The four-decade effort to create an HIV vaccine took a major blow last week with news that Janssen Pharmaceuticals, a division of Johnson & Johnson, was shutting down the only late-stage clinical trial of a vaccine. The results have shown that it is ineffective.
“I was disappointed with the outcome,” says Mitchell Warren, executive director of AVAC, an organization advocating for HIV prevention to end AIDS. “It was a setback in the search for a vaccine.” So it’s back to the drawing board with several initial small-scale clinical trials underway and more that could eventually enter the research pipeline.
Since 1982, when the US Centers for Disease Control first named the syndrome “AIDS,” there have been years of fear and death that have given way to astonishing scientific advances in understanding and treating AIDS.
But the holy grail has always been finding a vaccine that would stop people from becoming infected with HIV.
“The only way we’ve ever actually eradicated a disease [in humans]and that was smallpox, it’s with a vaccine,” says Dr. Susan Buchbinder, director of HIV prevention research at the San Francisco Department of Public Health and a professor at the University of California, San Francisco.
Medical advances in AIDS include antiretroviral drugs (ARTs) to suppress the virus and keep the disease under control; and pre-exposure prophylaxis (PrEP) drugs to prevent HIV transmission when taken correctly by uninfected people who see themselves at risk. Today, nearly 29 million of the world’s 38 million HIV-infected people have access to lifesaving antiretroviral drugs, according to UNAIDS.
But access to PrEP drugs has been much slower, and in 2020, according to the World Health Organization, 97 percent of the 940,000 PrEP users worldwide lived in just 30 countries.
And an HIV vaccine remains frustratingly out of reach. This contrasts with less than a year spent developing COVID-19 vaccines that prevent serious illness, hospitalization and death in most cases.
So if scientists can do it so quickly for COVID-19, why can’t they come up with a vaccine to prevent HIV?
A large part of the reason, Warren says, is the speed at which the AIDS virus mutates. “The world has been tracking variants of COVID,” he says. Such variants include Alpha, Beta, Delta, Omicron and subvariants. But HIV is much more variable. “There are more variants of HIV in a person’s body within days of infection than all variants of COVID.” This means that even if a vaccine is being developed to attack HIV, the virus could mutate out of its reach.
A vaccine’s job is to teach the immune system to recognize the disease and create antibodies to fight it. It hasn’t worked with HIV so far.
“AIDS integrates itself into the immune system. It mutates incredibly rapidly, making it a moving target for the immune system,” says Dr. Bruce Walker, director of the Ragon Institute at MGH, MIT and Harvard, which brings together scientists and engineers to better understand the immune system. “Meanwhile, the immune system is being destroyed by the virus itself.”
Another factor that has aided the rapid development of a COVID-19 vaccine, one not seen in HIV, is that the body’s immune system, alone, helps most patients recover. Of the 663.6 million people worldwide who had confirmed cases of COVID-19, 6.7 million have died since the start of the pandemic, according to WHO. Even before vaccines were available, most people recovered from COVID-19. The vaccines improved their chances of not being infected or recovering if infected. “Our current [COVID-19] vaccines teach the body’s immune system to do what it does naturally, get rid of the virus, only faster,” says Warren.
“But nobody eliminates AIDS naturally,” he says. “With HIV, we’re trying to create a vaccine to do something that nature doesn’t do by itself.” People don’t get over HIV infection the way they get over the flu or even COVID-19.
Instead, they live with HIV, thanks to new drugs that reduce the viral load to undetectable levels. And PrEP drugs, when taken correctly by uninfected people, can prevent new infections.
Isn’t that enough, even without a vaccine? Why continue the search for the holy grail of AIDS if PrEP can stop the spread of the disease?
“The reality is, yes, we still need a vaccine,” Walker says. “In parts of the world where AIDS is even more prevalent, PrEP is not always available.” While the cost of PrEP has dropped in most low-income countries to less than $100 a year, it can be difficult for those in remote areas to access the drugs, and the lingering AIDS stigma can make people reluctant to take the pills. For others, it may be difficult or impossible to stick to the daily regimen of pills, or the injection every two months, which is necessary for the drug to be effective. “Theoretically, if everyone had access to PrEP and everyone took it religiously, we might not need a vaccine. But humans aren’t perfect.”
While Johnson & Johnson’s HIV vaccine failure was disappointing, no one is giving up. “You can’t work in HIV if you don’t maintain a certain optimism,” Warren says.
There are glimmers of hope. In March, for example, the National Institutes of Health launched an initial small trial of three experimental HIV vaccines using new messenger RNA (mRNA) technology, which has been used in the development of Pfizer and Moderna COVID-19 vaccines. 19.
Buchbinder says the HIV Vaccine Trials Network, an international collaboration focused on evaluating vaccines to prevent transmission of the virus, has “a whole portfolio of vaccine trials to test.” They are small initial studies, not yet close to determining whether they are effective at halting HIV transmission in large numbers of people. But “we learned a lot from each [HIV vaccine] process,” he says. “I’m hopeful.”
Susan Brink is a freelance writer covering health and medicine. She is the author of The fourth quarter and co-author of A change of heart.