WedSeattle, Washington, November 7, 2007, The AIDS Vaccine Advocacy Coalition (AVAC) released the following statement today from Executive Director Mitchell Warren in response to the release of new data from the STEP AIDS vaccine study by Merck & Co., the US National Institute for Allergy and Infectious Diseases (NIAID) and the HIV Vaccine Trials Network (HVTN) at a public forum at the HVTN meeting today.

The data from the STEP study released today confirm that the vaccine was not effective at either preventing infection in male volunteers or at reducing viral loads in male vaccine recipients who became infected with HIV during the trial. In addition, the data suggest that the vaccine may have made some volunteers more susceptible to acquiring HIV infection. The vaccine itself does not cause HIV. This trend was specifically observed among male volunteers who had high titers of antibody to adenovirus, the cold virus that was used, in a disabled form, in the MRK-Ad5 vaccine candidate.

“These data are deeply disappointing and troubling, and raise more questions than answers for the field of AIDS vaccine. Today’s discussion of the data underscores the leadership and transparency that Merck, NIAID, and HVTN continue to show in this complex and challenging time. What is clear is that the field must continue to work on this challenge and on the larger goal of finding a safe and effective AIDS vaccine.

“As much as we would like to see a clear answer in these results to whether or not the vaccine made some volunteers more susceptible to HIV infection, the reality is that there is still significant confusion about the underlying explanation for the observed effect.

“As we move forward, the work of analyzing and interpreting the data from the STEP study, and from the companion Phambili study in South Africa, will become even more difficult and even more important.

“In the weeks and months to come, we look to the AIDS vaccine field as a whole to maintain a collaborative spirit and to commit all necessary resources to the critical work of understanding the potential explanations and implications for the trends observed in the STEP study.

“We commend the trial sponsors for their consistent commitment to the safety of the volunteers, which must be the top priority in this and every other HIV prevention trial. At every stage of this difficult process, trial sponsors and site-level staff must continue to clearly communicate key information about the data and the participants’ potential risk to volunteers at every site.

“AVAC recognizes that these data leave the AIDS vaccine field with a range of difficult decisions.  Going forward, we believe that the wisest course of action is also the most cautious. To safeguard future trials and  volunteers, the trial sponsors and the field as a whole should take as long as is needed to analyze the data and attempt to come to more definitive conclusions about what these new data mean, before beginning efficacy trials of other vaccine candidates.

“In addition, if there is the possibility that unblinding the STEP study and informing every participant about whether he or she received the placebo or the vaccine will provide an additional safeguard for participants, then this is the course of action that should be taken. AVAC believes that ultimately the decision about unblinding the trial should be guided by the participants’ own concerns and priorities.

“Above all, we must continue to see this for what it is: a major setback for the AIDS vaccine field, but one that can and must be overcome through rigorous scientific investigation, open communication with communities, and a firm commitment to the shared goal of reversing the course of the AIDS epidemic in our lifetimes.”

AVAC will continue to provide updates, analysis and resource materials at http://avac.org/pr_step_study.htm as the decision about unbinding the trial is made and as more analyses and data are released. 

New York and Johannesburg — The AIDS Vaccine Advocacy Coalition (AVAC) issued the following statement with regard to recent announcements about the Phambili AIDS vaccine trial in South Africa.

“We are deeply concerned by and share the disappointment of the field regarding the October 23 announcement that the immunizations would be stopped in the Phambili trial of Merck’s Ad5 candidate, and that volunteers in that study would be counseled that receiving the vaccine might have increased their risk of acquiring HIV infection,” said Mitchell Warren, AVAC executive director.

“This is a serious setback and heavy blow to the dedicated volunteers, principal investigators, and site staff who have committed their time, energy and optimismto this study. As always, we believe that participant safety is paramount and that where ever doubts arise, monitoring boards and trial sponsors must err on the side of caution.

“At this time, it is not clear whether or not there is definitive evidence that the vaccine did increase participant’s susceptibility. In the absence of this information, we must make sure that all participants in all of the trials of the Merck product understand the basis for the counseling messages about the possibility of increased susceptibility to HIV infection. We must also be cautious about leaping to definitive conclusions until the full data sets have been analyzed.”

On Tuesday, October 23, the South African AIDS Vaccine Initiative (SAAVI) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH) issued press statements stating that the Data and Safety Monitoring Board (DSMB) for the Phambili trial [HVTN 503] had reviewed the available data from the STEP study of the same candidate, which halted immunizations in September, 2007.

As the NIAID press release stated, the DSMB made several recommendations: “The DSMB also recommended that HVTN 503 volunteers be told whether they received the vaccine or placebo, be strongly encouraged to return to their study sites for protocol-related tests, and be counseled about the possibility that those who received the vaccine may have an increased susceptibility to acquiring HIV infections.”

