How did the Berlin patient become cured of HIV?

By Jon Cohen October 6

Researchers are closer to unraveling the mystery of how Timothy Ray Brown, the only human cured of HIV, defeated the virus, according to a new study. Although the work doesnt provide a definitive answer, it rules out one possible explanation.

Brown remains one of the most studied cases in the HIV epidemics history. In 2006, after living with the virus for 11 years and controlling his infection with antiretroviral drugs, he learned that he had developed acute myeloid leukemia. (The leukemia has no known relationship to HIV infection or treatment.) Chemotherapy failed, and the next year Brown received the first of two bone marrow transplants a common treatment for this cancer and ditched his antiretrovirals. (An American then living in Berlin, Brown has been known to researchers for years as the Berlin patient.

When HIV-infected people stop taking these drugs, levels of HIV typically skyrocket within weeks. Yet researchers scouring Browns blood over the past seven years have found only traces of the viral genetic material, none of which can replicate.

Today, researchers point to three factors that might independently or in combination have ridden Browns body of HIV. The first is the process of conditioning, in which doctors destroyed Browns immune system with chemotherapy and whole-body irradiation to prepare him for his bone marrow transplant.

Second, his oncologist, Gero Htter, took an extra step that he thought might not only cure the leukemia but also help rid Browns body of HIV. He found a bone marrow donor who had a rare mutation in a gene that cripples a key receptor on white blood cells that the virus uses to establish an infection.

The third possible explanation is that Browns new immune system attacked remnants of his old one that held HIV-infected cells, a process known as graft vs. host disease.

In the new study, a team led by immunologist Guido Silvestri of Emory University in Atlanta designed an unusual monkey experiment to test these possibilities.

Bone marrow transplants work because of stem cells. Modern techniques avoid actually aspirating bone marrow and instead can sift through blood and pluck out the stem cells needed for a transplant to engraft. So the researchers first drew blood from three rhesus macaque monkeys, removed stem cells and put the cells in storage. They then infected these animals and three control monkeys with a hybrid virus, known as SHIV, that contains parts of the simian and human AIDS viruses. All six animals soon began receiving antiretroviral drugs, and SHIV levels in the blood quickly dropped below the level of detection on standard tests, as expected.

A few months later, the three monkeys with stored stem cells underwent whole-body irradiation to condition their bodies and then had their own stem cells reinfused. After the cells engrafted, a process that took a few more months, the researchers stopped antiretrovirals in the three animals and in the three controls. SHIV quickly came screaming back in the three controls and two of the transplanted animals. (One of the transplanted monkeys did not have the virus rebound, but its kidneys failed and the researchers euthanized it.)

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How did the Berlin patient become cured of HIV?