Paul Volberding is a UCSF oncologist who treated San Francisco’s first HIV patients in the early 1980s.
“The patients were, in many cases, blind and demented and had cancer and had infections in their brains causing pressure and headaches,” says Volberding. “People now can’t imagine it, it was so bad.”
Volberding says for years, HIV infection was a rapid death sentence. But in the 35 years since the epidemic began—thanks to sophisticated anti-retrovirals—it’s become a chronic illness that people can live with for decades.
Today, on the eve of World AIDS Day, UCSF is scheduled to announce that it’s receiving a $20 million grant to find a cure for AIDS over the next five years. It’s part of a $100 million effort by the American Foundation for AIDS Research or amfAR, to fund the most promising research that could lead to curing AIDS.
Not long ago this might have sounded unbelievable.
“I think it would have felt a lot like a moonshot, maybe five or six years ago,” Volberding says.
But today, Volberding’s lab and others in San Francisco are working for that moonshot: to develop treatments over the next several years that can drive the viral load down low enough that the body’s own immune system can control or eliminate it.
“If it can be done anywhere, it can be done here,” he says. “It’s a really exciting moment.”
The Problem With Treatment
The U.S. Food and Drug Administration approved zidovudine or AZT in 1987; it was the first antiretroviral medication to treat HIV.
By 1996, drug “cocktails” to treat HIV became the standard of care for most patients. These highly active anti-retroviral therapies (HAART) helped manage the patient’s viral load, maintained function of the immune system and prevented infections that could become fatal.
After HAART became widespread, the Centers for Disease Control and Prevention reported a marked reduction in HIV-related deaths.
But these medications have side effects.
“Antiretrovirals are not a panacea,” says amfAR CEO Kevin Robert Frost, who’s based at the organization’s headquarters in New York.
Frost says the drugs have side effects that include chronic inflammation and a range of infections that attack the weakened immune system.
That’s why amfAR is spending $100 million to find a cure for the nearly 37 million people living with HIV around the world.
“The only real way out of an epidemic like this is through a cure and a vaccine,” says Frost. “Because we’re gonna have to cure the people who have it now and we’re gonna have to vaccinate those to prevent them from getting it in the future.”
‘Shock and Kill’ the Virus
Like many HIV patients, TJ Lee is active and pain-free.
“Once you get on meds and take care of yourself, you can live a very normal life,” says Lee, who has been HIV-positive for 16 years.
The San Francisco resident takes just one pill a day to manage his HIV. As a program manager at the San Francisco AIDS Foundation he works with newly diagnosed people who don’t know HIV is no longer a death sentence.
“I had somebody call me about a month ago,” Lee says. “He recently found out he had HIV and he thought he was going to die soon.”
For people who have access to treatment, that’s not really a concern anymore.
However, even people who are free of symptoms can have HIV lying dormant in their body’s T cells for years. The inactive virus could one day become active and reproduce.
Eliminating that latent virus is the focus of UCSF’s research. With the $20 million amfAR grant, Volberding wants to target these viral cells with a method he calls shock and kill.
“If the virus is dormant, we first need to wake up that cell to start producing the virus, that’s the shock part of it,” Volberding says. “And then, once the virus has been activated we want to do something to help the body kill off those cells, to get rid of the virus.”
Researchers have to wake up the virus because when it’s dormant, the infected cell is invisible to the immune system. By shocking it out of latency, scientists can kill the infected cells, and kill the virus as it reproduces.
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This method could be an answer, Frost says, not the answer. Researchers are working on multiple ways of reducing the body’s viral load, including rapid early treatment to abort the infection and gene therapy to engineer cells to make them resistant to infection. Plus, public health efforts aimed at prevention and treatment will continue to be important, especially in places like sub-Saharan Africa, where 28.5 million people are infected with HIV.
“I don’t think we’re gonna wake up one day and see a headline in the newspaper that says ‘Cure for AIDS Found,’” Frost says. “It’s not that kind of a disease, it’s much more complicated than that.”
Because HIV mutates so quickly, he adds, a cure is likely to come in stages—sort of like a cancer model where a patient goes into remission.
Remission would mean a point where the patient doesn’t need treatment, can’t infect anyone, and doesn’t have chronic illnesses.
“We’re likely to start out curing some of the people some of the time, then more of the people more of the time,” he says, “and hopefully get to a place where we cure most of the people most of the time, and everybody who needs it has access to it.”
Frost says eliminating the virus will take not one, but a series of scientific breakthroughs, as researchers work on all fronts from latency to gene editing and gene therapy.
“There are those who said space travel would never happen,” says Frost. “People who say a cure for AIDS is impossible simply don’t understand the science. We’re going to find a cure for AIDS; I can tell you that without the slightest hesitation or doubt in my mind.”