HIV vaccine with that level of protection can eventually be developed, she said it would “make a meaningful difference in millions of people’s lives.”