The US National Institute of Allergy and Infectious Diseases (National Institute of Allergy & Infectious Diseases (NIAID)) announced that HVTN 702, a large-scale HIV vaccine efficacy trial of a canary pox-based vaccine candidate, has been stopped following an interim review because the vaccine does not prevent HIV.
The trial, which began in October 2016, was evaluating HVTN 702 (also known as Uhambo). The trial enrolled 5,407 sexually active, HIV-uninfected men and women between 18 and 35 years of age at 14 sites across South Africa. Researchers randomly assigned half of the subjects to receive a pair of HIV vaccines used in a prime boost, whereas the other half received placebo shots. The trial was scheduled to conclude in July 2022. However, an independent monitoring board informed the leaders of the study that it was “futile” to continue. There was no significant difference between the vaccine and placebo arms of the trial. There were 129 infections in the vaccinated group and 123 in those who received the placebo. The review identified no safety concerns. Trial participants are being informed of the stop and will remain in the study for follow-up.
In the halted trial, funded by MRC, the U.S. National Institute of Allergy and Infectious Diseases (NIAID), and the Bill & Melinda Gates Foundation, the “prime” was a harmless canarypox virus that carries genes for HIV’s surface protein and two of its other structural proteins. The boost contained a recombinant version of the surface protein mixed with an immune system booster, or adjuvant, called MF59.
The vaccines used in the prime-boost scheme in the South Africa study had previously been used in a study in Thailand, which produced lackluster results. In that study, which ended in 2009, HIV infections totaled 51 in the vaccine group and 74 in the placebo arm—an efficacy of 31%.
Despite this data, the researchers believed the new trial was worth the gamble, particularly given the high number of HIV infected individuals in South Africa. “The epidemic is out of control here and we have to take steps to have a biomedical intervention,” stated Glenda Gray, who heads the study and is president of the South African Medical Research Council (MRC). NIAID Director Anthony Fauci says he has no regrets about backing the study. “I don’t think it was a bad choice. It was the only choice.”
The vaccine approach in HVTN 702 is different from that being tested in other large-scale vaccine efficacy studies HVTN 705/ HPX2008 (the Imbokodo Study) and HVTN 706/HPX3002 (the Mosaico study). It is also different from the planned PrEPVacc Study, which will test yet another vaccine strategy along with oral PrEP. The stop of HVTN 702 does not affect these trials or any other HIV prevention efficacy trials taking place globally.