MICA: ERADICATE HIV-1: TARGETING THE HIV-1 RESERVOIR WITH NEW IMMUNOTHERAPEUTIC STRATEGIES

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There is no cure or vaccine for HIV infection. My aim is to explore new strategies for finding a cure for HIV infection. Thirty four million people are estimated to be infected with HIV - nearly 1% of the global adult population. Of these, 8 million are in receipt of antiretroviral therapy (also called 'ART'), but provision of ART to all who need it is a major logistical and financial challenge. Not only do patients have to stay on therapy for the rest of their lives, but there is the risk of drug resistance, side effects and stigma. We are also starting to learn that patients on ART develop other illnesses - such as heart disease, cancers and early dementia - that we do not fully understand. There is a growing understanding that although current HIV therapies have saved millions of lives, sustaining this for the future may demand new strategies. The most challenging of these is to find a cure for HIV.HIV spreads widely in the human body in the first days after infection. Upon the use of potent ART the amount of residual virus declines dramatically. However, despite many years of continuous treatment the population of infected cells does not disappear completely - there is a 'reservoir' of infected cells. This tiny but dangerous reservoir of cells has the capacity to grow out and restore the original disease state. If all infected cells could be eradicated this would constitute a cure, but this has only been achieved in one individual and involved the radical step of bone marrow transplantation as well as potent chemotherapy - not a solution applicable to the millions of infected people. The research will tackle key questions that need to be answered to achieve a cure for HIV. Can we wake up this 'reservoir' of infected cells so that the immune system can attack them? What is the best way to measure the 'reservoir' to assess if a patient might be cured? Are there patients who are more amenable to cure than others - in particular does treatment given very early after infection result in a period of 'remission' in which the patients can stop the drugs without the virus coming back?The answer to any of these will impact the field significantly. The research will be carried out by Dr John Frater and his team at the University of Oxford, collaborating with researchers across the UK and internationally. The research will be a mixture of laboratory experiments to see how infected cells behave under different conditions and clinical studies in which samples from patients will be tested to try and understand how best to target the reservoir of persisting infected cells.The studies will be conducted in three related workstreams. In the first, the researchers will study whether cells that contain silenced or 'latent' HIV can be 'woken up' using drugs normally used for cancer and whether the immune system will be able to recognise them. In the second workstream, a new test will be developed for measuring the reservoir using a combination of two techniques - one to measure the amount of viral DNA in the infected cells, and the other to use new genetic technologies to infer whether the viral genes can produce viable replicating viruses. Our aim is to develop and apply the technique, with the potential to bring it into clinical practice. Finally, in the third workstream, the researchers will develop new cohorts of patients treated very early in infection. Early treatment may be a key part of any cure, as the reservoir of infected cells at this stage looks more susceptible to new therapies. By developing these cohorts of adults and children, I aim to provide a platform to do this and conduct tests to see whether a cure might be feasible.In summary, the research comprises an exciting series of objectives. The need for an HIV cure is great, and if proof-of-principle can be gained in any of these key directions, it would be a major step forward.