Fallout and Frustration: Merck�s failed HIV vaccine trials
Duane Wells | November 29, 2007
Just a few short months ago, a spirit of cautious optimism surrounded the prospects for a viable HIV vaccine. As Merck began testing its highly anticipated V520 vaccine, which it had reportedly been developing over a ten year period, there was an undercurrent of excitement among researchers in the HIV community about the radical new approach, which was expected to attack, seek out, and destroy infected cells. There was a sense of promise: For the first time in years, the study might yield a significant breakthrough in the ongoing fight to contain the global HIV/AIDS epidemic.
Two months into the study, those hopes were dashed and the HIV community sent reeling as the international Merck trials were shut down after preliminary results demonstrated that the vaccine appeared to be doing more damage than good.
With researchers collectively scratching their heads in confusion, the Merck failure has created some serious impediments for future HIV vaccine trials, forcing the HIV research community to rethink its science, priorities and goals.
The Merck HIV vaccine trials included 3,000 participants, mostly male, in North and South America, the Caribbean and Australia, all of whom were considered to be at high risk of exposure to the virus because of their sexual activity or drug use.
Unlike previous experimental HIV vaccines that attempted to stimulate the body to produce antibodies that would ward off infection, Merck's V520 focused on T-cells that attack and kill cells that HIV had already infected.
But rather than stimulate an immune response to ward off HIV invasion, the vaccine, which employs a few synthetic fragments of HIV loaded onto a genetically modified cold virus (called an adenovirus) may well have altered the immune system to facilitate infection of study participants. Moreover, the vaccine did not reduce viral loads in volunteers who became infected with HIV during the trial.
Despite this disappointing initial data, there are those in the HIV research community who insist that all hope is not lost.
The first piece of good news: Though the V520 vaccine may have increased the chance of infection, Merck along with the majority of HIV experts agree that the vaccine itself did not and cannot cause HIV infection.
The other piece of good news to come out of the Merck HIV Vaccine trials is that there are valuable lessons to be learned from its failure. According to Dr. Stephen J. Brown, Medical Director for AIDS Research Alliance, which was the only Los Angeles site conducting clinical trials for the Merck Vaccine, "The closing of the Merck vaccine study may have an important impact as to the future of most HIV vaccines candidates currently in clinical trials because, like the Merck vaccine, many are designed to similarly stimulate strong cell-mediated immune responses."
Further, in a published statement, AIDS Research Alliance was quick to not discount the outcome of the Merck experiment.
"The results of this study may also provide valuable information as to the future direction of HIV vaccine research. Since all vaccine candidates in the pipeline are designed to stimulate only one arm of the immune system, maybe an efficient vaccine against HIV will need to stimulate both arms (including neutralizing antibodies, or other cells such as natural killer cells) of the immune system in humans," the statement said.
Despite these arguably positive, if unanticipated, results, there remains substantial concern about the long-term perception that the high profile failure of the Merck trial might have on future studies.
According to the Philadelphia Inquirer, Hildegund C.J. Ertl, an immunologist at the Wistar Institute in Philadelphia, who is preparing to test another HIV vaccine based on a chimpanzee cold virus next year, has said that the Merck effort will likely alter her study.
Gary J. Nabel, director of the Vaccine Research Center of the National Institutes of Health, has postponed until at least mid-2008 his group�s PAVE 100 HIV-vaccine trial. That trial uses three shots of DNA followed by a cold-virus booster, albeit one with different components from the Merck product.
Meanwhile, according to various news reports, The National Institutes of Health, which helped sponsor Merck's aborted clinical trial, recently halted recruitment for vaccine trials involving several diseases, including Ebola, because those vaccines, like the failed Merck one, are made with an adenovirus.
Perhaps the greatest problem that lies ahead for future HIV vaccine studies may not be the science or the trials themselves but the recruitment of now skittish volunteers to take part in them.
�I can tell you that as a volunteer in the study, and as someone who worked on the last phase III clinical trial of an AIDS vaccine, I�m less disappointed than I am scared by the early results of this trial,� says Jim Key, Chief Public Affairs Officer for the Los Angeles Gay & Lesbian Center. �What scares me, of course, is the indication that study volunteers who received the product, and not the placebo, may be at greater risk of HIV-infection than those who didn�t receive it. This is a scary concern not just for volunteers in the study, but for the success of future studies. It�s already difficult to recruit volunteers for vaccine studies. The results of this trial are likely to make recruitment for future studies considerably more difficult.
�I don�t believe hopes were high for the Merck vaccine, so I�m not overly surprised it didn�t prove efficacious,� Key added. �What�s important to remember, however, is that every clinical trial of a vaccine helps advance the science and if we don�t continue to develop and test promising vaccines we�ll never stop AIDS.�
Still others like Michael Weinstein, President of AIDS Healthcare Foundation, seem to believe that the implosion of the Merck trial is only more indicative of the need to balance the quest for a vaccine with developing long-term treatment options and the availability thereof.
�Development of a safe and effective AIDS vaccine is clearly a noble and worthy goal; however, the sad truth remains that more than 33 million people worldwide are living with HIV/AIDS today, yet barely two million of them have access to lifesaving antiretroviral AIDS treatments, Weinstein said in a statement.
�Treatments that actually do work and help keep those fortunate enough to have access to them alive and well, and which also have also been around, and continually improved, for over a decade. These recent failures in vaccine development underscore just how tenuous the quest for an AIDS vaccine remains, and reminds us of what effective, but underused tools, including antiretroviral treatment, we already have available to us today. While we long for the day when there is an effective preventive AIDS vaccine, we also call for a reevaluation of the distribution of limited government resources in the battle against AIDS, and renew our call for a greatly stepped-up commitment to bringing antiretroviral treatment to many, many more of those people still in need worldwide.�
The final effects of the collapse of the Merck HIV vaccine trials may not be seen for quite some time to come. Whether the results of the study will ultimately help or hinder HIV research is debatable, but one thing is for certain. Though hope for a vaccine may spring eternal, its prospects have, for the moment, most certainly been dealt a short-term setback at minimum. – Issued by Gay Link Content
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