Controversial HIV Vaccine Trial Results Disappointing

Preliminary results from a large study of a controversial vaccine designed to prevent HIV infection showed that, overall, it did not work.

In this trial, over the course of 30 months, volunteers (5,108 gay and bisexual men and 309 women at high risk for HIV infection) received up to seven injections of one of the following:

• an HIV protein in a formulation called AIDSVax (vaccine)
• a fake vaccine (placebo)

The vaccine was supposed to provide protection from the sub-type of HIV that is usually found in Australia, North America and Western Europe -- called "sub-type B." As a result, the vaccine was tested in Canada, the Netherlands and the United States.

Results

At the end of the study, the proportion of volunteers who received the vaccine or placebo and became infected with HIV was as follows:

• vaccine: 5.7%
• placebo: 5.8%

These results show that the vaccine failed in its main objective -- to protect people from HIV infection.

The manufacturer of the vaccine, VaxGen, presented data which suggested that some Asian and Black volunteers may have had a reduced risk of acquiring HIV infection because they received the vaccine. However, VaxGen's ethnic analysis is based on very small numbers of people who got HIV in vaccine and placebo groups:

• among Black people: 9 in the vaccine group; 4 in the placebo group
• among Asian people: 2 in the vaccine group; 2 in the placebo group

Because of such small numbers, it is "difficult to draw conclusions about what this means," said Dr. Seth Berkley, President of the International AIDS Vaccine Initiative (IAVI). This point is important when the overall size of the trial -- more than 5,000 volunteers is taken into account.

AIDSVax is made from an HIV protein called gp120. This protein helps HIV infect cells of the immune system. AIDSVax is designed to stimulate the immune system to produce antibodies that bind to gp120 and block the virus from infecting cells.

VaxGen's approach to HIV vaccine design has been controversial. Some leading HIV researchers suspect that different approaches to helping the immune system, such as stimulating killer T-cells that can control HIV, may be a more fruitful approach.

Next Steps

The United Nations AIDS program (UNAIDS) plans to convene an expert panel to discuss questions raised by the trial results. For instance, why were infection rates in some Asian and Black people apparently lower than in white and Hispanic people? Are there social, behavioural or genetic factors that could explain the results?

VaxGen plans to conduct many tests, including comparing the antibodies in the blood of volunteers who received the vaccine and became infected to antibodies in those who received the placebo and became infected, in order to find out if there is any difference. As well, the company hopes to discuss its findings with the American Food and Drug Administration (FDA) and seek this agency's advice about any further development plans. Another VaxGen vaccine is being tested in Thailand and results from that trial should be available later this year.

References

1. Anonymous. VaxGen Announces Initial Results of its Phase III AIDS Vaccine Trial. Press release. 24 February 2003. www.vaxgen.com/pressroom/index.html
2. Anonymous. Statement of IAVI's Seth Berkley regarding the results on VaxGen's AIDSVAX. Press release. 24 February 2003. www.iavi.org/press/2003/n20030224.htm
3. Francis DP, Heyward WL, Popovic V, et al. Candidate HIV/AIDS vaccines: lessons learned from the World's first phase III efficacy trials. AIDS 2003; 17(2):147-156.