Proof that Aids can be cured?
The 'Berlin Patient', who was once HIV positive, has been in the clear for five years after revolutionary therapy. And the woman who discovered the virus believes his story offers hope to millions
Aids researchers believe the time may have come to think the unthinkable: a growing body of expert opinion believes a cure for HIV infection is no longer a scientific impossibility but a realistic goal that scientists could reach in the very near future.
A scientist who shared a Nobel prize for the discovery of human immunodeficiency virus (HIV) has now added her voice to those who believe it is possible to cure a viral infection that until now has been considered life-long, chronic and, although treatable, ultimately incurable.
Françoise Barré-Sinoussi, who first reported the discovery of the Aids virus in 1983 with her colleague Luc Montagnier of the Pasteur Institute in Paris, is expected later today in Washington to say that talk of a cure for HIV should no longer be a taboo subject for Aids researchers.
She will cite the case of the "Berlin Patient", an American gay man called Timothy Brown who received a bone marrow transplant in 2007 while a student in Germany. The transplant was undertaken to treat a type of blood cancer but in the process it also apparently cured Mr Brown of his HIV infection.
Five years after his transplant, he continues to be free of HIV despite having given up his anti-viral drugs. It is still not clear to scientists why Mr Brown has managed to shrug off his chronic HIV infection so effectively.
For decades, a cure for Aids has been little more than a pipe dream because of the ability of the virus to integrate itself within the genetic material of infected patients. Once installed within a patient's DNA, the Aids virus could "hide away" for years, even decades, from the body's immune defences.
As a result, scientists realised soon after HIV was discovered in the early 1980s that infected people would continue to be at risk of developing Aids throughout their life unless continuously treated with anti-viral drugs.
But Mr Brown's highly unusual case has given some scientists cause for optimism. In a comment article in this week's Nature, Professor Barré-Sinoussi and her colleague Professor Steven Deeks of the University of California, San Francisco, say that Mr Brown has been effectively cured of HIV – the first person in the world to fulfil the strict scientific definition of a cure.
"He has now been free of readily detectable virus in the absence of therapy for more than five years. In other words, he is cured. His experience suggests that HIV infection might one day be curable," they say.
Today in Washington, Professor Barré-Sinoussi and Professor Deeks will take part in the launch of a global scientific strategy document for Aids and HIV prior to the 2012 International Aids Conference which begins next week. The document will place "cure research" centre stage, suggesting that instead of focusing almost exclusively on research into better anti-viral drugs and HIV vaccines, scientists should think about ways of curing patients outright, or at least to a point where progression to Aids becomes unlikely.
"It may not be necessary to completely eradicate the virus in the individual, however. In about 1 per cent of people infected with HIV, the virus is natural controlled, such that their risks of disease progression and transmission are minimal," say Professor Barré-Sinoussi and Professor Deeks.
"Scientists have studied these 'elite controllers' in search of a path towards developing a vaccine. Elite controllers could also provide clues about how to control, if not eliminate, established infection," they say.
Elite controllers include people who carry natural mutations in a gene called CCR5. About one in 100 people have such mutations, which prevent HIV from infecting the type of white blood cells where the virus is thought to lie dormant for many years.
Mr Brown's bone marrow donor was someone who was an elite controller. As a result of the transplant, Mr Brown's white blood cells – the T cells of the immune system – were repopulated by those of his donor, apparently making Mr Brown resistant to HIV.
However, not everyone is convinced that the procedure eliminated all of the HIV from Mr Brown's body. Alain Lafeuillade, head of infectious diseases at the General Hospital in Toulon, France, has questioned whether the word cure is applicable given that some scientists claim to have found low levels of HIV "viraemia" within Mr Brown's body.
"We cannot declare 'cured' a man who still has low levels of viraemia, low levels of anti-HIV antibodies not detectable by commercially available tests," Dr Lafeuillade said.
