In another blow to the decades-long quest for an HIV vaccine, researchers are pulling the plug on the largest ongoing clinical trial after a review in January found the experimental injections provided no protection from the virus that causes AIDS.

The $120 million study, conducted by the HIV Vaccine Trials Network (HVTN) based at Seattle’s Fred Hutchinson Cancer Research Center, was launched more than three years ago and involved 5,407 volunteers in South Africa.

“There was great hope and expectations around this vaccine candidate,” said Mitchell Warren, executive director of AVAC, a global HIV prevention organization that has been promoting vaccine development for 25 years. “It’s incredibly disappointing.”

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The trial in South Africa was considered especially promising because it was based on a vaccine tested in Thailand that was the first to show even the slightest effectiveness. Scientists tweaked the Thai vaccine to increase its potency and target the strain of HIV most common in South Africa. They also added booster shots to the regimen in hopes of inducing long-lasting immunity.

Initial results showed the vaccine triggered a strong immune response. But when an independent monitoring board analyzed the outcomes last month, they found 129 new HIV infections among people receiving the vaccine compared with 123 among those who got a placebo. The difference between the two groups wasn’t statistically significant, and there’s no evidence the vaccine raised the risk, said Dr. Larry Corey, former president of Fred Hutch and principal investigator for the HVTN. It just wasn’t effective in preventing infection.

“We’ll learn from this, but we need to press on,” Corey said. “This epidemic is continuing at amazing rates in South Africa and probably the rest of sub-Saharan Africa.”

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AIDS deaths have dropped sharply around the world since the introduction of antiretroviral drugs that keep HIV in check and reduce transmission — but there is still no cure. About 1.7 million people were newly infected in 2018. The highest levels were in Eastern and Southern Africa, where a third of people with the virus aren’t getting the drugs. In South Africa, nearly one in five young and middle-aged adults are living with HIV.

Scientists say a vaccine is the only practical way to shut down transmission and eventually eliminate the virus, which has killed more than 32 million people since the first cases in the U.S. surfaced in the early 1980s.

“An HIV vaccine is essential to end the global pandemic, and we hoped this vaccine would work,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease (NIAID), said in a statement. “Regrettably, it does not.” NIAID and The Bill & Melinda Gates Foundation shared equally in the cost of the project, with the South African Medical Research Council providing facilities and personnel.

The findings are the latest in a long string of disappointments for HIV vaccine research. More than 100 vaccines have been tested in people with little to show for it. One trial was halted in 2007 because the vaccine actually made people more vulnerable to infection. Until the Thai vaccine trial in 2003, which reported a modest, 31 percent protection level, some experts questioned whether it would ever be possible to craft a vaccine against the insidious, rapidly-mutating Human Immunodeficiency Virus.

“We know it is possible, but we also know HIV is the most challenging virus for which we’ve ever tried to create a vaccine,” Warren said.

The study participants, aged 18 to 35 years old, are being notified of the results. They will not receive any additional doses of the vaccine, but researchers will track them for another year and continue to provide HIV prevention counseling and protective antiretroviral drugs.

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Several other experimental vaccines, which take different approaches to tackling the virus, are still being tested in trials overseen by the Fred Hutch group. One uses a combination, or mosaic, of genes from many different strains of HIV, with the goal of triggering a broad immune response that might protect against all of them.

Another takes an entirely different tack, building on the fact that about 10% to 12% of people infected with HIV produce what are called “broadly neutralizing antibodies.” These antibodies can kill many different strains of the virus, but the response is slow and not powerful enough to cure the disease. Scientists think it might be possible, though, to prevent infection by directly infusing people with the antibodies.

“The good news is that there are multiple efforts going on right now,” Warren said. “It’s certainly not as if we don’t know what to do next.”