by Professor Sharon Lewin
The announcement made last week that two HIV-infected men in Boston were able to stop their anti-HIV drugs without evidence of the virus returning has not surprisingly made headlines across the world. Coming so soon after the equally heavily publicised cases this year of the “functionally” cured `Mississippi baby´ and the 14 adults living with HIV in France who are all doing well some nine years after being taken off antiretrovirals, it is understandably generating a public perception that perhaps we are in fact inching closer to a cure for HIV. However for those of us working in the field, all these cases raise as many questions as they answer.
So where does that leave us? Where exactly are we in terms of finding a cure for HIV? And why is the search for a cure back on the agenda at a time when current treatments for HIV, called antiretrovirals, taken at the right time are able to provide people living with HIV a normal life expectancy?
Antiretrovirals have delivered one of the most spectacular scientific advances in recent decades. They can block the virus from infecting new cells and very effectively keep the virus under control for many years. These highly effective drugs significantly prolong life and at the same time dramatically reduce a person’s infectiousness. They have literally saved millions of lives, families and communities.
But the drugs have their limits; if the antiretrovirals are stopped, the virus resurfaces in blood – on average within three to four weeks. This happens because the virus can hide in certain blood cells and can essentially “go to sleep” and become invisible to the drugs and the patient’s immune system. These long lived “reservoirs” of virus persist indefinitely. Therefore, patients require life long treatment – which comes with substantial costs and some long term side effects.
There are currently 33 million people living with HIV – all of whom at some stage will require antiretrovirals. In 2012, close to 10 million people in low and middle income countries were receiving antiretrovirals – another great success story. But the costs of maintaining this as well as increasing access to the many more that need treatment are now substantial. Health systems and funding bodies are already struggling to foot the bill.
Finding a cure for HIV – or a way for patients to safely stop antiretrovirals and keep their virus under control – will therefore have a very significant global economic and personal impact.
The big challenge is this: how to find a way to permanently knock out these last “reservoirs” of the virus.
So what do the Boston patients bring to the table in the jigsaw of HIV cure research?
For one, we know that after a stem cell transplant, the foreign blood cells slowly eliminate the patient’s own blood cells. This is how the stem cell transplant controlled the lymphoma in the Boston patients. These new foreign blood cells were “protected” from infection because the patients were taking antiretrovirals. The patients’ doctors then asked an important question – did the foreign blood cells also eliminate the HIV reservoir? The answer appeared to be a resounding “yes”: as early as 6 months post-transplant.
But because the virus can hide only to re-emerge once antiretrovirals are ceased, the critical question was what would happen if and when those drugs were in fact ceased. What we know so far is that eight and 15 weeks after stopping the antiretrovirals, neither patient has evidence of virus detected in their blood.
Does this mean they are truly cured? This is harder to answer and as the researchers acknowledged in Kuala Lumpur, we’ll be able to draw much more solid conclusions after 12 months, perhaps even two years. It is probably more accurate to say that the two patients are in “remission”, a cautious word but a more realistic one because we just don’t know at this stage of the game if and when the virus will return.
One lesson the Boston patients definitely do not teach is that anyone with HIV infection should now be lining up for a stem cell transplant. Transplantation is a high risk procedure with over 20 per cent mortality. The Boston patients had the transplants because they had lymphoma – not because they had HIV.
But these cases will open up new avenues of research. Can we modify the transplant procedure to eliminate the HIV reservoir but not totally wipe out the patient’s own cells? Could the same result be achieved with some but not all of the complex treatment? Can this outcome be mimicked with a vaccine that activates the patient’s own immune response against the reservoir?
Globally and in Australia multiple other ideas are already being tested to tackle the formidable HIV reservoir – waking the virus up or ensuring the virus sleeps forever or even using gene therapy to effectively make a patient’s cells permanently resistant to HIV. It’s early days, but the scientific advances since the International AIDS Society launched the Towards an HIV Cure initiative three years ago have been impressive.
The Boston patients have taught us that HIV can indeed go into remission – and maybe one day cured. The challenge now will be the “why” and “how” and ultimately to use this knowledge to find new drugs to develop a cure for all people living with HIV – rich or poor. These are just the first steps down a long road ahead but they are nevertheless the vital ones we need to take.