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unrelated problem: acute myeloid leukemia, a blood cancer that threatened his life. Hütter, who now works at the Heidelberg Institute for Transfusion Medicine and Immunology in Mannheim, put the man on repeated rounds of chemotherapy, but after seven months, the leukemia returned. The next option was a stem-cell transplant, which would be preceded by a course of drugs to kill his immune cells–a dangerous procedure called ablation. Although the transplant would come from an immunologically matched donor, some of his own immune cells would probably remain viable, so rejection remained a risk; the physicians would try to reduce it with still other dangerous drugs. One-third of those in the man’s condition don’t survive the procedure.

When a T cell produces new copies of HIV, they burst forth, leading to the cell’s death. Antiretroviral drugs or intentionally crippled cellular receptors (a technique being tested by Cannon) prevent the new viruses from infecting healthy cells.

Although Hütter was not an HIV specialist, he knew about a mutation found in about 1 percent of people of European descent that makes their CD4 cells highly resistant to HIV. The mutation cripples a second receptor, CCR5, that the virus uses in concert with CD4 to establish an infection. If doctors could find a stem-cell donor who had this CCR5 mutation, Hütter told his patient, the transplant could theoretically enable his body to control any remaining HIV without antiretroviral drugs. “I told him we don’t know what will happen, but there might be a chance we’ll get rid of HIV,” Hütter recalls. “He said, ‘I don’t care about this–I have no problem with antiretrovirals.’ He was scared from his leukemia.”

The patient changed his mind, and in February 2007, Hütter and his colleagues performed the transplant with stems cells that had the mutant CCR5. The man then stopped his antiretrovirals. His HIV levels remained undetectable, and the doctors stopped finding evidence of latently infected cells after about two months. A year later, the leukemia recurred; he received ablation with whole-body irradiation and then a second stem-cell transplant. As of today, he remains healthy, and his HIV levels are undetectable by Hütter and his team. Even samples sent to Siliciano’s lab and other U.S. facilities that have the most sensitive assays have come up empty. Says Siliciano: “I think he’s cured.”

The results are tantalizing, but what they mean for most infected people is uncertain. As Siliciano cautions, it could be that destroying his immune cells would have cured the man no matter what replaced them. And although a CCR5 mutation stymies the most common HIV strains, some can use different co-receptors; if they are lurking inside the Berlin patient in latent form, they could one day resurface. Even Hütter says he would like to see a few more years pass with no virus before declaring the patient HIV-free. But there’s widespread agreement that he has, at least, been functionally cured. “The Berlin patient stunned the whole field, because people didn’t expect it would work that well,” says Verdin. “It’s obviously not replicable to the whole HIV population–the cost, the risk, is just incredible. But what it really shows is you can have a functional cure with no other side effects.”

Paula Cannon is betting that the immune cells with the CCR5 mutation did cure the Berlin patient. If she could use gene therapy to knock out CCR5 in a person’s own stem cells, Cannon would sidestep the thorny problems involved in finding matching donors with the mutation and then combating immune rejection after a transplant. Indeed, her interest in this strategy predates the Berlin transplant, but she says its apparent success has provided further encouragement. “I always thought CCR5 was an obvious target, and the whole thing with the Berlin patient has everyone on the same page,” she says. Cannon believes that this case was part of the reason why, last October, the California Institute for Regenerative Medicine awarded her team’s proposal more than $14.5 million. “I love the

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Credits: Daniel Hennessy, Tami Tolpa

Tagged: Biomedicine

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