The PREP vaccine trial testing two experimental HIV prevention regimens in Africa has been stopped after investigators announced that there is "little to no chance" the trial will show the vaccines are effective.
This phase 2b trial was the last attempt in this generation of vaccine development, which has used non-neutralizing antibodies, experts say, and scientists will have to begin anew.
"We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere," International AIDS Society (IAS) Executive Director Birgit Poniatowski said in a statement.
The African-led, European-supported HIV prevention study has been running since 2018 at four sites in Uganda, Tanzania, and South Africa and has involved 1513 participants aged 18-40 years. The vaccine trial was testing two experimental combination regimens designed to protect against HIV and a new form of pre-exposure prophylaxis. The PREP trial will continue.
Almost 21 million of the 39 million people in the world with AIDS live in the test-site region of eastern and southern Africa, according to the IAS.
The news isn't a huge surprise, as the last two HIV studies testing non-neutralizing antibodies showed a lack of efficacy, Larry Corey, MD, virologist and principal investigator of HIV Vaccine Trials Network, headquartered in Seattle, told Medscape Medical News.
But the results of this trial may help answer a question. "There is a small group of people who have really high immune responses to a part of the virus we call the V1V2 loop," he explained. "But the frequency of people with that immune response is only 8%-10% of the population. If this trial, using a different vector, shows the same thing, then we have to spend a lot more time making an immunogen that gets 100% of the people to the levels of immunity that might be correlated with the V1V2 loop, and we'd walk out of this with a really good insight as to what to do next."
So far, he said, scientists working to develop a vaccine haven't determined which part of the virus to target.
"The clinical trial was very well done, and that's the success," Corey said. But "are we going to learn from it?"
The lack of an HIV vaccine continues to frustrate patients and scientists, especially because vaccines for other diseases, such as COVID-19, have been developed at record speed. But COVID-19 presented a completely different challenge for vaccine development, he explains.
"We're doing something much harder with HIV than we did with COVID," he said. "COVID vaccines prevent you from getting sick; you still get infected. With HIV, you have to prevent someone from getting infected in the first place. And that requires way more antibody and a way better immune response."
Although there are other prevention tools for HIV, a vaccine is the only way to meet global elimination goals, he noted, pointing out that people who are at the highest risk for HIV "have an unchanged incidence over the past 15 years of 4% a year."
"We are nowhere close to ending the HIV epidemic," Corey said. "We're not going to meet the 2030 goal. And one of the reasons we're not going to meet the 2030 goal is that between 40% and 50% of the cases of HIV globally are in people who don't self-identify as high risk."
That's the limitation with PREP, which has been available for nearly two decades. It counts on the acceptance, intake, and adherence of people at a high risk for HIV. "That has been abysmal with oral PREP," he said.
There are long-acting antiretrovirals or long-acting monoclonal antibodies. But from a cost and effort standpoint, those would also be focused on people who consider themselves high risk, he pointed out. "In some countries, you could make a case that everybody's high risk."
The only way we've really ever controlled a disease on a population base is with a vaccine, he said. "Just because it's hard, doesn't mean you give up. All the data say you've got to have it."