Lessons learned from the HVTN 505 HIV vaccine clinical trial
May 2, 2013
Emory researcher Dr. Mark Mulligan discusses results of recent HIV vaccine study and how it aids them in the search for an effective and safe vaccine for HIV.
Further Commentary by Mark Mulligan
In the 32 years since AIDS was described in 1981, only four types of HIV vaccines have been tested in six HIV vaccine efficacy trials. The efficacy trial is the final stage of clinical research that asks the penultimate question: does the vaccine protect people against HIV/AIDS?
The HVTN 505 clinical trial was designed to test whether an investigational HIV vaccine regimen could protect against HIV/AIDS. The trial began in 2009 and enrolled 2,504 volunteers at 21 sites in 19 U.S. cities. The Emory Vaccine Center’s Hope Clinic was the second highest enrolling site in the country, with 194 study volunteers enrolled. Locally we also referred to this study as LifeForward.
In disappointing news last week, we learned from the independent Data and Safety Monitoring Board (DSMB), which has been closely monitoring this clinical trial, that the vaccine regimen was ineffective. It did not prevent HIV infection or reduce the amount of virus (viral load) in the blood among people in the study who became infected with HIV.
Because of this result, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), asked the study sites to stop administering injections of the vaccine.
The study population consisted of men who have sex with men and transgender people who have sex with men. The study, conducted by the HIV Vaccine Trials Network (HVTN), was divided into two groups – those that received vaccine and those that received a placebo. All participants were offered extensive counseling on how to reduce their risk of becoming HIV-infected and provided free condoms.
The vaccine regimen was a combination of two HIV vaccines, beginning with a DNA-based vaccine designed to prime the immune system. The DNA priming vaccine contained genetic material expressing proteins from both the surface and internal structures of HIV. Three immunizations with this vaccine were followed by one injection of a booster vaccine based on a weakened adenovirus type 5 (Ad 5). The adenovirus was used as a vector, or carrier, of genetic material expressing a matching set of HIV proteins.
Adenoviruses are a common cold virus, but the Ad5 virus used in the study was disabled so that it could not cause a cold or other respiratory illness. And the two investigational vaccines tested in HVTN 505 could not cause HIV infection because neither contains live or weakened versions of HIV.
At the time the study was reviewed, there were somewhat more new HIV infections among participants (nationwide) who received the vaccine than those who received the placebo after the full vaccination series: 21 infections in the placebo group compared to 27 in the vaccine group. But this difference was not significant in a statistical analysis, meaning it could have occurred by chance.
Hope Clinic staff members have contacted all study participants individually to discuss results and to arrange health care follow up. All study participants will continue to be followed for five years from the time of enrollment. NIAID and the HVTN 505 study team are working to thoroughly analyze the study data to better understand why the vaccine did not work and to guide future vaccine development efforts.
Of course this is a disappointing result for our researchers and for the community. Many scientists have worked diligently for decades to find an effective HIV vaccine, and we continue to believe that a vaccine is both possible and essential for curbing and eventually eliminating this global disease.
This study allowed us to find answers to its two main research questions, and we are very grateful for the participation of community volunteers as a critical part of this research. Everything we learn from each clinical trial helps guide us in future vaccine development. The Atlanta community and Emory University are leaders in this effort.
Our clinical research team and our laboratory researchers in the Emory Vaccine Center continue to be committed to finding an effective vaccine, and there is a great deal of exciting and promising research underway in both areas. While disappointing, this result is not a dead-end, rather it is a delay or a detour, on the road of vaccine research. We are constantly moving closer to the goal of a safe, effective vaccine to prevent HIV/AIDS.
Mark J. Mulligan, MD, is executive director of The Hope Clinic of the Emory Vaccine Center, a professor of medicine in Emory University School of Medicine, and a co-director of the Clinical Research Core of the Emory Center for AIDS Research.