The first clinical trial in the Bay Area to test the effectiveness of an AIDS vaccine was launched this week through a joint project of the San Francisco Department of Public Health and the University of California San Francisco. Known as a Phase III trial, the DPH/UCSF study will focus on the ability of the test vaccine to protect the body against HIV infection. It is part of a three-year, multi-site clinical research effort that is the first in the U.S. to look specifically at this aspect of a test vaccine.
The test vaccine is produced through genetic engineering techniques, so it is a synthetic product and does not contain any live virus. It cannot cause HIV infection.
The test vaccine product, named AIDSVAX, was developed by VaxGen, a biotech company based in Brisbane, Calif. The overall trial is being carried out at more than 50 locations throughout North America with the goal of enrolling 5,000 participants.
The DPH/UCSF team hopes to enroll 300 study volunteers. Study co-directors are Susan Buchbinder, M.D., chief of the HIV Research Section at DPH, and James Kahn, M.D., associate professor in the UCSF Positive Health Program at San Francisco General Hospital Medical Center.
The test vaccine is designed to train the immune system to develop a defense mechanism against the outer covering of HIV so the virus fails to spread throughout the body. It is not known if this approach will be effective in protecting the body against infection. Learning the answer is the overall objective of the Phase III trial.
In order to take part, volunteers must be adults who currently are HIV-negative and at risk for HIV infection through sexual exposure. All volunteers will receive extensive counseling that will focus on reducing the chance of becoming exposed to HIV.
The trial is a "double-blind" study with some participants receiving the test vaccine and some participants receiving a placebo, an inactive substance used as a comparison. Neither the volunteers nor the research staff will know which product is being administered. Participants receive the test vaccine by injection.
The DPH/UCSF researchers emphasize that this trial involves a test vaccine. They will not enroll anyone whose motive for participation is to use the vaccine as a reason to increase risky exposures by counting on the vaccine to act as protection against HIV.
"Participating in this trial is one way to make an important contribution to HIV vaccine research. But enrolling in this trial is not a replacement for safe sex," Buchbinder stressed.
Organizing the trial involved careful consideration of several ethical issues, added Kahn.
"The bottom line is that we want all the participants to be as safe as possible--whether they are in the vaccine group or the placebo group--and for this reason, counseling is an integral part of the trial," he said. "If participants follow some of the risk-reduction advice, it may influence the outcome of our trial. That is fine with us. The goal is to prevent new infections. We still feel our results will be valid in learning about the protective nature of a vaccine."
Earlier clinical studies of this vaccine evaluated its overall safety, including how it affected the immune system and whether it caused any adverse reactions in research volunteers. Results of these studies, the Phase I and Phase II trials, showed the vaccine to be safe in humans so far, and ready for evaluation at the next level.
The test vaccine contains two different synthetic versions of gp120, a protein found on the outer coating of HIV. The vaccine is designed to stimulate the body to produce white blood cells that specifically recognize the gp120 protein and then produce antibodies to gp120. Vaccine researchers hope that these antibodies will be able to recognize and bind to the gp120 protein on the surface of real HIV when it infects the body, thereby preventing the virus from invading the body's immune system and setting up the mechanism of continued HIV infection. Study participants will undergo a series of seven vaccine injections over a 30-month period. Blood samples will be taken and other tests conducted at regular intervals. Volunteers can enroll either through DPH or UCSF. Interested persons should call 415-514-4822 for complete information.
"It will take a sustained and probably lengthy effort to develop a vaccine that stops HIV in San Francisco and around the world," said Mitch Katz, M.D., director of DPH. "This trial is a new and important step in fulfilling that commitment."
Thomas Coates, Ph.D., director of the UCSF AIDS Research Institute, said, "This DPH/UCSF study represents the best in clinical research: using our local research strengths collaboratively and taking new steps in the path towards a preventive AIDS vaccine."
"We will greatly benefit from the expertise these two research groups bring to this important clinical trial," said Don Francis, M.D., D.Sc., president of VaxGen. "As a Bay Area company, we are pleased to be working with the people of San Francisco to test this vaccine."
Both the DPH HIV Research Section and UCSF have been active in HIV vaccine research over the past 7 years.
DPH has a long history of working with people at risk for HIV infection since the 1970s, when it conducted studies of hepatitis B in San Francisco. This research provided the foundation for some of the earliest studies of the AIDS epidemic.
A UCSF team at San Francisco General established one of the nation's first HIV/AIDS units 15 years ago. It has developed into a comprehensive service with extensive programs in clinical care and research. Some of the newest programs focus on people who are at high risk for HIV infection, such as the Options project and Post-Exposure Prevention project.
In addition to the North American trial, VaxGen plans to enroll a group of 2500 men and women in Bangkok to test the effectiveness of a version of the vaccine tailored for HIV strains common in Thailand.