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Wall Street Journal
Two Long-Infected Patients Seem HIV-Free After Marrow Transplants

<p>Ron Winslow</p>


July 3, 2013

-- Optimism Grows That a Cure, Once Thought Out of Reach, Is Achievable

Two patients long infected with the AIDS virus appear to be free of the virus after undergoing bone-marrow transplants and eventually stopping treatment with AIDS drugs, researchers reported Wednesday.

The patients have been off antiretroviral therapy for just 15 and eight weeks respectively, which researchers said means it is far too soon to say they have been cured of HIV, the virus that causes AIDS. But even with that caveat, the patients are among a small group of cases helping to fuel optimism among many AIDS researchers and activists that a cure for the lethal disease, once considered out of reach, is now achievable.

HIV is generally well controlled by antiretroviral medicines, but the barrier to curing patients of the virus is widely believed to be its ability to congregate in tiny reservoirs in cells where it evades treatment and stays poised to roar back when treatment is halted.

Indeed, when patients stop taking the drugs, HIV typically rebounds quickly, often within two to four weeks and almost inevitably within eight to 12, researchers said.

With the two patients, "we're starting to leave that window but we're still pretty close" to it, said Timothy Henrich an AIDS doctor and researcher at Harvard-affiliated Brigham and Women's Hospital, Boston. "It's certainly possible the virus could rebound next week or next month or even one to two years after we take them off therapy," he added. "We have to wait and see what happens."

Dr. Henrich presented details on the cases Wednesday at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur.

Immediate implications of the cases for HIV patients aren't clear. They could affect how HIV patients who need transplants for other reasons are treated, said Steven Deeks, an AIDS researcher at University of California, San Francisco who wasn't involved in the cases. But "no one would want to trade their antiretroviral drugs for a transplant," he said. "The side effects and risks of a transplant are just too great."

Among other things, Dr. Deeks and Dr. Henrich hope the findings will lead to new insights about the reservoirs and perhaps suggest new strategies for defeating them.

The new report follows the disclosure last March that a baby born in Mississippi with HIV was apparently cured with an aggressive regimen of antiretroviral drugs begun just after birth. The case was discovered after the baby's mother stopped treatment for at least five months. When the child was brought back to care, doctors found no trace of the virus.

One possible explanation is that the treatment caught the virus so early it was prevented from accumulation in the reservoirs, Dr. Deeks said.

There is growing acceptance that Timothy Brown, an American man known as the Berlin patient, represented the first known cure of AIDS, from a bone-marrow transplant he underwent in 2007 to treat leukemia. The donor was a carrier of a genetic mutation called CCR5 delta 32 that makes people highly resistant to HIV infection.

In the two new cases, the bone-marrow transplants were to treat lymphoma. Among other differences: The donors' cells didn't have the CCR5 mutation, Dr. Henrich said. And unlike Mr. Brown, who went off HIV therapy after his operation, the two recent cases both remained on the medicines long after the treatment - one patient for 4.5 years and the other for 2.9.

Doctors had been unable to detect HIV in their blood or cells for an extended period. Earlier this year, after four months of discussions with ethicists, other doctors and the patients, the decision was made to take them off therapy, Dr. Henrich said.

What has held the virus at bay so far? The fact that the patients remained on AIDS drugs during and long after the treatment likely protected the donor cells from being infected, Dr. Henrich said. Another theory is that a phenomenon called graft vs. host disease, in which the donor cells attack the patients' own cells, may have played a role.

Generally, graft vs. host disease is an unwanted side effect of transplants - complications can be lethal. But for these patients, the donor cells may have competed with and replaced the infected host cells for a beneficial effect, he said.

While some researchers say a patient should go at least two years with undetectable virus levels before being declared cured, the appropriate time is "uncharted territory," says Rowena Johnston, vice president and research director at amFAR, the Foundation for AIDS Research, a sponsor of the current research. "Even a couple of years ago I don't think we would have anticipated we would be seeing so many promising cases."

Write to Ron Winslow at ron.winslow@wsj.com



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