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. The two investigational vaccines tested in HVTN 505 cannot cause HIV infection because neither contains live or weakened versions of HIV.
The HVTN 505 study enrolled 2,504 volunteers at 21 sites in 19 US cities. The study population consisted of men who have sex with men and transgender people who have sex with men. In its April 22 interim review, the DSMB examined the information gathered from 1,250 volunteers who received the investigational vaccine regimen and 1,244 volunteers who received the placebo vaccine. The primary analysis looked at volunteers who were diagnosed with HIV infection after having been in the study a minimum of 28 weeks.
In this analysis, 27 HIV infections occurred among the vaccine recipients, and 21 HIV infections occurred among the placebo vaccine recipients. Among volunteers who became HIV-infected during the first 28 weeks of the study, 14 cases of HIV infection occurred among those who received the investigational vaccine regimen, and 9 HIV infections occurred among the placebo vaccine recipients. Overall in the study from the day of enrollment through the month 24 study visit, a total of 41 cases of HIV infection occurred in the volunteers who received the investigational vaccine regimen and 30 cases of HIV infection occurred among the placebo vaccine recipients.
Based on these findings, the DSMB recommended that no further vaccinations with the investigational vaccine regimen be administered. As the trial’s sponsor, NIAID concurred with the DSMB’s recommendation and has instructed all HVTN 505 study sites to immediately cease administering injections but continue follow-up with study participants to further evaluate the trial data.
Study investigators at each of the 21 clinical trial sites have been informed of the decision to stop immunizations in the HVTN 505 study and are contacting study volunteers to inform them of the developments. Individuals who became HIV-infected during the trial were referred to local services for appropriate medical care and treatment. The study investigators will continue following all study participants for five years from the time of enrollment.