A cure for HIV?
Timothy Ray Brown has recently been heralded as the ‘first man to be cured from HIV’, we look at what this means in terms of finding a universal cure for the 34 million people currently living with HIV (WHO
, 2010). He has now been HIV-free for five years and also recovered from leukaemia all thanks to a bone marrow transplant from an ‘elite controller’.
HIV is a virus that is spread from one infected person to another by the transfer of bodily fluids. The virus infects and replicates by binding and entering white blood cells frequently resulting in the death of the cells.Over time this results in the gradual failure of the immune system and the onset of AIDs in the infected individual. Currently the best therapy for people diagnosed with HIV is combination anti-retroviral therapy. These are drugs that aim to induce remission of HIV disease, leading to a near normal life-expectancy, decreased mortality and an improved quality of life for patients. The drugs work by interfering with the life cycle of the virus preventing it from replicating and damaging the immune system. This treatment however isn’t a cure and when most patients stop taking anti-retrovirals the virus becomes active again so patients have to take the drugs every day for their entire lives.
Diagnosed with HIV whilst living in Berlin in 1995, Timothy Brown accepted the idea of taking combination anti-retroviral therapy for the rest of his life. However 11 years later in 2006 he was diagnosed with acute myeloid leukaemia (AML), after two rounds of chemotherapy his leukaemia hadn’t entered remission and so he required a bone marrow transplant also known as a peripheral blood stem cell transplant. When it transpired that he had an almost unheard of 262 possible stem cell donors his doctor, Gero Hütter started looking for possible HLA-matched donors who were also ‘elite controllers’.
An ‘elite controller’ is someone who has high (but often not complete) resistance to HIV-1 infection. This is because of a mutation in the gene for the CCR5 receptor which renders it useless. The CCR5 is a receptor on the surface of white blood cells that is needed, alongside the CD4 receptor, in order for HIV-1 to enter and infect cells. The deletion mutation associated with 'elite controllers' occurs in about 1% of the white population and has been linked to the Black Death in Europe in the 14th Century. When the Black Death initially struck, very few people had the CCR5 mutation, however by the time of the culmination of the outbreaks with the Great Plague of London in the 1660s many people carried the mutation as it was protective against the plague.
Amongst the possible donors for Timothy Brown there was one who also had the mutation and so was an ‘elite controller’. After undergoing a regimen to completely removing his own cancerous immune system Timothy Brown received the transplant. The day prior to his transplant in 2007 was the last day he took his antiretroviral therapy. Three months on, multiple biopsies revealed that there was no more HIV-1 DNA in his body. Unfortunately 9 months later his AML relapsed again and had to receive another stem cell transplant from the same donor, however his HIV hadn’t and five years later he ‘feels great’.
The question that now stands is whether this miracle can be replicated for the 34 million other people who are still living with HIV, and whether the outcome can be replicated using lower risk procedures. It would be impossible to give stem cell transplants both financially and logistically to all infected however Dr Ravindra Gupta, a research fellow at University College London felt that his was an exciting step and that optimistically this could mean that within five to 10 years we could have a scalable intervention for HIV in the form “either a cure strategy or a vaccine”. Currently only 8 million of the 14 million identified as needing anti-retroviral therapy are receiving it and so the focus still needs to be on increasing accessibility to medications which have decreased HIV mortality by around 20%. Dr Gupta said that he felt the emphasis needed to be on keeping the momentum going in order that treatment can be given to those who need it, and that resistance to therapies can be kept low as well as making sure that science keeps moving at a sustainable pace.
So, whilst this may not provide the miracle cure for all infected Timothy Brown’s story certainly provides yet another small step in the journey to finding a strategy for tackling HIV.
This article is based on an interview with Timothy Brown and Dr Gupta on the BBC Radio 4 Today Programme which can be accessed here
Read more about the Timothy Brown’s story and donate to his foundation by going to his website
Long-Term Control of HIV by CCR5
Delta32/Delta32 Stem-Cell Transplantation (2009) Hütter et al. NEJM
Did Black Death boost HIV immunity in Europe? (2005) Hopkin. Nature