AT THIS CONFERENCE, THE GOOD NEWS CAME FIRST . . .
BARCELONA, SPAIN – As attendees depart for far flung corners of the earth, the final sessions of this AIDS vaccine conference addressed the unsettling questions lingering over the results of three halted clinical research trials for which follow up studies continue. These are the questions: As each trial was halted because the product tested was found ineffective, how significant was data showing the product being investigated not only didn’t reduce incidence of HIV among those testing it, but instead appeared to increase the risk? What did that data mean? And what will that data mean in the future, not only for what will be tested, but how trials will be conducted?
While researchers reiterate that no trial that produces information can be called a failure, those questions, surrounding the Step HIV vaccine trial, and the Phamibili HIV vaccine trial, both of which were halted for futility in 2007, as well as the HVTN 505 trial, halted in April, have added to disappointment at the findings of each. The answers to the questions have suggested the one conlcusion that researchers seek to avoid: the disturbing implication that harm was done.
Today researchers discussed the implications of what they had learned so far, with an analysis of data from the three trials together showing an approximately 33 percent greater risk of HIV infection among trial participants given the investigational vaccine product compared to those who received a placebo.
Take away data from the most recent trial, and the increased risk of HIV infection using the product goes up. The HVTN 505 trial used a different approach, but the same means — a common cold-related virus — to introduce the immune-invoking ingredient, and took place solely in the United states. Data that indicated the possibility of an increased risk for those receiving the vaccine compared to those receiving the placebo has since been found statistically insignificant.
That leaves the data from the Step trial which took place at sites in the United States, South America, the Caribbean and Australia, and the Phambili trial which took place in Soweto and Capetown, South Africa. The increased rate of infection was most marked among participants in the Phambili trial.
Of 801 Phambili participants, 100 acquired HIV, 63 among those given the product, and 37 among those given the placebo.The trial stopped administering shots in the wake of futility findings with the suggestion of increased infections in the Step trial, with most of the Phambili participants having received no more than one or two shots. Then, at the request of the data safety monitoring board, participants were informed if they had received product or placebo. While that information was deemed pertinent to participants’ right to know and safety, it also clouded the results that followed as more infections accrued among product receivers than placebo receivers. Did knowing they had taken a product intended to protect them from HIV lead some participants to take more risks than those who knew they had received nothing even intended to have a protective effect? And if so, what could be done differently?
In answer to the first question, researcher Glenda Gray discussed the “confounding” effect (scientists’ as well as regular peoples’ talk for information that obfuscates efforts to draw a conclusion) of the participants knowledge, after the fact of whether they took a placebo or product. But, when all had been reviewed, she said, the factor driving the difference in HIV infection rates “was, in fact, biological.” The common-cold virus that was used to carry the vaccine product will not be used again, researchers here say with some confidence. And the participants of HVTN 505, as well as of Phambili, will continued to be followed.