The Search for an HIV vaccine

I'm Paige Bates and this is The AIDS Pandemic

The RV144 study was a phase III HIV vaccine trial conducted by the
US Army and Thai government over seven years on 16,402
volunteers—all HIV negative men and women between the ages of 18
and 30 in parts of Thailand. For ethical reasons, all participants
were taught HIV prevention behaviors, given condoms, and promised
lifelong antiretroviral treatment if they contracted HIV. Half of
the volunteers were given a prime-boost vaccine regimen and half
received placebo vaccinations. The prime-boost approach utilizes
Sanofi Pasteur’s ALVAC-HIV vaccine as a prime and AIDSVAX
(originally made by Genentech) as a boost. ALVAC-HIV is comprised
of a canarypox virus with three HIV genes grafted onto it. AIDSVAX
contains a recombinant gp120 protein found on the surface of HIV.
These vaccinations were combined because one was designed to create
antibodies and the other to alert white blood cells. These
vaccinations were focused on the two strains of HIV commonly found
in Thailand, but it is unclear whether this regimen would have any
benefit elsewhere in the world. The participants were regularly
tested for HIV for three years following the completion of the
vaccine regimen. In September, the companies and agencies which
implemented and funded the trial announced in a press release and
interviews that new HIV infections were observed in 74 of the 8,198
people who received the placebo, but in only 51 of the 8,187 given
the vaccine. They claimed that this was a statistically significant
31.2% reduction in infection. However, the vaccine did not reduce
levels of HIV activity in those who became infected and did not
appear to produce any neutralizing antibodies.

Source: Wall Street Journal, September 25, 2009

In the 1980s, top officials embarrassed themselves by predicting an
HIV vaccine in five years. Reminiscent of these overly optimistic
declarations, the backers of the RV144 trial claimed that “we now
have evidence that a safe and effective HIV vaccine is possible.”
In the first wave of press subsequent to the initial press release
and interviews, many reputable news sources, such as the San
Francisco Chronicle, New York Times, NPR radio and BBC news,
suggested that these results were highly encouraging, and some even
went so far as to suggest that this regimen might be the forerunner
or basis for a usable vaccine in the near future. The LA Times
suggested that these findings would “energize and redirect” the HIV
vaccine field. Many articles quoted Dr. Anthony S. Fauci, the
director of the National Institute of Allergy and Infectious
Disease which largely funded the $100 million dollar study, as
saying “I don’t want to use a word like breakthrough, but I don’t
think that there’s any doubt that this is a very important result.”
The Wall Street Journal suggested that this finding could be the
second “big game changer in AIDS research since the mid 1990’s”
with the advent of drug cocktails. Many articles later qualified
with the cautionary statement that much more research is necessary
before the vaccine could be available to the public. Phrases urging
the public to be “cautious” but “hopeful” and describing the
results as “modest” yet “encouraging” rang throughout the media and
press releases.

However, only days later, the LA Times wrote “By Thursday
afternoon, the initial wave of euphoria had given way to the
recognition that many vexing questions will have to be answered
before researchers can produce a vaccine that will reliably shield
people from HIV.” Experts predicted that it would require two to
three years of research to unravel how and why the vaccine regimen
worked, and then an additional five to ten years to produce a
vaccine that was ready to test in people. The fact that this still
overly optimistic statement was a step back from the “initial
euphoria” shows the extent of the preliminary sensationalism. The
media reported that the researchers would now compare the blood of
those who were vaccinated and resisted infection, and those who did
not in order to determine whether the regimen stimulated antibodies
or other protective molecules against HIV infection. In an article
entitled “If AIDS went the way of smallpox,” a New York Times
reporter recognized many problems with the initial reports
including that many headlines in the first 24 hours after the press
release read “One Third Protected,” while in reality the margin of
success was “razor thin.” In addition, even the experts overseeing
the trial could not explain why blending two failed vaccines
suddenly resulted in “working” vaccine. Finally, this article
recognized the financial difficulties surrounding a regimen that
requires six shots over the span of months resulting in minimal
protection. While this might be practical in rich countries, AIDS
generally burdens the poorest nations in this world. Only one
article mentioned that some researchers were suggesting that the
apparent reduction in infections might be a statistical fluke due
to the small number of HIV infections observed. Throughout all
articles, there were minimal reminders to keep vigilance about
prevention, testing, and the necessity to utilize current
retroviral care.


Source: Wall Street Journal, October 12, 2009

In 2004, there was so much skepticism about this trial that 22 top
AIDS researchers published an editorial in Science magazine
suggesting it was a waste of money. Five years later, the
organizations which conducted the trial announced in a press
release that there has been significant protection, before making
the scientific data available to peer review. When the full details
of the study were released on October 20th at a meeting in Paris,
the statistic frailty of the study was revealed. The vaccine was
not shown to protect people at the highest risk of HIV infection.
As The Washington Post noted on October 21st, when the results are
analyzed using alternate methods, the protection is no longer
statistically significant. For example, when only the people who
received all six injections are counted, the trend towards
protection is no longer significant. This raises many questions.
What are the societal implications of the press surrounding this
vaccine? If this vaccine doesn’t have much, if any, effect, what is
the societal consequence of the data being overstated? The
possibility of a public backlash against vaccination efforts
wouldn’t be too hard to imagine. In fact, Gregg Gonsalves, an AIDS
activist, remarked that, “When this was rolled out a couple of
weeks ago, it was terribly hyped by the investigators. Some people
think that you have to dangle the slimmest morsels of hope in front
of the general public in order to keep them interested in an AIDS
vaccine. But I think that damages the credibility of the effort.”
The extent to which these results might represent a breakthrough
can only be determined after the mechanism behind the possible
conferred immunity is discovered. As Gonsalves points out, the
over-exaggeration of the success in the media will likely hurt the
results of the study if they prove to be less remarkable than
originally stated. Furthermore, this study raises a general
question about scientific results: is it appropriate to have news
press releases before data is available for full review by
scientific peers?

While this trial may not have been the scientific breakthrough that
it was praised as, at the very least, this tremendous study is an
example of international and interagency collaboration in
conducting a large-scale vaccine trial, including the Thai and US
governments, private companies such as Sanofi Pasteur, and
non-profit organizations such as Global Solutions for Infectious
Diseases (GSID). In this regard, it provides incredible hope for
HIV vaccine efforts in the future.

For more information, please see these articles.
US Military Research Program in Thailand

BBC news coverage of RV144


The Wall Street Journal: Data Call ito Question HIV Study Results