A secondary analysis of data from the Thai AIDS vaccine trial -- announced last month to much acclaim -- suggests that the vaccine might provide some protection against the virus, but that the results are not statistically significant. In short, they could have come about merely by chance.
Initial results from the trial involving more than 16,000 people had shown that the vaccine reduced infections by about 31% and that the results, though limited, were statistically significant. But the new analysis, which was part of the trial protocol, showed that it seemed to reduce infections by 26%.
Results from the secondary analysis have been circulating for a couple of weeks, but the full results of the trial did not become available until they were published online in the New England Journal of Medicine and announced today at a conference in Paris.
In an editorial accompanying the journal paper, Dr. Raphael Dolin of the Beth Israel Deaconess Medical Center in Boston said the overall findings were nonetheless "of potentially great importance to the field of HIV research" because they might yield information about the kinds of immune responses necessary to provide protection against the virus.
But Dr. Otto Yang, an immunologist at UCLA's Geffen School of Medicine, cautioned that "the results are weak enough that we need to be very careful about assigning too much optimism to them. . . . It seems not so likely that the vaccine really did what it was intended to do."
The trial, sponsored largely by the National Institute of Allergy and Infectious Diseases, combined two different vaccines -- each of which had proved ineffective in previous trials -- in the hope that one would prime the immune system and the second would boost immunity.
The key difference between the two types of analyses is that the original one excluded seven patients who were found to have HIV infections at the time the study began. The new analysis, based on what is called an intention-to-treat analysis, included all patients who were originally enrolled in the trial, producing the weaker results. Vaccine trials are typically analyzed both ways, and researchers expect to see statistically significant results from each analysis.
The fact that they did not in this case suggests that any effects of the vaccine were exceptionally modest.
Also concerning is the observation that, among those who were vaccinated and subsequently caught the virus, the infection was as severe as it was in those who were not vaccinated. If the vaccine had stimulated any kind of immune response, the infection should have been less severe in those who were vaccinated.
The question now, Yang said, "is how much time and energy do we want to spend chasing these results? . . . Or should we simply discount it and use the resources for newer vaccine ideas?"