Professor Deeks, who has followed Mr Brown's case for many years, meanwhile insists the patient has been effectively cured. "By any reasonable definition, Mr Brown is cured. He has been off drugs for over five years and has done well. If he has any virus left, which remains an unsettled question, it is clearly not of clinical relevance," Professor Deeks said.
But even if Mr Brown does continue to defy scientific dogma, the method of his cure would never be appropriate for treating the millions of people in the world who are infected with HIV. A bone marrow transplant is not only expensive and difficult to undertake, it is extremely risky – Mr Brown suffers chronic neurological problems as a result of a second bone marrow transplant he had to receive to treat a relapse of his blood cancer.
Professors Barré-Sinoussi and Deeks accept that his case is only a starting point on the long journey towards a possible cure for HIV. "The barriers to curing HIV are real, and they may prove to be insurmountable," they admit.
Profile: Timothy Brown, the 'Berlin Patient'
Timothy Brown, the "Berlin patient", was a student in the German capital in 1995 when he tested positive for HIV. He still remembers his reaction to the diagnosis.
"I was terrified. I knew people who were struggling with the disease. Some of my friends had already died from it. I don't think I'd ever felt as alone as I did at that moment," Mr Brown said.
"It didn't help matters when a friend told me that I probably only had a couple of years to live. At that time most of us viewed an HIV diagnosis as a death sentence. Cure was not a topic for discussion. I just wanted to survive."
A year later, however, it became possible to treat HIV with a combination of drugs. Mr Brown was prescribed triple combination therapy, which kept him from developing Aids.
However, in 2006 he was diagnosed with acute myeloid leukaemia. His doctor suggested a bone marrow transplant of stem cells to repopulate his white blood cells, the T-cells of the immune system. The doctor suggested a donor with a natural mutation to the CCR5 gene. This gene normally codes for a protein on the surface of T-cells that allows HIV to enter the cell. But the CCR5 mutation confers resistance to infection.
"I underwent total body irradiation to wipe out my body's immune system before receiving the transplant. I last took my HIV medications on the day of my stem cell transplant. I still have no trace of HIV in my body," Mr Brown said.
Timeline: The story of a killer virus
1981 The US Centres for Disease Control identify a new infectious disease among gay men suffering from a rare form of pneumonia and skin cancer. Later identified as the first scientific report of Acquired Immune Deficiency Syndrome (Aids).
1983 Luc Montagnier and Françoise Barré-Sinoussi, of the Pasteur Institute in Paris, identify a new retrovirus in a gay man suffering from Aids.
1984 America announces that the virologist Robert Gallo has found the cause of Aids in a virus called HTLV-3. It emerges that this is the French virus.
1985 The Hollywood actor Rock Hudson dies of Aids, the first high-profile victim.
1987 AZT, the first antiviral drug to treat HIV, becomes available. UN launches global programme.
1990 Actor Ian Charleson dies of Aids, the first showbusiness case in the UK.
1991 Queen vocalist Freddie Mercury dies of Aids aged 45.
1992 The first experimental combination therapies are introduced, where patients are given two or more anti-retroviral drugs.
1995 New type of anti-retroviral known as a protease inhibitor is launched. Highly active anti-retroviral therapy now possible. Death rates plummet.
1998 HIV infection rates estimated to have doubled over three years in 27 countries.
2000 The South African Judge Edwin Cameron, the first high-profile official in South Africa to confirm he is HIV positive, condemns President Thabo Mbeki for denying the link between HIV and Aids.
2002 HIV/Aids is leading cause of death for people aged between 15 and 59.
2005 US health officials recommend use of antiviral drugs for post-exposure prophylaxis against HIV.
2007 Timothy Brown receives bone marrow transplant and is later declared "cured" of HIV.
2008 Barré-Sinoussi shares Nobel prize for HIV work.
2012 Barré-Sinoussi calls for "cure research" to eliminate HIV.