Immunizations Halted in HIV Vaccine Trial
An HIV vaccine trial underway in 19 U.S. cities halted immunizations this week after an interim review revealed that the injections neither prevented HIV infection nor lowered HIV viral load in those who became infected. Participants in the HVTN 505 trial will continue to be followed but will not receive further injections with the investigational vaccine or the placebo.
HVTN 505 is evaluating the safety and efficacy of two different vaccines in a strategy known as “prime-boost.” The first vaccine contains material designed to mimic HIV’s own antigens (molecules that help the body identify viruses and other invaders) and was delivered in three injections over an eight-week period. This series was meant to “prime” the immune system to produce antibodies against HIV. The second vaccine is a single shot containing a common cold virus that was genetically modified to carry a “matching set” of those antigens; this immunization, given at week 24, was designed to “boost” the immune response.
The study had enrolled 2,504 HIV-negative men who have sex with men and transgender people who have sex with men. To participate, all male volunteers were required to have been circumcised, and all participants had to be free of antibodies to the Ad5 common cold virus—eligibility criteria established in response to the Step Study, “which found in 2007 an increased number of HIV infections among vaccine recipients, particularly those who were not circumcised and/or had Ad5 antibodies,” explains a Q&A page about the study.
In the HVTN 505 trial, “there was a non-statistically significant increase in HIV acquisition among volunteers in the investigational vaccine group compared to those in the placebo group,” according to a statement from the National Institute of Allergy and Infectious Disease (NIAID), which sponsored the study. “It is not clear why this occurred and further analysis is needed to draw any firm conclusions.”
“The vaccines do not contain any live or killed HIV, and cannot transmit HIV to those who were vaccinated,” emphasized a statement from Susan Buchbinder, MD, director of Bridge HIV, the HIV research section of the San Francisco Department of Public Health. Bridge HIV is one of 21 study sites conducting the HVTN 505 trial.
What’s next for study participants? “Study volunteers are being asked to report to their specific clinic sites over the next few weeks to find out whether they received the investigational vaccines or placebo injections,” explains the NIAID Q&A. “The study investigators will continue following each participant for five years after their enrollment in the trial.”
“We, at Bridge HIV, want to thank all of the participants who enrolled at our site, and around the United States, for their commitment to finding an effective HIV vaccine,” Buchbinder’s statement adds. “Their dedication will bring us one step closer to having a safe and effective global vaccine for the future.”
To learn more about the HVTN 505 trial, the changes announced this week, and the implications for HIV vaccine research, see the NIAID statement excerpted below and available at niaid.nih.gov.
April 25, 2013
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, will stop administering injections in its HVTN 505 clinical trial of an investigational HIV vaccine regimen because an independent data and safety monitoring board (DSMB) found during a scheduled interim review that the vaccine regimen did not prevent HIV infection nor reduce viral load (the amount of HIV in the blood) among vaccine recipients who became infected with HIV.
The HVTN 505 study began in 2009 and was testing an investigational prime-boost vaccine regimen developed by NIAID’s Vaccine Research Center. The Phase IIb study, conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN), was designed to determine whether the vaccine regimen could prevent HIV infection and/or reduce the amount of virus in the blood of vaccine recipients who became infected with HIV.
The investigational HIV vaccine regimen involved a series of three immunizations over the course of eight weeks, beginning with a DNA-based vaccine designed to prime the immune system. The DNA priming vaccine contained genetic material expressing antigens representing proteins from both the surface and internal structures of HIV. Immunizations with the priming vaccine were followed by a single injection at week 24 with a recombinant vaccine (the 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 antigens. Structures from all three major HIV clades, or subtypes, were included. Adenoviruses are a common cold virus, but the Ad5 virus used in the study’s vaccine regimen was disabled so that it could not cause a cold or other respiratory illness. The two investigational vaccines tested in HVTN 505 cannot cause HIV infection because neither contains live or weakened versions of HIV….
For more resources on HIV vaccine development—including fact sheets and timelines for ongoing trials around the world—visit the AIDS Vaccine Advocacy Coalition’s vaccine page at avac.org.
Reilly O’Neal is the editor of BETA.