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Stem cell transplants and HIV

March 5, 2019

An HIV-positive man in the UK has been cleared of the AIDS-causing virus after a stem cell transplant. Experts welcome the development, but warn the risky procedure can't help the millions of people infected with HIV.

The HIV/AIDS virus
Image: picture-alliance/Photoshot/B. Coleman

A man known only as the "London patient" has become the second known adult to be free of the AIDS virus following a bone marrow transplant, doctors said Tuesday.

The journal Nature reported that he underwent the procedure in 2016 to treat a type of blood cancer called Hodgkin's Lymphoma. The stem cells he received came from a donor with a rare genetic mutation that resists most HIV strains. 

Doctors say he's in sustained remission and has shown no sign of the virus for 18 months.

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How does the treatment work?

  • Stem cell — or bone marrow — transplants aim to replace unhealthy blood-forming cells with healthy ones.
  • The procedure allows doctors to blast blood cancer in the bone marrow with large doses of radiation therapy or chemotherapy.
  • A donor's stem cells are then transfused into the patient's blood to reprogram the immune system and restore normal blood cell production.
  • In the case of the "London patient" and Timothy Brown — the only other adult to be declared HIV-free  the cells came from a donor with a rare mutation of the CCR5 protein.
  • Most HIV strains use CCR5 receptors to enter immune cells in the body. But if the transplanted cells are mutated and resist HIV, the virus can't get in.
  • This doesn't apply to the X4 form of HIV, which uses the CXCR4 protein to enter cells.

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Possible risks and side effects

While the remission of the "London patient" is being celebrated, such transplants are unlikely to be adopted as a routine treatment option for people infected with HIV.

That's because the procedure is dangerous, costly and is intended only as a last-stage therapy for patients with life-threatening diseases. Currently, people infected with HIV can keep the virus in check and live relatively normal lives for many years  by taking antiretroviral drugs.

Stem cell transplants, on the other hand, are highly invasive and can result in complications or side effects that can persist for years afterwards. 

Two cases of success

The "London patient" is only the second known person to have been cleared of HIV via this method. The first, Timothy Brown, 52, was declared cured in 2008 after having bone marrow transplants for leukemia. Brown almost died during the treatment, with his immune system left severely battered. He suffered graft-versus-host disease — when the donor immune cells attack the recipient's immune cells — and at one point had to be placed in an induced coma.

The "London patient" suffered fewer harmful effects, although he also had mild graft-versus-host disease in the gut. 

Scientists had long been trying to replicate the success achieved with Brown 10 years ago. Following most attempts, the viruses rebounded after just a few months, or patients died from the cancer.

Navneet Majhail, director of the Blood & Marrow Transplant Program at the Cleveland Clinic in Ohio, pointed out on Twitter that finding a donor can also be a huge challenge. Just 1 percent of people descended from northern Europeans have the HIV-resistant mutation. It is rarer still in other populations.

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How has the news been received? 

Experts say the outcome of the stem cell treatment offers hope for a future cure for HIV/AIDS, but many have also questioned its relevance for the millions of people already infected.

Anton Pozniak, president of the International AIDS Society, said it represented a "critical moment."

"The hope is that this will eventually lead to a safe, cost-effective and easy strategy ... using gene technology or antibody techniques," he said.

Matthew Hodson, director of NAM aidsmap, an organization that provides information to support people living with HIV, said: "It would be unwise to think that we are on the brink of curing HIV when, after two decades (of having the medical resources to treat HIV) we have still not been able to provide treatment for all."

Thurka Sangaramoorthy, associate professor at the University of Maryland, whose work focuses on HIV/AIDS, called for focus, money and resources not to be shifted away from those living with HIV around the world.

"This is not a treatment appropriate for people with HIV who do not have cancer," the US-based Treatment Action Group said in a statement. "The hope is that lessons can be learned to help develop more widely applicable therapeutic approaches for attaining HIV remissions or cures."

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Where to from here?

Scientists at IciStem — a consortium of European scientists studying stem cell transplants to treat HIV infection — are currently tracking 39 HIV-infected patients who have received bone-marrow transplants. One is a patient from Düsseldorf, in western Germany, who has been HIV-free for almost 4 months.

Ravindra Gupta of the University of Cambridge and the lead author of the Nature study, told the AFP news agency that if the goal is to get people off antiretroviral drugs and into remission, "then targeting CCR5 therapeutically is an option that we need to explore further."

Several research studies are underway to develop gene therapy treatments. For example, scientists are working to mutate the CCR5 receptors that HIV uses to enter cells in the hope of creating an immune system the virus can't infect. Clinical trials are also underway in the US to test the possibility of modifying blood stem cells from an HIV-infected person to make them resistant to the virus, before re-introducing them to the patient.  

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