Meanwhile, advances in treatment have further shifted attention from the hunt for a cure. A study released in May found that early anti-retroviral therapy decreases patients’ infectiousness by a striking 96 percent. Today, most people on anti-retroviral drugs achieve an undetectable viral load—there is virtually no HIV circulating in their blood. An idea has taken hold: We can live with this.
But we cannot. Doctors will tell you that many patients still fail treatment and die. As people age with the disease, we are seeing that even those successfully treated can lose years of life. A massive multicountry study published in The Lancet in 2008 reported that someone starting therapy at age 20 could expect to live to only 63. The following year, another study found that a group of HIV-positive patients with a median age of 56 had immune systems comparable to those of healthy 88-year-olds. The latent reservoir of HIV seems to be most to blame, producing inflammation that degrades the immune system, increasing susceptibility to age-related diseases. What’s more, research has shown that the drugs themselves can lead to increased risk of heart disease, diabetes, and osteoporosis.
The cost of treatment is also unsustainable. In the United States, second-line drugs—for people who don’t improve on standard medications—can total $30,000 a year. Cash-strapped states are trimming programs that pay for these medicines; there are now more than 8,300 people in America on waiting lists for anti-retroviral drugs. In developing countries, drugs are much cheaper—some generic regimens cost only $67 annually—but wealthy nations are wearying of picking up the bill. According to UNAIDS, 10 million people in the Third World who need treatment are not getting it at all. The math of the epidemic is unrelenting: For every three people who start treatment, five new people are infected.
A vaccine for AIDS is “probably decades away,” says Daria Hazuda, a vice-president at Merck. “There’s still an enormous amount of hope, but people now realize it’s going to be extremely complicated.” We know now that we will neither treat nor vaccinate our way out of this epidemic. But there could be another way for it to end.
In February 2007, Brown had his stem-cell transplant from Donor 61. Right before the procedure, he stopped taking his anti-retrovirals. He survived the operation—no small feat, since stem-cell transplants from unrelated donors kill a hefty minority of the people who undergo them. His initial recovery was encouraging. “I went back to work, started working out at a gym and riding my bicycle again,” he says.
Then Brown relapsed. In February 2008, Hütter did another transplant from Donor 61. (Going back to the same donor is standard; the patient is now accustomed to that immune system.) This time, the cancer seems to have stayed away. More striking: More than four years after he stopped taking anti-retroviral therapy, there is also no sign of HIV in his body. Brown is now surely one of the most biopsied humans on Earth. Samples from his blood, his brain, his liver, his rectum, have been tested over and over. People in whom the disease is controlled with anti-retroviral therapy will still have hidden HIV—perhaps a million copies. But with Brown, even the most sensitive tests detect no virus at all. Even if trace amounts remain (it is impossible to test every cell), it no longer matters. Absent the CCR5 receptors, any HIV still present cannot take root. He is cured.
A stem-cell transplant from an unrelated donor can cost $250,000 and is a reasonable risk only in the face of imminent death. What cured Timothy Brown is obviously not a cure for the rest of the world. But it is proof of concept, and it has jolted AIDS-cure research back to life. Sometimes science follows sentiment; the abandonment of cure research after the disillusion of the nineties is now playing out in reverse.
For Brown’s cure to be relevant on a wide scale, it would have to be possible to create the delta 32 mutation without a donor and without a transplant—preferably in the form of a single injection. As it happens, progress toward that goal has already begun, in the laboratory of Paula Cannon at the University of Southern California. Instead of a donor, Cannon is using a new form of gene editing known as zinc finger nucleases, developed by the California company Sangamo BioSciences. Zinc finger nucleases are synthetic proteins that act as genetic scissors. They can target and snip a specific part of the genetic blueprint: They can, for instance, cut out the code that produces the CCR5 receptor, yielding a cell with HIV resistance.
Cannon works with mice given human immune systems, since normal mice cannot get HIV. In one study, she took human stem cells, treated them to have the CCR5 mutation, and injected them into a group of mice, with another set of animals given untreated stem cells as a control. Then she infected both groups with HIV. The result, as published in Nature Biotechnology in July 2010: The control group got sick and died. The mice given the mutation fought off the virus and remained healthy.