Science A Disastrous End to the STEP HIV Vaccine Trial
posted by November 9 at 16:45 PMon
The news from the (once) most-promising candidate anti-HIV vaccine keeps getting worse.
Back in May I wrote about this entire class of vaccines:
After the failure to produce an infection-blocking vaccine, some groups have taken on a more modest goal: Make a vaccine that triggers a more vigorous counterattack, slowing or preventing the progression to AIDS and reducing the risk of transmission. Like being introduced to a blind date by a guy who mugged you last week, these vaccines give the immune system a memorably nasty reintroduction to the HIV proteins. The most promising vaccines stuff multiple HIV proteins, including less variable internal machinery proteins of the virus, in a cold virus engineered to be harmless. In animal tests and preliminary human trials these vaccines work better than initially expected, both slowing infections and in some cases even blocking initial infections. The results from human trials against wild virus are not complete—one major phase II trial’s results should be out in 2008.
Seattle is host to the NIH-funded HIV vaccines trial unit—the largest anti-HIV vaccine clinical trials unit coordinating trials worldwide. For the STEP trial, testing one of these cold-viruses-carrying-HIV-protein vaccines, three thousand volunteers were recruited worldwide, including 119 gay men in Seattle.
The HIV-negative volunteers were randomized to either receive the experimental vaccine or a placebo. After the three injections, the participants were followed to compare what percentage of the vaccinated versus non-vaccinated got HIV, and how their HIV progressed. Everyone received HIV-avoidance counseling.
Back in September, the STEP trial testing this vaccine was “discontinued [PDF] because the vaccine was not effective.” By this point, all the men randomized to receive the vaccine in Seattle had received all three injections.
This week, more bad news was released:
The current STEP results suggest that those who received the vaccine might have an increased susceptibility to acquiring HIV infection, particularly those volunteers who had higher levels of pre-existing immunity to Ad5 because of prior natural exposure to Ad5. However, there are a number of confounding factors that make it very difficult to draw conclusions about this finding.
In other words, if you’ve had a very common adenovirus cold virus infection in the past, and received the experimental vaccine, you might be more susceptible to HIV infection. Perhaps for the rest of your life.
One criticism of the Adenovirus 5 based vaccines is something known as original antigenic sin. An immune system previously exposed to a wild version of Adenovirus 5 retains a memory of the infection. When exposed to the vaccine, the immune system might simply reactivate against the cold virus proteins rather than the new HIV proteins, and therefore fail to properly protect against HIV. These concerns seemed to be true.
Seattle—young, gay—has hosted many vaccine trials, including several failed HIV vaccines, the Herpes vaccine still undergoing testing and the successful HPV vaccine. Volunteering for any experimental treatment is a deeply altruistic act—risking your health to help those in the future. We owe a debt of gratitude to the STEP volunteers, as well as the people around you who volunteered for the other vaccine trials. Given the disastrous results of this trial will—or should—Seattlites continue to volunteer?
If you were a volunteer for this study, e-mail me at email@example.com