Miranda Smith
From Berlin to London: making sense of HIV cure claims
For over 12 years, Timothy Ray Brown, known as the ‘Berlin Patient’, has been the only person to be cured of HIV infection. At the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, researchers have detailed a new case, known as the ‘London Patient’ who may be the second. The case has also been published in Nature.
This case is exciting because it seems to show that Timothy Ray Brown’s case was not a fluke. But the London Patient is still highly unusual. Even if HIV never returns in the London Patient, it is not a strategy that could be used in the millions of others living with HIV around the world. This case has the potential to teach us more about how HIV persists and where new research should focus.
What happened to the London Patient?
The London Patient had been living with HIV for about ten years when he was diagnosed with a type of blood cancer.
After some difficulties treating his cancer with chemotherapy, doctors performed a stem cell transplant. His transplant came from a closely matched donor who lacked the CCR5 co-receptor for HIV. The London Patient stayed on antiretroviral treatment throughout the transplant process. The transplant was successful, and he stopped his antiretroviral treatment about 16 months afterwards.
At all times since the transplant, his HIV viral load has been undetectable, including during the 18 months off treatment. Since the transplant, no traces of infectious HIV have been found.
How does it compare to the Berlin Patient?
There are a lot of similarities between the two cases, but they are not identical.
Both people had long-term, controlled HIV infection and then contracted blood cancers. The Berlin Patient had Acute Myelogenous Leukaemia, and the London Patient had Hodgkin Lymphoma.
The Berlin Patient had a very harsh conditioning regime to prepare for his transplant. Conditioning prepares the body for transplant – it makes space in the bone marrow and reduces the immune response that might affect it. The conditioning regime was much gentler for the London Patient.
The Berlin Patient received a total of two transplants from the same donor, as he experienced a cancer relapse after the first. The London Patient has only received a single transplant.
Both people experienced mild graft-versus-host disease after transplant. This is a common consequence of bone marrow transplant. If the transplanted cells are not a perfect match to the recipient, they can see the rest of the body as foreign and attack them. Both the Berlin and London Patients experienced mild forms of graft-versus-host disease.
The Berlin Patient stopped treatment for HIV just before his first transplant. It is now over 12 years since then and his HIV has remained undetectable for that whole time. On the other hand, the London Patient continued treatment throughout the transplant process and for over a year afterwards. The London Patient stopped treatment about 18 months ago, and his HIV has remained undetectable since that time.
What does this all mean?
The London Patient is exciting because it shows that the Berlin Patient was not a one-off. It is yet to be seen if the London Patient will continue to have undetectable virus. It is too early to say that this is a cure, but it is definitely a case of long-term remission.
Professor Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, reflects on how we should refer to the London Patient:
Do we say he’s cured, or do we say he’s in remission? Probably remission’s a better word because it’s possible the virus could suddenly come back at some time, and we just haven’t had enough experience with people who can control their virus for such a long time to know if it will pop up within the next few months. I’d say if he stayed with an undetectable viral load for 2 or 3 years we would have greater confidence in calling him cured as we do with Timothy Brown.
Professor Sharon Lewin
The critical question is what does this mean for people living with HIV? In the short term, the answer is not much. Keep taking your prescribed antiretrovirals. Stem cell transplants are risky. They will never be done in people who are otherwise healthy.
In the longer term, the London Patient can help focus research around two issues.
The first is around the role of the CCR5 co-receptor. Both the Berlin and London Patients had remarkable responses to the removal of CCR5 from blood cells. Can a form of gene editing do this in people living with HIV without needing a bone marrow transplant?
The other issue is the potential for immune responses to clear the HIV reservoir. The London Patient experienced mild gut-related graft-versus-host disease which may have helped clear remaining HIV-infected cells.
The London Patient is a significant development, but should be kept in perspective.
See Brent Allan discuss the study with Sharon Lewin here:
See Brent Allan talk to James McMahon about the study here:
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