The Berlin Patient and the Mysterious Cure for HIV

Only one man on record has ever rid himself of the virus. New research brings the medical community one step closer to understanding how it happened.

For Timothy Ray Brown, the past two decades have been characterized by extremes of bad and good fortune, a streak of adversity giving way to a stroke of incredible, impossible luck.

In 1995, Brown, an American living in Berlin, was diagnosed with HIV.

In 2006—having kept the virus in check for 11 years with antiretroviral drugs—he was diagnosed with another life-threatening illness: acute myeloid leukemia, a cancer that attacks the bone marrow and spreads to the blood. When radiation and chemotherapy were unsuccessful, he underwent bone-marrow transplants in 2007 and 2008.

The procedures proved more successful than anyone could have expected. Today, post-transplants, he is free of cancer—and, for all intents and purposes, of HIV. (Though researchers have found genetic material from the virus in his blood, it can’t infect new cells to reproduce.) To this date, Brown, no longer on antiretroviral drugs, remains the only person on Earth to have been functionally cured of an otherwise incurable disease.

The case of the Berlin Patient, as he’s commonly known, has captivated HIV/AIDS researchers—and now, they may be one step closer to learning just how Brown’s body accomplished its seemingly impossible feat.

Scientists have long suspected that Brown’s cure is the result of some combination of three potential factors. First is the chance that when he underwent radiation for his leukemia, the treatment destroyed the majority of the infected cells in his body. A second possibility is graft-versus-host disease, a common complication of bone-marrow transplants in which the transplanted cells, interpreting the cells of their new host as foreign objects, kick the immune system into overdrive in an attack against its own body. When the recipient is unrelated to the donor, as Brown was to his, the risk of graft-versus-host is much higher; in Brown’s case, the new cells could have also killed off the virus in a happy side effect of an otherwise problematic immune response.

The third possibility is that his new lease on health had less to do with his own body and everything to do with that of his donor. In the search for a tissue match, Brown’s oncologist purposefully selected a bone-marrow donor with a genetic mutation known as delta32, found in 1 to 2 percent of northern Europeans. In most people, the CCR5 protein, a receptor found on the surface of white blood cells, is what allows the HIV virus to latch on, invade, and replicate itself; in people with delta32, the CCR5 protein is misshapen, leaving the virus useless without a host cell.

In a study published last week in the journal PLOS Pathogens, a team from Emory University winnowed down the potential factors by disproving the notion that radiation played a part. The researchers infected six rhesus monkeys with a hybrid of HIV and SIV (simian immunodeficiency virus) known as SHIV. All six monkeys received a course of antiretroviral drugs; mirroring the circumstances of Brown’s illness, three monkeys underwent radiation, which destroyed the majority of their white blood cells, followed by transplants of stem cells from their own bone marrow, which had been stored before they were infected.

When all six monkeys were subsequently taken off of their antiretroviral drugs, five of them—the three that hadn’t received transplants and two that had—saw their viral levels shoot back up almost immediately. (The sixth monkey, who had also received a transplant, was put down by the researchers after its kidneys failed.)

While not a definitive answer, the experiment does resolve one question about Brown’s treatment: The radiation for his leukemia, even though it destroyed many of his HIV-infected cells in the short term, likely had little to do with his eventual permanent cure.

But other questions still linger; with one factor out of the way, researchers are now left with the two factors that the PLOS study didn’t address. Because the monkeys received transplants from their own bodies, as opposed to donor stem cells, graft-versus-host disease is still in the running, as is the possibility that the donor’s CCR5 mutation simply left Brown’s immune system insulated against HIV. In their paper, the Emory researchers declared that bone-marrow transplant is still “a feasible intervention that can lead to a marked reduction of the virus reservoir,” though recent results have offered more setbacks than promises—the “Boston patients,” two men thought to be cured of HIV after bone-marrow transplants last year, suffered relapses a few months after going off their medications.

But still, by process of elimination, researchers are inching toward an understanding of the virus’ Achilles’ heel—and by extension, toward new treatments for an infection that currently affects around 36 million people worldwide.

Or rather, 36 million minus one. As the Berlin patient told The Seattle Times last year, “I don’t want to be the only person cured of HIV.”