Thursday, December 13, 2012

Berlin Patient, first person cured of HIV, may soon have company

Berlin Patient, first person cured of HIV, may soon have company

July 27, 2012|By Erin Loury | Los Angeles Times

  • Timothy Brown, a.k.a. the Berlin Patient, is the only person considered cured of HIV, but others may join those ranks soon.
Timothy Brown, a.k.a. the Berlin Patient, is the only person considered… (EPA/MICHAEL REYNOLDS )
Washington, D.C. — The Berlin Patient, the only person considered cured of HIV, may soon have some company.
Researchers at the International AIDS Conference in Washington, D.C., made presentations Thursday on two HIV-positive men from Boston who developed lymphoma. In both cases, their treatment included a bone marrow transplant, which results in a new immune system. The bone marrow donors did not have HIV.

The patients were conditioned for their transplants with a reduced-intensity protocol that allowed them to maintain enough strength to continue taking antiretroviral drugs to keep their HIV in check. These drugs are usually too toxic for HIV-positive cancer patients to handle.
So far, it appears that their new immune systems have remained HIV-free. Seventeen months after the transplants, researchers could not detect any HIV genetic material in the patients’ blood. They say the credit for this goes to the antiretroviral drugs the patients are taking.
Still unclear is whether the virus still lurks in the patients’ tissues. “It is possible that there is still other residual HIV material, “said study author Dr. Timothy Henrich of Harvard University and Brigham and Women's Hospital. If doctors became convinced that all trace of the virus is gone, the patients could stop taking the antiretroviral drugs and be considered cured.
But they’re not there yet.
“We’re being very carful to refer to our patients as not being functionally cured,” said study author Daniel Kuritzkes, also of Harvard University and Brigham and Women's Hospital. Only when these patients can successfully stop their medication can they be considered cured of HIV.
The only person in that category right now is the Berlin Patient, a.k.a. Timothy Brown. He had a bone marrow transplant to treat acute myeloid leukemia. In his case, the bone marrow donor was not only HIV-negative, but had a rare genetic mutation that blocks HIV from entering cells. That effectively makes Brown immune to the virus, and his body has remained HIV-free even without taking antiretroviral drugs.
The two patients in Boston received their bone marrow transplants from people who did not have the rare genetic variant, which is why they are still taking their drugs.
Researchers are working on potential cures that involve transferring that genetic mutation to HIV-positive patients without taking on the significant risks of a bone marrow transplant.
Another study presented Thursday reported on 12 French HIV-positive patients who received early treatment and have acquired an ability to naturally control HIV.  These patients offer hope that it may be possible to “functionally” cure the disease – enabling people to tolerate HIV without completing ridding their bodies of the virus.
The patients started taking antiretroviral medication within 10 weeks of their HIV infections and stopped about three years later.  Now, nearly seven years after ending treatment, these patients still have very low levels of the virus in their bodies. They appear similar to a small group of people known as “elite controllers” who naturally suppress HIV to low levels and do not get sick from the virus.
Reservoirs of dormant HIV can occur throughout the body. This sleeping HIV can periodically wake up and re-infect a person, which is why people with HIV usually have to take medication for life.

The French patients still have very low reservoirs of virus in their bodies, and researchers wondered if their ability to manage the virus related to how these remaining patches of HIV were distributed among a type of white blood cells called memory T cells. Pockets of HIV usually build up in long-lived types of memory T cells. However, researchers found that this rare cohort had dormant HIV primarily in shorter-lived memory T cells – similar to elite controllers – so their infected cells don’t persist as long.
The results provide further evidence that antiretroviral therapy should be started soon after infection, researchers said.
To wipe out all traces of HIV, scientists must find a way to wake up reservoirs of sleeping virus and target them with drugs. Jerome Zack, director of the UCLA Center for AIDS Research, made a presentation about this approach.
Zack and his colleagues outfitted little lipid bubbles called liposomes with antibodies that specifically match up with CD4 cells, the type of white blood cell that HIV usually attacks. The liposomes deliver two drugs to the cell – one, called bryostatin, switches on cell activity, and the other, a protease inhibitor, prevents HIV virus from assembling more virus once it starts to reproduce.
These liposomes didn’t target or otherwise activate another type of white blood cells called CD8 cells. As a result, the treatment didn’t trigger toxic inflammation. However, scientists still need to figure out how to design liposomes that identify only the CD4 cells that are infected with dormant HIV.
Bryostatin is a useful molecule, but also exorbitantly expensive – a single gram can cost $1 million.
Zack and his colleagues published a paper in Nature Medicine last week that described a number of synthetic products that mimic bryostatin, and cost only about $2,000 per gram to manufacture. Zack said that a few of these compounds also outperform their natural counterpart in switching on latent HIV while triggering less inflammation.

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