An experimental HIV vaccine cuts infections by a third, newspapers reported. The Guardian called it a “breakthrough”, and the first evidence of a possible vaccine against AIDS. It said a trial in more than 16,000 men in Thailand found vaccinated men had a 31% lower risk of infection.
The news reports are based on an announcement by the US Military HIV Research Program and the Thai Ministry of Public Health. The full reports of the science behind this announcement have not been published yet, so it is not possible to report on specific details.
This result has been greeted with varying degrees of optimism by scientists and organisations involved in HIV vaccine research. Many advise caution in that the effect was modest and that it is “early days”. It is also not yet known whether the findings apply to strains of HIV that are common outside Thailand.
The researchers say they have already “learned a great deal from this study, particularly in terms of conducting large-scale HIV prevention trials, and will continue to learn more as additional research is conducted”.
What is the basis for these current reports?
The news reports are based on results from a large trial in Thailand that have yet to be published in full.
The Phase III HIV Vaccine Trial was designed to test the vaccine’s ability to prevent HIV infection, as well as its ability to reduce the amount of HIV in the blood of people who were infected over the course of the trial.
The vaccine under study is a combination of two immunogens (substances that provoke an immune response) that were developed using different techniques. The first (ALVAC-HIV) contained a dose of a canarypox virus, known as vCP1521, that researchers had engineered to contain HIV genes. This was followed by a dose of AIDSVAX B/E, using the gp120 proteins that are common on the surface of the HIV virus.
The theory was that the two vaccines would work together through a mechanism called prime boost, where the same antigen (in this case HIV) is given in two different ways successively. Exposure to the first dose (ALVAC-HIV) primes the immune response, which is then followed by the AIDSVAX B/E vaccine which boosts the response.
The study caused some controversy when it began. This is because neither of the two vaccines used for this trial had demonstrated individually that they could induce immune responses that would be adequate enough to protect people from HIV infection.
At the time, a group of prominent researchers published a letter in the journal Science voicing their concerns, saying, “There are no persuasive data to suggest that the combination of ALVAC and gp120 could induce better” immune response “than either component can alone”. They said that while the question of prevention of HIV is fundamentally worth addressing, they had doubts as to whether either of the constituents of the proposed vaccine “have any prospect of stimulating immune responses anywhere near adequate for these purposes”.
In their letter, this group of researchers highlighted a decision to cancel a similar trial that had been planned in the US. They questioned the scientific reasons behind a different decision for the Thai trial. Additionally, questions were raised over the cost of the trial at over US$119 million.
Who carried out the trial?
The trial was conducted by the Thai Ministry of Public Health in collaboration with a team of Thai and US researchers and coordinated by the US Military HIV Research Program (MHRP).
It was funded by the US government and the Thai Ministry of Public Health. The pharmaceutical companies that made the vaccines provided support.
The MHRP states that the trial was in Thailand because it had a severe, generalised HIV epidemic and because it was one of the first countries to have developed a National AIDS Plan and a National HIV Vaccine Development Plan.
What did the trial involve?
The trial was conducted at 47 health centres in the Rayong and Chon Buri provinces of Thailand and eight clinical sites.
More than 16,000 volunteers were randomly selected to receive either the vaccine combination or a placebo drug. Volunteers were HIV negative 18-30 year old males who were at average risk of HIV infection.
Vaccinations ended in July 2006, and volunteers received an HIV test every six months for three years. They were also counselled on how to prevent becoming infected with HIV from the beginning of the trial and every six months for a total of three and a half years. Volunteers who were infected with HIV during the trial were given free access to HIV care and treatment, and were offered follow-up in a separate study.
It is not yet clear what the precise dosing schedules of the vaccinations were. This and other details should be available when more detailed information is published in October.
What are the reported findings from the trial?
Of the 8,197 men who were vaccinated, 51 were infected with HIV after the trial began compared with 74 new infections in the 8,198 men receiving a placebo. The difference of 23 infections translates to a 31% lower risk of infection in the vaccinated men.
The findings from this vaccine trial have been welcomed by researchers and organisations involved in vaccine research and undoubtedly by HIV patients too. Critics and supporters of the trial are reported to have been just as surprised by the findings.
Importantly, a detailed data analysis of the study’s results is currently underway and a formal report is being written. The peer review and scrutiny process that accompanies such a process will be important to highlight any potential problems with the trial.
The differences in infection rate between the groups are modest and a further in-depth data analysis by researchers is underway.
Most experts in the field appear to be cautiously optimistic about these findings, and say that it is “early days yet”, but the results appear to show there is potential for an effective vaccine for HIV. Commentators say the research is promising and especially welcome for AIDS researchers after 25 years of searching for a vaccine.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Science, 24 September 2009
The Guardian, 24 September 2009
The Times, 24 September 2009
BBC News, 24 September 2009
Links to the science
Press release and fact sheet