Second HIV Patient in Remission after Stem Cell Transplant

By Ann Miller Baker - March 15, 2019

It’s a genetic mutation that’s been around for thousands of years, presumably helping the Vikings to avoid infections like the bubonic plague and smallpox.

Now, it’s popped up in news stories about an HIV-positive blood cancer patient who was seemingly cured of both diseases through a hematopoietic stem cell transplant (HCT).

The mutation, in a gene called CCR5, prevents the human immunodeficiency virus that causes HIV/AIDS from infecting T cells that are crucial to the immune system. People whose genetic makeup includes one copy of the CCR5 mutation have delayed susceptibility to HIV infection and delayed onset of AIDS. Those who carry two copies (inherited from both parents) are resistant to HIV infection.

When presented with an HIV-positive patient who had developed chemotherapy-resistant Hodgkin lymphoma that required HCT to cure, physician scientists at University College London searched for a donor who not only provided a close genetic match for their patient but also carried two copies of the CCR5 mutation. The so-called “London patient” was transplanted in May of 2016 and has been so far cured of the Hodgkin lymphoma. He stopped taking his anti-HIV drugs in September 2017 and has remained virus-free for 18 months.  The case, reported this month in the journal Nature, marks just the second time since the outbreak of the HIV/AIDS epidemic that a patient has cleared the HIV virus as a result of HCT. In both prior cases of HIV cure, the donor cells carried two copies of the protective mutation.

Dr. Aleksandr Lazaryan

But that doesn’t mean transplants are the answer for all HIV patients, says Dr. Aleksandr Lazaryan of Moffitt Cancer Center’s Blood and Marrow Transplant and Cellular Immunotherapy Program. “With today’s medications, HIV can largely be managed and successfully controlled as a chronic condition,” he said. “HCT is not a procedure without potential serious complications, some of which might be life-threatening.” Currently, those risks are only outweighed when an HIV-positive patient presents with a cancer that requires potentially curative HCT or other non-HIV condition for which HCT is indicated. At that point, Lazaryan explained, if a suitably matched donor can be identified who also bears two copies of the HIV-resistant CCR5 mutation, “the transplant could effectively help, killing two birds with one stone.”

Lazaryan said Moffitt has considered pursuing such transplants for HIV-infected patients with concurrent blood malignancies. But finding matched donors who also carry double copies of the protective mutation presents its own challenges. “Only about 1 percent of the overall population worldwide carries two copies of this mutation. And it is more prevalent among the Northern European populations, especially those of Scandinavian descent,” which can be a limiting factor for potential transplant recipients of other ethnicities.

Lazaryan said the spread of this genetic mutation tracks the path of the Vikings, roaming Northern Europe and traveling south throughout the continent to Russia, west Asia and northern Africa. It is not found in any other human populations around the globe. “It’s thought that the origin of this protective mutation was a result of the strong evolutionary pressures from major infectious outbreaks in human history, such as the bubonic plague or smallpox. Those who carried this mutation could have had survival advantage from these major infections.” It’s hoped that further investigating this mutation and its role in clearing HIV infection in two transplant recipients will eventually lead to new treatment approaches for HIV patients worldwide.

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Ann Miller Baker Medical Science Writer 813-745-8314 More Articles

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