PrEPVacc, the last of several large HIV vaccine studies, was halted ahead of schedule in early December after an interim review showed that there was little or no chance of the trial demonstrating vaccine efficacy.

Only one large vaccine study—the RV144 trial in Thailand—has shown any effectiveness for HIV prevention. That trial tested a vaccine (AIDSVAX) containing HIV’s gp120 envelope protein plus a second vaccine that delivered DNA instructions for HIV proteins. In 2009, researchers reported that this regimen reduced new infections by 31%.

The PrEPVacc trial, which enrolled more than 1,500 men and women in Africa, used a similar approach. Participants were randomly assigned to receive AIDSVAX plus a DNA vaccine, a three-vaccine regimen or placebo injections. In addition, the study compared two PrEP pills; the oral PrEP component will continue.

As of October, more than 1,000 participants had received the full vaccine regimen, and most also received one of the PrEP pills. The study’s independent data monitoring committee found no safety concerns but determined that the trial probably would be unable to show whether the vaccine prevents HIV. This is not surprising: PrEP pills alone are highly effective, making it challenging to show that a vaccine offers additional protection.

“We have come so far in our HIV prevention journey, but we must look to a new generation of vaccine approaches and technology to take us forward again,” says PrEPVacc chief investigator Pontiano Kaleebu, MD, PhD.