AIDS: 2nd Remission in History Reignites Doctors' Hope for a Cure for HIV
“That’s the six million dollar question."
This week, scientists in England proclaimed the “London patient” to be the second person to ever go into long-term HIV remission. For the 36.9 million people who suffer from HIV worldwide, the news was a bright glimmer of hope. It was a landmark moment in the quest for an HIV cure that raises an important question: can the “London patient” treatment also help everyone else with HIV?
Only one other person has gone into remission after receiving this treatment: the “Berlin patient,” who did so in 2008. The London patient is his only successor, though a “Dusseldorf patient” may soon be confirmed as the third. All three are said to be in “long-term remission,” not “cured” per se; right now, it’s still too early to tell.
All three of these patients received bone marrow tissue donations from donors who had a very specific genetic mutation called CCR5 delta 32. The mutation makes it impossible for the HIV-1 virus to latch onto immune cells, making them resistant.
The CCR5 mutation is the same one involved in the experiments of rogue Chinese scientist He Jiankui, who attempted to genetically engineer twin girls to be HIV resistant. While such ethically fraught experiments are out of the question, the CCR5 mutation highlights the promise of gene therapy to cure at least one strain of HIV.
“Gene therapy tried to mimic the Berlin patient over ten years ago without success,” Gero Hütter Ph.D., the hematologist who led the Berlin patient experiment, tells Inverse. “However, techniques are improving. The new patient will probably push gene therapy approaches again.”
What We Learned From Berlin, London, and Dusseldorf
Gene therapy is perhaps one of the most promising roads to an actual cure for HIV, USC Keck School of Medicine microbiology and immunology professor Paula Cannon, Ph.D., tells Inverse. The trick, however, is figuring out how to use that CCR5 gene safely, ethically, and effectively.
"That’s really the the six-million-dollar question.
“That’s really the the six-million-dollar question,” Cannon tells Inverse. “Of course, as gene therapists, we’re excited to see what are the essential component in that treatment that led to these cures and see if we can recapitulate them.”
What we see in the London and Berlin patients, says Cannon, is the result of a two-step process that resulted in HIV remission. Both of them had HIV but they also had leukemia, a cancer that infects bone marrow cells — which, crucially, produce immune cells. They both underwent aggressive chemotherapy intended to kill off the cancer cells that infected their bodies. It took out a great deal of their HIV-infected immune cells, but it also gutted their immune systems.
“Those drugs are also poisonous to other cells in the body, and especially the bone marrow stem cells that are needed to produce new blood and immune cells for you,” Cannon explains. “The problem with chemotherapy at doses you’re given for these cancers is, sure, they’ll cure you of your cancer, but a few weeks later you’ll die because you no won’t have a functioning immune system because it’s being hacked out.”
"I am very happy that it worked so well.
To replace those cells, the patients needed a bone marrow donor who was a tissue match. In these cases, however, the donor also happened to have the CCR5 mutation. So when the donated bone marrow stem cells started to rebuild the patients’ devastated immune systems, the new cells carried the CCR5 mutation. As such, they couldn’t host the HIV virus — and as a result, the levels of virus in their system plummeted.
Their HIV levels didn’t drop to zero, but they decreased significantly enough for patients to stop taking the antiretroviral therapy drugs that patients with HIV must take every day to control the infection.
Hütter says that these patients show us that CCR5 mutation really does work to combat HIV. “I am very happy that it worked so well,” he says of the London patient. “I think the second patient is at least as important as the first one because it confirms the principal idea of CCR5 withdraw in HIV patients.”
The problem is that gutting the immune system with chemotherapy is far from feasible for a gene therapy-based HIV cure. For one thing, bone marrow transplants are emergency procedures. What scientists must figure out is whether they can simply introduce cells genetically engineered with the CCR5 mutation into a patient’s body or whether they must destroy the HIV-infected immune cells first.
If simply introducing the gene will do the trick, genome-editing techniques like CRISPR make it a powerful option. But if aggressive immune system disruption is necessary, it may stop this therapy in its tracks.
“If it turns out that making somebody’s cells CCR5-negative alone is not sufficient then that’s a problem,” Cannon says. “Giving people drugs that attacks immune cells, especially at the levels that these cancer patents are getting is a dangerous thing to do, it wouldn’t be justified because somebody had HIV.”
How Feasible is a Gene Therapy Cure for HIV?
Whether gene therapy could lead to a scalable cure for HIV will greatly depend on whether immune system destruction is necessary for it to work.
But even if it turns out that it is necessary, Cannon says that gene therapy could still be an effective way of managing HIV infection.
“There are clinical trials ongoing where patients’ own cells are taken out, made CCR5 negative and then popped back in,” she says. “If those patients are able to cure themselves, or able to control the virus, you might get a situation where they aren’t completely cured of HIV but their newly engineered CCR5 immune system is able to kind of keep a lid on everything.”
Importantly, there are drugs that already help patients control their HIV in this way. The aforementioned retroviral drugs help control the infection, and those at risk for HIV can take a daily, preventative dose of drugs. This technique is called pre-exposure prophylaxis (PrEP) and can reduce the risk of sexual HIV acquisition by 90 percent. In the United States, there is a public health proposal to get these drugs to people who are at risk, and in that way, stop the spread of the virus.
"We can do better.
Cannon adds that a successful gene therapy approach would perhaps reduce the need for a daily dose of drugs for HIV patients — not an insignificant factor, considering many HIV patients already face stigma and discrimination due to their condition.
But stopping the spread or controlling a condition is different from actually finding a lasting cure. Maybe what these three cases can really do is reignite efforts to answer the important questions about immune cell destruction that will decide whether CCR5 really is that cure. Hütter and Cannon both seem to believe that this is possible.
“We can do better,” Cannon says. “We understand that there is a reason to be aiming and aspiring for these treatments. When we get them — and we will because we’re human beings, and we’re smart and can figure things out — I think this would be an attractive possibility for many people.”