JOHANNESBURG, 22 October 2009 (PlusNews) - The recent news that
for the first time an HIV vaccine had shown some protective
effect generated widespread excitement, until it emerged that the
results were based on the most promising of three different
analyses of the trial findings.
The trial team in Bangkok, Thailand's capital, announced on 24
September that a combination of two vaccines had reduced the rate
of HIV infection by 31 percent in about 8,200 volunteers,
compared to around the same number who were given a placebo.
A few weeks later, researchers who had seen full data from the
trial told Science magazine that an analysis based only on
participants who had received all six doses of the vaccine at the
right times did not show a statistically significant protective
It was hoped that the release of more details from the trial to
coincide with the AIDS Vaccine 2009 conference taking place in
Paris this week would settle the question of whether the vaccine
results were really as significant as the initial announcement
had suggested or a mere fluke. Instead, full results of the
study, published online yesterday in the New England Journal of
Medicine (NEJM) raised more questions than they answered.
The 31 percent efficacy in the initial announcement was based on
a "modified intention-to-treat" analysis that included all the
16,402 trial participants, except for seven who were found to
have contracted HIV before receiving any vaccinations.
A second analysis included those seven, while a third
"per-protocol" analysis involving 12,452 participants - the one
cited in Science magazine - found that the vaccine was only 26
percent effective. This was not enough to be statistically
significant, meaning that the difference between the vaccine and
the placebo arms of the trial was so small that it could have
been a coincidence.
Dr Jerome Kim of the US Military HIV Research Programme, who
helped lead the trial, yesterday told reporters at the vaccine
conference in Paris that the modified intention-to-treat analysis
was the most accurate, but others disagreed.
A statistician quoted in a New York Times report placed more
emphasis on the analysis that included the seven HIV-positive
participants, while another did not believe that any of the
analyses provided sufficient evidence the vaccine worked.
In an editorial accompanying the article, NEJM editor Raphael
Dolin said that "although the merits of each type of analysis can
be debated, all three yielded a possible, albeit modest, effect
of the vaccine in preventing HIV infection."
The study authors also argued that, taken together, the three
different analyses of the results were "consistent with a modest
protective effect of vaccine", but could not explain why other
findings from the trial indicated that the vaccine's efficacy
appeared to decrease over time, or why it was less effective
among participants at high risk of infection.
They were also unsure whether it was one of the two vaccines that
produced a potentially protective effect, or the combination of
the two. Dolin noted that the findings raised "a number of
questions that have important implications for future directions
in vaccine research", and recommended that the duration of the
vaccine's effect be addressed by following up the trial
participants, as well as by future trials.
According to a report by a South African news service, Health-e,
Colonel Nelson Michael of the US Military HIV Research Programme,
another lead investigator of the Thai trial, told a press
conference in Paris that a further study of the vaccine may be
conducted in South Africa, which has a much higher HIV prevalence
than Thailand. The vaccine would have to be modified to contain
the strain of HIV most common in sub-Saharan Africa.
See also: GLOBAL: First positive results from an HIV vaccine