Researchers from pharma giant Merck Inc. are concerned about a highly anticipated AIDS vaccine trial. There are fears of the recipients having become , on the contrary, more susceptible to HIV.
Researchers reporting yesterday at a scientific meeting in Seattle,
cited inadequate data to decipher the findings of this closely watched trial.
The increased risk was mainly among a group of people who had pre-existing levels of resistance to a common cold virus (adenovirus type 5). This virus was modified to become a critical part of the vaccine.
Though the researchers say that the vaccine itself could not cause AIDS, they hypothesize that the cold virus may have activated the immune system in some way to make certain recipients more to the AIDS virus.
At the same time, participants also emphasize that the findings could be a statistical fluke or that non-biological factors could have accounted for the difference.
Examples of such factors include rates of circumcision and sexual practices among trial participants.
In late September, Merck out of the blue, stopped the trial of its experimental H.I.V. vaccine. This was because it failed in its two main objectives, to prevent infection and to lower the amount of H.I.V. in the blood of those infected.
The vaccine was being tested among 3,000 volunteers at high risk of developing AIDS in nine countries, including those at immunization centers organized by the National Institutes of Health in the United States.
Hopes were high as Merck's vaccine was seen as one of the most promising experimental AIDS vaccines to have been tested on people. Those supporting the research have suffered a big setback.
"The new analyses are both disappointing and puzzling" because they offer no explanation for the vaccine's failure, says Dr. Anthony S. Fauci. He is the director of the National Institute of Allergy and Infectious Diseases and a partner in the vaccine trial.
In September, a preliminary analysis of about half those in this trial suggested that those vaccinated were becoming HIV-infected at almost the same rate as those receiving a placebo.
Yet, new analysis, which looked at all the trial participants, discovered a wider difference (49 in the vaccinated group compared with 33 in the placebo group).
Further analysis showed that the imbalance was much more common among those who had the highest level of pre-existing immunity to the cold virus used in the vaccine.
Out of 778 male volunteers who had a high level of pre-existing adenovirus immunity, 21 of those receiving the vaccine developed HIV infections compared with 9 in the placebo group.
The difference between the groups with low levels of adenovirus immunity was lesser (28 among the vaccine recipients compared with 24 who received a placebo). Compared to the former, this difference is not statistically significant.
Verification of this hypothesis will require future extensive laboratory tests.
Findings could determine the underlying biological mechanism responsible for the vaccine's failure. Unfortunately, it would take months to years for such tests to be completed, Dr. Keith Gottesdiener, a Merck vice president, was reported.
These new reports have created even more of a scientific muddle on the subject. The global HIV pandemic has infected an estimated 39 million people and killed 25 million more.
The findings raise questions about whether adenovirus could ever actually be used as a crucial ingredient in an AIDS vaccine.
Use of a modified virus as a vector to deliver HIV genes is a new and evolving way to make an AIDS vaccine. The Merck vaccine included three synthetic H.I.V. genes.
Yet, scientists and groups that advocate AIDS research say the vaccine failure should not lessen the commitment to develop a vaccine.
The AIDS Vaccine Advocacy Coalition, a community and consumer-based group has urged AIDS scientists not to begin trials of other new vaccines until more definitive conclusions could be reached from further analysis of the Merck vaccine.