An international team of scientists is reporting the "functional cure" of an HIV patient for only the second time ever. Known only as "the London patient," the man received a transplant of bone marrow stem cells from a donor that had a resistance to the virus. The patient has now been in remission for 18 months, with no sign of the HIV-1 virus in his bloodstream. But as exciting as the news is, there are a few caveats.
The research was conducted by scientists at the University of Melbourne, the Westmead Institute for Medical Research, and the University of Cambridge. The London patient was diagnosed with HIV in 2003, and then advanced Hodgkin's lymphoma in 2012. To treat that cancer, he received bone marrow stem cells from a donor who had two copies of a particular mutation to the gene CCR5, which makes them more HIV-resistant.
Antiretroviral therapy (ART) is a common method of managing HIV infection, but 16 months after the transplant, the patient was successfully taken off that treatment. It's now been a further 18 months since stopping ART, and levels of HIV-1 RNA and DNA are still so low as to be undetectable. That means the London patient is in remission and appears to be effectively cured, although the research team is reluctant to jump to that conclusion too early.
This is only the second recorded time a patient has gone into HIV remission. The first case occurred in 2007, when "the Berlin patient," later identified as American man Timothy Brown, underwent a similar, albeit more aggressive, treatment.
Brown also received bone marrow stem cells from a donor with the same kind of genetic mutation, this time to help treat leukaemia. But he was also treated with total body irradiation as well, a risky procedure that can help the bone marrow transplant take hold. On top of that, Brown suffered from multiple complications that had the potential to turn deadly.
Because of all those factors, scientists had been unable to replicate the success of the treatment in the years since. But now, the new study confirms that the first time wasn't a fluke, and better yet, it can be done less aggressively than it was with Brown.
Interestingly, one of the complications that both the Berlin and London patients experienced might play a key role in the treatment. Both men went through graft-versus-host disease, which is basically the reverse of rejection – instead of the patient's immune system attacking the transplant, cells in the transplant attack the host's body. It's believed that the transplanted stem cells might help to eliminate host cells that are still infected with HIV, preventing the virus from returning.
As promising as it is to have confirmation that a functional HIV cure is possible, overall it might be too complicated and risky for regular use.
"The cost benefit of the prognosis following a bone marrow transplant versus that on HIV antiretroviral therapy needs serious consideration," says Professor Anthony Kelleher, Director of the Kirby Institute at UNSW Sydney. "Secondly, naturally resistant and compatible bone marrow donors are rare because of the need for donor recipient matching. Further, this type of procedure is not widely available in many countries. Finally, there is significant morbidity and mortality associated with this type of transplantation, even when conducted in the best centers, and under the best circumstances."
But there's still hope. Having shown that blocking the CCR5 gene works to fight HIV, the researchers suggest that gene therapy could be a less invasive treatment in future. And sure enough, CCR5 is the very gene targeted by Chinese scientists in the recent and highly controversial birth of the world's first gene-edited babies.
The research was published in the journal Nature.
Source: University of Cambridge, Springer Nature
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