The Only HIV Vaccine in Advanced Trials Has Failed. What Now?

Dozens of HIV vaccine candidates have been tested and discarded over the past few decades. The latest defeat sets progress toward a vaccine back by three to five years, experts said. Still, other options in early-stage trials may yet turn out to provide a powerful bulwark against HIV. (Getty Images)

The only vaccine against HIV still being tested in late-stage clinical trials has proved ineffective, its manufacturer announced Wednesday, another disappointment in a field long beset by failure.

Dozens of HIV vaccine candidates have been tested and discarded over the past few decades. The latest defeat sets progress toward a vaccine back by three to five years, experts said. Still, other options in early-stage trials may yet turn out to provide a powerful bulwark against HIV.

The news is “disappointing, but it isn’t the end of the effort toward developing a vaccine,” Dr. Anthony Fauci, who led the National Institute of Allergy and Infectious Diseases until December, said in an interview. “There are other strategic approaches.”

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An ongoing study called PrEPVacc in Eastern and Southern Africa is evaluating a combination of experimental HIV vaccines and preventive drugs. Scientists have made headway in developing powerful antibodies that can neutralize the virus. And they are testing new vaccine technologies, including mRNA, against HIV.

Still, the loss of the latest candidate underscores the challenges of designing a vaccine for an adversary as wily as HIV. Four decades after its discovery, the virus still infects about 1.5 million people each year, and kills about 650,000.

For people in wealthier nations, HIV is not the death sentence it once was. Powerful drugs can suppress the virus in infected individuals. There are several options available to prevent infection: Oral pills and shots given every two months are already approved in the United States, for example, and a shot that would only need to be given every six months is in late-stage trials.

But these medications must be taken for the rest of the patient’s life, and are often inaccessible to those who need them the most. A vaccine would be the ideal way to thwart the virus.

“The ultimate prevention modality for any infection, particularly viral infection, is a vaccine that’s safe and effective,” Fauci said. “That’s the reason why the field is going to continue to pursue very active research in that area.”

The trial now ending, called Mosaico, began in 2019 and was led by Janssen Pharmaceuticals, part of Johnson & Johnson. It tested the vaccine in 3,900 cisgender men (those who have always identified as male) and transgender individuals who have sex with cisgender men and transgender individuals, in more than 50 sites in nine countries in North America, South America and in Europe.

The vaccine contained a mosaic of components meant to target several different subtypes of HIV present worldwide. But the immune response it provoked against the virus did not include significant amounts of the so-called neutralizing antibodies that are considered the most powerful weapons against infection.

While the trial’s failure does not spell the end of the mosaic approach, it does signal that a successful vaccine should rouse the body to produce broadly neutralizing antibodies, Fauci said.

After reviewing early data from the trial, an independent data and safety monitoring board concluded that while the vaccine was safe, it did not prevent more HIV infections than a placebo did. The board recommended that the company stop the trial and inform the participants.

The outcome did not entirely surprise experts, because a study of the same vaccine, called Imbokodo, was halted in 2021. That trial tested the vaccine in cisgender women in five sub-Saharan African countries.

The failure of the studies is particularly disappointing partly because they were funded by Johnson & Johnson, said Mitchell Warren, executive director of the HIV prevention organization AVAC.

“Not that many companies get involved in infectious disease vaccines, so to see this not getting to market is a disappointment and a setback,” Warren said.

The news should prompt policymakers and activists to think of ways to make the existing tools for preventing HIV more widely accessible, he added: “It’s not that all hope is lost, it’s that we need to redirect our resources to greatest impact.”

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