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 The prime-boost approach utilizes Sanofi Pasteur’s ALVAC-HIV vaccine as a prime and AIDSVAX (originally made by Genentech) as a boost.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