Thirty-five years after it first hit the headlines, HIV (Human Immunodeficiency Virus) is still a major threat to health worldwide with an estimated two million new infections each year and one million deaths each year from AIDS (Acquired Immune Deficiency Syndrome) caused by HIV.

HIV is a virus that damages the cells in the human immune system and weakens our ability to fight everyday infections. It is now effectively controlled with antiretroviral drugs, so that people in wealthy countries who adhere to the treatment and have reliable access to the medication will normally have a life expectancy that is close to the average - but only with lifelong treatment.

In poorer countries without universal health services, patients are at a life-threatening disadvantage as treatments are not always freely available and supplies can be unreliable. Critically, if treatment is interrupted for any reason, the virus is reactivated and that can be a death sentence.

Over the last year, the Evelyn Trust has been funding research led by Professor Andrew Lever with Dr Mark Wills and Dr Hoi Ping Mok at the Department of Medicine, University of Cambridge, to investigate viral latency and reactivation. This is the mechanism by which viruses such as HIV ‘sleep’ and then ‘reawaken’ when treatment stops. 

Professor Lever explains that he has been looking for answers to several key questions. 

“We need to resolve some central issues before we can make progress on viral latency. What is the mechanism which causes these viruses to ‘sleep’? Which cells are harbouring these ‘sleeping’ viruses? Can we ‘wake’ them up and destroy them by boosting the immune response? If we can, then we are on the way to the ultimate goal of our work which is a cure for HIV. 

We’ve had success in the last year in using deep sequencing techniques to look more closely at latent viruses. We know that a ‘sleeping’ virus is still producing detectable virus at a low level. We’ve also demonstrated that a majority of the latent viruses that can be reactivated are genetically distinct, but they don’t seem to be evolving very much so these are reservoirs that are stable and not repeated new infections of new cells. This is important, as it helps guide the best approach to eradicating the infection. But we are still seeking to understand what exactly causes a virus to sleep in the first place and why some cells seem to be easy to ‘wake up’, while others don’t.” 

Providing answers to these complex questions will take time, but Professor Lever’s research is making significant headway.

“An additional key objective for our work when we applied for funding from the Evelyn Trust was the simplification of the blood sample testing - or ‘assay’ - for latent viral load. This complex assay has been a major handicap in our ability to properly measure the results of attempts to eradicate HIV. We’ve successfully improved it, making it much quicker, more efficient and ultimately less expensive which will have immediate benefits for researchers, health systems and patients. Our new assay has just been used in over 100 blood samples in a collaborative clinical trial between Cambridge, Oxford, UCL, Kings and Imperial College. We await the results of the trial to see if we have made progress in eliminating HIV completely.” 

For more details of the work of Professor Lever’s group, visit www.med.cam.ac.uk/lever1/