A cure for Aids is a step closer, scientists believe, after a bone marrow transplant that has left a London patient HIV-free for 18 months.
The success in London, 12 years after Timothy Brown, the so-called Berlin patient, underwent a similar transplant, was hailed as a key moment in the long hunt for a cure.
“Although it is not a viable large-scale strategy for a cure, it does represent a critical moment in the search for an HIV cure,” said Anton Pozniak, the president of the International Aids Society. “These new findings reaffirm our belief that there exists a proof of concept that HIV is curable. The hope is that this will eventually lead to a safe, cost-effective and easy strategy to achieve these results using gene technology or antibody techniques.”
Has the London patient been cured of HIV?
The unidentified patient has been free of HIV for 18 months after stopping the antiretroviral drugs that keep people healthy. Technically he is in remission. His doctors say he could be considered cured after maybe three years in the clear. Timothy Brown, once known as the Berlin patient after the city where he was treated, has been HIV-free for 12 years and is said to be cured.
Can anyone have this treatment?
Ridding both men of HIV was a side-issue, in spite of the huge implications for research. Each one had cancer, was very sick and needed a bone-marrow stem-cell transplant to save his life. This is not something that would be carried out other than in such last resort situations because it is risky and HIV is no longer necessarily fatal. People remain healthy with normal life expectancy on daily pills.
How did they eliminate HIV?
The scientists searched for a stem cell donor carrying a genetic mutation that prevents expression of an HIV receptor called CCR5. Such people are rare, making up only 1% of donors. They are immune to the virus. It is not known whether the mild graft-versus-host disease – where the donated cells attack the body’s cells – that both men experienced may also have played a role in the loss of HIV-infected cells.
How does this move things on?
A second probable cure shows that the first was not a fluke. It will also encourage scientists to pursue the possibility of using gene-editing to alter CCR5 so that it will no longer act as a gateway for HIV to enter cells.
Sarah Boseley, Health editor
Brown, known as the Berlin patient until he revealed his identity, made history. Like the London patient, he had a stem-cell transplant as a last resort to treat a life-threatening cancer. Doctors decided to attempt to clear HIV at the same time, seeking a stem cell donor with a rare genetic mutation of the CCR5 gene for both Brown and the London patient to make them HIV-resistant.
Brown came off the antiretroviral drugs that suppress HIV and has been virus-free ever since. The London patient, who does not want to disclose his identity, stopped taking the medication 18 months ago and there is no sign of a return of HIV.
The procedure in itself can never be offered as a cure for HIV infection because stem cell transplants carry unacceptable risks. People with HIV can stay fit and well with a normal lifespan by taking a daily pill.
Prof Ravindra Gupta from University College London, the lead author of the paper on the successful treatment of the London patient, published in the journal Nature, said the way forward could be editing of the CCR5 gene, which allows HIV to enter cells.
“A field was generated as a result of the Berlin patient looking at CCR5 gene editing,” he said. “You may have heard of the Chinese babies that were having experimental knock-out of that particular gene.”
The Chinese scientist who edited the genes of babies in the womb to make them resistant to HIV was condemned around the world because the experiment was unnecessary and carried risks. But, said Gupta, CCR5 gene editing in infected patients was a justifiable goal. “What this second case says is this is a bonafide research target and probably the most promising we have for any HIV cure,” he said.
However, CCR5 resistance may not have been the only reason for the disappearance of HIV. The Berlin and London patients both experienced graft-versus-host disease, in which donor-immune cells attack the recipient’s immune cells. That may have played a role in the loss of HIV-infected cells, Gupta said.
Seeking a cure is important, said Gupta, who treated the patient while at UCL but is now at Cambridge University. Although millions of people are now stable and healthy on antiretroviral drugs, he said, that was not the long-term solution to the Aids epidemic. “There are 36 million-odd people with HIV worldwide. The aim is to get everybody on treatment for the rest of their lives and that’s a huge undertaking both for drug delivery but also making sure people can stay on medication for decades. There is a cost issue for developing countries.”
Brown, from the US, was treated in Germany in 2007. He was suffering from acute myeloid leukaemia. The London patient was diagnosed with Hodgkin’s lymphoma in 2012 and, unlike Brown, did not have radiotherapy although both had chemotherapy. He remained on antiretroviral drugs for 16 months after the transplant, before he and his doctors decided to stop them.
Regular blood testing has showed no sign of the virus during the past 18 months. After about three years, said Gupta, scientists would feel fairly confident the virus would not come back.
His patient, he said, was very happy. “It’s been a long journey. He’s been very sick for a long time. Obviously the idea of cure and remission has created a certain level of anxiety and hope mixed in with each other.
“We’ve been talking about this for a few years now. It’s been a difficult journey to offer someone this hope and then say we don’t know it’s going to work. So even stopping his HIV treatment: he had to really think about it and it took him a while to finally do it. It’s difficult because you’ve got to put your faith in what doctors are saying to you.”
Sharon Lewin, the co-chair of the Towards an HIV Cure initiative of the International Aids Society, said the successful treatment of a second patient was important. “To me, that’s a big deal,” she said at the annual Conference on Retroviruses and Opportunistic Infections in Seattle, where the work was also presented. “If you have a single case in medicine, you never know if it was an unusual coexistence of conditions you don’t fully understand.”
The Berlin and London patients had the transplants as a last resort, because they were very seriously ill from cancer. “Transplantation in and of its own would never be an intervention for cure,” she said. But this success had generated new avenues for research, including CCR5 gene editing.