“It is very important that the field put forward clear common messages,” said Pontiano Kaleebu, AVAC board member, and principal investigator on AIDS vaccine trials at the Uganda Virus Research Institute. “The search for an AIDS vaccine must continue even when there is bad news. To move forward, all of us — communities, investigators, sites, the media — must work together to convey accurate messages based on the information available.”

Additional data set from the STEP study will be released in a public discussion on November 7, 2007, at HIV Vaccine Trial Network meeting in Seattle, Washington. This meeting will include data on rates and timing of infection from the second 1500 volunteers enrolled in the STEP study.

“It is hoped that exploration of this additional data from STEP will add to our understanding of what happened in that trial, and shed additional light on many questions, including whether vaccine recipients did indeed have increased risk of acquiring HIV,” said Warren.

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About AVAC
Founded in 1995, the AIDS Vaccine Advocacy Coalition (AVAC) is a non-profit, community and consumer-based organization that uses public education, policy analysis, advocacy and community mobilization to accelerate the ethical development and global delivery of AIDS vaccines and other HIV prevention options. To help assure its independence, AVAC does notaccept funding from government or pharmaceutical industry sources. For more information, visit http://www.avac.org.

New York, September 21, 2007 — The AIDS Vaccine Advocacy Coalition (AVAC) released the following statement from Executive Director Mitchell Warren about the announcement that vaccinations have been discontinued in the STEP Study, a test-of-concept trial of the MRK-Ad5 AIDS vaccine candidate developed by the Merck Research Laboratories:

“Today’s announcement about the STEP Study is a deep disappointment and a scientific setback for the AIDS vaccine field. However, it must be seen for what it is: the failure of a product to show efficacy in a specific trial. Clinical testing of AIDS vaccines is a scientific process and, while this is a disappointment, it is in no way the end of the search for an AIDS vaccine.

“These data are certainly not the ones that we had hoped for. The entire HIV vaccine field, including AVAC, had been looking to STEP and its companion Phambili trial in South Africa, to provide initial evidence of vaccine-related benefits. Even as the data disappoint, we also note the success of the STEP Study trial design in providing a swift answer to the critical question of whether or not the vaccine provided any benefits. A successful clinical trial is one that produces a scientifically accurate result. It may not be the result you had hoped for, but it answers questions that help the field move forward.

“We applaud Merck’s tremendous leadership on HIV vaccine research. The company has set an example for the field, taking on one of the most important health technology challenges of our time. Merck and its collaborator, the US NIH-funded HIV Vaccine Trials Network, have been committed, strategic and willing to take risks at every stage of evaluating MRK-Ad5, and they must be commended for this. AVAC also recognizes the contributions of the thousands of volunteers in these trials. Their altruistic involvement makes HIV vaccine research possible. It is essential to build on what has been learned here and proceed with further research as rapidly as possible. Millions of lives are at stake.

“In the next weeks and months the AIDS vaccine field will need to make carefully-considered decisions about whether to move forward with planned trials of related vaccine strategies, and how to proceed with the Phambili trial, which has paused immunizations and enrollment. AVAC is committed to working with many other stakeholders in the AIDS vaccine field and in other areas of AIDS prevention research to ensure that these discussions are thoughtful, transparent, and clearly communicated to global audiences.

“These results do not change our fundamental view. Developing an AIDS vaccine will require a series of large-scale human trials in many different countries over a number of years. These trials need to be designed to produce clear results and to design better candidates in the future. This research must be complemented by ongoing studies of other new biomedical prevention strategies, and by full-scale, fully-funded implementation of proven prevention and treatment strategies.”

About the STEP Study
An interim analysis of data from the study, involving over 3,000 people testing an adenovirus-based vaccine (MRK-Ad5) developed by the Merck Research Laboratories, showed no efficacy in protecting against new infections or in reducing viral load in people who received the vaccine and went on to become infected. The study was scheduled to end in 2009. Periodic reviews of data by an independent monitoring board are part of the clinical trials process, and the study was halted on the recommendation of the STEP Study monitoring board after a regularly-scheduled review.

There have been two previous efficacy trials of an AIDS vaccine candidate, called AIDSVAX. Both of these studies took more than five years from launch to announcement of the finding, that the candidate did not protect against infection. The STEP Study enrolled its first participant in December 2004, and we have a definitive answer less than three years later. Getting swift, precise answers about candidates is crucial for the field. In this sense, the STEP Study fulfilled its purpose, as disappointing as the results may be.

One reason for this efficiency is that both STEP and its companion trial Phambili, which tested the candidate in South Africa, were designed as “test-of-concept” trials, to give an initial answer about vaccine benefits in a relatively abbreviated timeframe. The STEP Study met its enrollment targets and its endpoint goals within the timeframe specified by the trial planners.