February 27, 2008
Dear Advocates,
This update contains links to and context for newly-released
information about the STEP and Phambili vaccine trials, along with information
on an upcoming open meeting at the National Institutes of Health (NIH) on on
priorities and directions for AIDS vaccine research.
Hosted by the NIH, the March 25th "Summit on HIV
Vaccine Research and Development" will include a discussion of priorities and
resource allocation for the NIH vaccine program. Registration is now open. Click here
for more details. AVAC will be attending the summit and will circulate a
report via the Advocates' Network shortly afterward.
Useful tool for
understanding STEP data to date
The Vaccine Research Program at the NIH National Institute
of Allergy and Infectious Disease (NIAID) has developed an explanatory slide
set which provides clear summaries of the multivariate analysis of data from
the STEP trial of the Merck AIDS vaccine candidate, MRK-Ad5, as well as answers
to a handful of frequently asked questions related to STEP. The slides, which
can be downloaded here,
explain the rationale behind the multivariate analyses as well as a breakdown
of the findings related to Ad5 serostatus and circumcision status among male
volunteers. The slide set is best understood in conjunction with Susan
Buchbinder's presentation from CROI, which can be viewed online at http://www.retroconference.org/2008/data/files/retro2008_frameset.htm.
Phambili data released
On February 25, the NIAID issued a public statement with an
update on data from the Phambili trial of the Merck AIDS vaccine candidate,
MRK-Ad5. Phambili enrolled volunteers at four sites in South Africa.
Immunizations were halted in September 2007 following a recommendation from the
Data and Safety Monitoring Board for the STEP study, which also tested MRK-Ad5.
The NIAID update on Phambili is available
here. In brief, it reports that 801 participants had been enrolled at the
point when enrollment and immunizations were stopped in late 2007. In this
group (360 women and 411 men) there have been 11 HIV infections. All but one of
these infections were in women.
Seven infections were in vaccine recipients and four were in
the placebo arm. Among the seven vaccine recipients who became HIV-infected,
two received only one vaccination, four received two vaccinations, and one
received all three vaccinations.
By making the current
data available, NIAID, the HIV Vaccine Trials Network and the South African trial
partners continue to exhibit a high level of transparency. However no
conclusions can be drawn from these data. The numbers are too small to
support any scientifically-valid conclusions. As the report cautions, there was
a lot of variability in the length of time that various volunteers were
followed up.
Longer-term follow-up of volunteers will generate more data.
All Phambili participants now know whether they have received the vaccine or
the placebo. They have been counseled about the potential enhancement effect
associated with the vaccine, and vaccine recipients have been counseled about
intensifying their risk reduction. All of the volunteers have been asked to
continue returning for study visits, and all are receiving ongoing risk
reduction counseling along with condoms.
But even with additional data, there may never be clear
answers about the effect of MRK-Ad5 in this population. Now that volunteers have
been unblinded, meaning that volunteers know whether they have received the
vaccine or the placebo, this information could influence their risk-taking
behavior which could, in turn, influence rates of HIV in vaccine and placebo
groups. It will be difficult to interpret how the vaccine itself influenced
incidence rates.
Both the multivariate analyses and the raw data from
Phambili underscore the same point: the data from the MRK-Ad5 trials are
complex and may yield partial answers to some of our questions and, in other
cases, no answers at all. It is critical that the data which are available
continue to be shared openly and transparently. At the same time, advocates and
other stakeholders must communicate the range of unknowns which may persist
after all of the data analyses are completed, and that HIV prevention research
can and will continue in the context of these open questions.
What does this mean
for next steps?
Discussions about a re-designed PAVE 100 efficacy trial of a
DNA-adenovirus vector strategy are ongoing. A planned, early March meeting of
the NIH AIDS Vaccine Research Subcommittee to discuss proposed protocol
revisions has been postponed until after the "Vaccine Summit" described above.
AVAC is preparing a tool for advocates interested in learning more about the
discussions and issues related to the PAVE 100 decision and will release it to
the Network in the coming week. In the meantime, please do share your thoughts,
comments and questions about AIDS vaccine research priorities in general and
about PAVE 100 in particular with us at avac@avac.org.
Your input is a valuable contribution to AVAC's ongoing analysis and advocacy.
Thank you and please be in touch!
