The National Institute of Allergy and Infectious Diseases, part of the NIH, has discontinued the HVTN 505 clinical trial of an investigational HIV vaccine regimen because the vaccine did not prevent HIV infection nor reduce viral load among vaccine recipients who became infected with HIV, according to a NIAID statement.
An independent data and safety monitoring board (DSMB) found that 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.
The DSMB also found that the vaccine failed to reduce viral load among volunteers who acquired HIV infection at least 28 weeks after entering the study and who had been followed for at least 20 weeks after diagnosis. There were 30 participants with measurable viral load (15 vaccine recipients; 15 placebo recipients), according to an NIAID press release.
Therefore, the DSMB recommended that no further vaccinations with the investigational vaccine regimen be administered.
The investigational HIV vaccine regimen involved a series of three immunizations during an 8-week period, beginning with a DNA-based vaccine designed to prime the immune system. The priming vaccine series was followed by a single injection at week 24 with a recombinant vaccine based on a weakened adenovirus type 5 (Ad 5). The adenovirus was used as a vector of genetic material expressing a matching set of HIV antigens. Structures from all three major HIV clades were included.
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. During an interim review on April 22, 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. This was to allow enough time for the vaccine regimen to be given and stimulate an immune response.
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 nine HIV infections occurred among the placebo vaccine recipients.
According to NIAID, there was a non-statistically significant increase in HIV acquisition among volunteers in the investigational vaccine group compared with those in the placebo group, although the reasons are unclear and further analysis is needed.
The study investigators will continue following all study participants for 5 years from the time of enrollment.
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 2b study, conducted by the NIAID-funded HVTN External Web Site Policy, 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.