Some articles appearing in the Indian
media have raised questions about
the country's first AIDS vaccine trial, conducted
at the National AIDS Research
Institute (NARI) in Pune and supported
jointly by the International AIDS Vaccine
Initiative (IAVI) and the Government of
India through the Indian Council of
Medical Research and the National AIDS
Control Organisation. IAVI would like to
clear up any misperceptions and misunderstandings
that may have occurred
about the process by which experimental
vaccines are tested and the role India
plays in the global efforts to develop
an AIDS vaccine.
In February 2005, investigators at NARI,
Pune began the Indian portion of a trial
of an AIDS vaccine candidate called
tgAAC09. These tests were part of a
Phase I trial of tgAAC09 that was
also being conducted in Belgium
and Germany.
Like all Phase I trials, this one was designed
to test primarily whether the vaccine candidate
was safe and well-tolerated in
humans. The vaccine candidate did indeed
prove to be safe and well-tolerated.
Investigators in the Phase I trial of
tgAAC09 also collected preliminary immunogenicity
data, information about whether the immune systems of the trial
volunteers responded to the vaccine, as
indicated by certain markers in their
blood. Immunogenicity (inducing an
immune response) is an indication that
the vaccine candidate might warrant
eventual testing to see if it can protect
against HIV infection or development of
AIDS. The primary purpose of collecting
immunogenicity data in a Phase I trial is
not to determine whether the immune
responses are strong enough; that is
tested in a Phase II trial or trials by trying
several doses or schedules for immunisation.
Rather, the purpose of collecting
immunogenicity data in a Phase I
trial is to help determine what the proper
dose and schedule might be for further
testing of the vaccine candidate.
Because the Belgian and German portions
of the Phase I trial of tgAAC09 began
first, preliminary immunogenicity data
from those arms of the trial became available
soon after the start of the Indian
portion of the trial. The preliminary data
from the subset of volunteers in Europe
who received just one dose of the vaccine
suggested that the candidate was
only
modestly immunogenic; three different
dosage levels had been administered
and even at the highest doses, few of
the
volunteers in Europe registered an
immune response. After the European
data became known, to ensure transparency,
all prospective trial volunteers in
India were fully informed about the
European data as part of the informed
consent process. Volunteers who were
already enrolled in the trial in India were
given the new information and reminded
of their option to withdraw from the
trial at any time.
Some commentators have suggested that
the modest size of the immune responses
in the preliminary results from Europe was
reason to discontinue the Indian arm of
the trial. It has even been written that
the Indian portion of the trial continued
though it was known within weeks of its
start that the vaccine candidate had
"failed" in tests in Europe.
In fact, the candidate did not fail in tests
in Europe. At that time, the candidate was
in Phase I testing, for safety and tolerability,
and the preliminary data from
Europe showed it was performing well
on those measures. It's true the preliminary
data collected in Europe indicated
the candidate was modestly immunogenic,
but that information was collected
not to determine whether tgAAC09 had
'passed' or 'failed' an immunogenicity
test – that's for Phase II – but rather to
help investigators determine how much
of the candidate to administer in the next
phase of testing.
The data gathered in the three-country
Phase I trial of tgAAC09 did just that.
When data from all arms of the trial were
collected and analysed, researchers were
