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Timothy Ray Brown, the first person to have been cured of HIV, left a lasting legacy in the HIV community when he passed away from acute myeloid leukemia on 29 September 2020. As the “Berlin patient”, he inspired millions of people living with HIV and scientists working towards a cure. This World AIDS Day, Dr Jori Symons reflects on Timothy’s generous contribution to science and tireless advocacy that has influenced the course of HIV history.

By University of Melbourne Dr Jori Symons, postdoctoral research fellow at the Doherty Institute

The first time I met Timothy was - funnily enough - at the Cure Bar in Washington DC.

It was 2012 and I had been studying his case for quite some time. It had been five years since Tim had stopped taking his antiretroviral medication after undergoing an experimental stem cell transplant for leukemia, with cells sourced from a donor who had a genetic mutation of the CCR5 gene (D32 mutation). This gene is necessary for HIV to enter the cells, however the mutation ensures that CCR5 is not present on the cell surface, making his brand new immune system resistant to HIV. I’d been in Washington DC presenting the science behind Tim’s case at a conference, and he was fascinated to learn more about it. I was struck by how softly spoken Tim was, and that he was always smiling. He was beaming that night, in fact, because he was very proud to be the first person cured of HIV - he actually told everybody at the Cure Bar. That was the first time that I met Tim and there would be many more encounters over the years.

Tim was a brave man, facing incredible odds over his lifetime. There was a one in 25 million chance of finding the right stem cell donor for his leukemia with a complete Human Leukocyte Antigen (HLA) match and homozygous for Delta 32. This reduced the chance that the donor immune cells would recognize Tim’s body as foreign, and the D32 mutation was in both genes of the donor cells. When Tim prepared to undergo the stem cell transplant in 2007, there was a 50 per cent chance that the procedure would kill him. He received the transplant on 6 February, 2007 and referred to it has his new “birth date”. Three months after the transplant, HIV was no longer found in Tim’s blood. That moment secured his place in medical history.

Tim was generous with his body, his time and his life. He was poked and prodded an awful lot, donating samples broadly, including a gut biopsy and even a brain biopsy - although this was taken for suspected leukemia. No HIV was found in any of the biopsies. He said that he did this because he was the first person globally to be cured of HIV and he did not want to be the last. It was this hope that drove Tim’s efforts, and he was a determined advocate for HIV cure research.

When Tim released his name to the media in 2010, he went from being the “Berlin patient” to Timothy Ray Brown – the first person to have been cured of HIV. I believe that this marked another turning point HIV in cure research, because scientists could actually see him and see that it was possible. There is now a group of people living with HIV who have also had stem cell transplants, and some were transplanted with cells with the same D32 mutation. There have also been others who seem to have been cured of HIV, namely Adam Castillejo (the “London patient”) and the “Dusseldorf patient”.  The procedure they underwent was inspired by Tim.

Stem cell transplantation with D32 donor cells has - so far - been the only procedure that has cured people of the HIV infection. It is a highly risky procedure with high mortality rates, so it is only used to treat underlying blood malignancies - curing the HIV infection is really a designed side effect. This approach is unfortunately not a strategy that can be widely applied to cure all people with HIV.

Currently, most HIV cure strategies focus on eliminating sleeping (latent) virus by “shocking it awake” with latency reversal drugs. This should allow the immune system to kill the infected cells. This “shock and kill” strategy is a hot topic in cure research but further research is required to create a good shock and to strengthen the immune response to effectively kill the infected cells.

As the HIV community gathers virtually this year for World AIDS Day, it’s an opportunity to celebrate Tim’s life, his legacy, and the continued impact of HIV on millions of people globally. Over the course of Tim’s life, medical advances have changed the way that we treat HIV, allowing HIV positive people to live with the virus for many years. It is important to recognise, however, that they will continue to live with the impacts of the virus until we – ultimately – find a cure for HIV. For scientists and people living with HIV globally, Tim is still a sign of hope that this might be possible.

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