The aim of Dr Lucy Dorrell's research is to develop immunotherapy to reduce the dependence of those infected with HIV-1 on their current treatment - antiretroviral therapy (ART). This is because 9 million of the estimated 33 million people living with HIV/AIDS today are not able to access the ARTs which they are in immediate need of.
There are currently around 91,000 people in the UK living with HIV/AIDS. HIV is a challenging target because it can mutate its genetic makeup. We are trying to deal with this by developing a vaccine which focuses the immune response on parts of HIV that it cannot change easily without weakening itself.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside
Q: What happens when people are infected with HIV?
LD: When HIV gets into the body it infects and destroys the immune system. It does this by infecting a specialised kind of cell called a CD4 T cell. CD4 T cells play a really critical role in controlling and regulating how the body copes with responses to a whole range of microbes. So when these cells are destroyed and depleted over time they can fall to a critical level. At that point the individual can become seriously ill just from exposure to relatively harmless germs in the environment and that is what indicates that they have AIDS.
Q: Can you explain why it can take years for AIDS to develop?
LD: The body has a very large reserve of CD4 T cells and although a large proportion of them are destroyed in the earlier stages of the infection, the body can cope for a while and it takes quite a number of years before they fall to dangerous levels. There is a minority of infected individuals who seem to be able to live for ten or twenty years without showing any signs of illness and by studying these rare individuals we have some clues as to why it takes a long time to develop AIDS. Clearly the genetic makeup of the individual plays a part and in particular the genes that code for specific components of the immune response seem to be important in determining how long it takes to develop AIDS.
Q: What are the most important lines of research that have developed over the past five or ten years?
LD: Over the past ten years researchers have started to piece together the process of the immune response to the virus from the very earliest stages of infection. What has become clear is that HIV is extremely versatile. It seems to be able to cope with and outwit just about any immune defence that the body throws at it which makes it an extremely difficult target for a vaccine. On the positive side there have been huge improvements in treatment. HIV is treated with combinations of drugs called antiretrovirals and these drugs have improved enormously in recent years. Nowadays if you are a person with HIV living in the UK where treatment is freely available you can expect to have a pretty much normal life span if you are diagnosed early.
Q: How big a problem is HIV in the UK today?
LD: It is estimated that there are about 88,000 people living with HIV and worryingly about a quarter of those are not aware of their status so they can unknowingly pass the infection on to other people. In recent years the largest increases in cases of HIV have been among heterosexuals.
Q: How does your research fit into Translation Medicine within the department?
LD: The goal of our research is to develop a vaccine to prevent HIV infection, but also to use vaccines in combination with drug treatments to try and help infected individuals get rid of the virus from their body. HIV is an extremely challenging target because it can mutate its genetic makeup. The way we are trying to deal with this has been to develop a vaccine which focuses the immune response on parts of HIV that it cannot change easily without weakening itself. We now have vaccines in clinical trials in Oxford both in healthy volunteers and in patients, testing out this strategy and we have some early encouraging results.