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British scientists to trial potential HIV cure: HDAC Inhibitor + HIV Vaccine
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by Sam Wong 26 November 2013
http://www3.imperial.ac.uk
Dr Sarah Fidler with student Andrew Broadbent.
Scientists and clinicians from five leading UK universities will begin a groundbreaking trial next year to test a possible cure for HIV infection.
Efforts to cure HIV in the past have been thwarted by the virus's ability to lie dormant inside blood cells without being detected. The new therapy combines standard antiretroviral drugs with two new weapons: a drug that reactivates dormant HIV, and a vaccine that induces the immune system to destroy the infected cells.
Fifty patients in the early stages of HIV infection will take part in the trial. The researchers hope that within months, the stores of hidden HIV in these patients - called the HIV reservoir - will be significantly reduced. They expect to know the results in 2017.
The trial is being conducted by the CHERUB collaboration - an alliance of HIV researchers at Oxford University, Imperial College London, the University of Cambridge, University College London and King's College London. It is being funded by a 1.7 million grant from the Medical Research Council (MRC), as part of the Biomedical Catalyst funding stream.
"Our research in the labs has led to some very promising results. We now have the opportunity to translate that into a possible new treatment."
- Dr Sarah Fidler
Department of Medicine
Key preliminary studies by the CHERUB researchers that laid the groundwork for the trial were supported by National Institute for Health Research Biomedical Research Centres (NIHR BRCs) based at the five universities and their NHS trust partners.
Thirty-four million people are infected by HIV worldwide. Antiretroviral therapy (ART) is highly effective at stopping the virus from reproducing, but it doesn't eradicate the disease, so it has to be taken for life.
HIV carries its genetic code in RNA, a molecule related to DNA, but as part of its lifecycle it copies the code into DNA and merges it with the DNA of human cells it has infected. In some cells this DNA remains dormant (latent) enabling it to stay hidden from the immune system and resist therapy.
Drugs called HDAC inhibitors, which are used as cancer treatments, have been shown to reactivate dormant HIV in the laboratory.
One group of patients in the trial will be given a short course of HDAC inhibitors and an HIV vaccine alongside ART. Another group will get ART with placebos. As part of the study the research team are developing an improved method for detecting latency, which has been one of the difficulties in measuring the success of therapeutic approaches such as this.
The researchers, led by Dr Sarah Fidler at Imperial and Dr John Frater at Oxford, hope the trial will provide proof that a cure is feasible.
"We can only truly know if someone is cured of HIV if we stop giving them antiretroviral therapy," said Dr Frater of Oxford University. "We're not going to do that, but we will test if we can reduce the number of HIV-infected cells in these patients. If we can, it will prove in principle that this strategy could work as a cure, even though it will need many more years of further development."
"We know that targeting the HIV reservoir is extremely difficult," said Dr Fidler, "but our research in the labs has led to some very promising results. We now have the opportunity to translate that into a possible new treatment, which we hope will be of real benefit to patients."
Professor Dame Sally C. Davies, Chief Medical Officer and Chief Scientific Adviser at the Department of Health, said: "Research has changed HIV into a long term condition. I am pleased that the world-leading collaborative research within the National Institute for Health Research Biomedical Research Centres has provided the foundations for this major new trial."
The trial will begin recruiting patients next year. For more information go to www.cherub.uk.net
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New HIV Cure Study in UK, The RIVER Study: HDAC inhibitor+ HIV Vaccine
www.thetimes.co.uk
"A potential cure for HIV will be tested on British patients next year in a ground-breaking trial of a treatment that aims to put sufferers into cancer-style remission.
The virus will be "woken up" from its hiding place within cells so that it can be targeted by a combination of drugs, in a first-stage study by a group of five leading universities supported by the Medical Research Council.
Although the 50 patients involved are unlikely to be cured, scientists hope that their reservoir of hidden HIV will be cut significantly, showing that the method has the potential to cure the condition in further studies. Even if the trial succeeds, it will be many years before any treatment is ready for routine use.
About 100,000 people in Britain have HIV and many live normal lives using antiretroviral drugs, which stop the virus from spreading within the body. A reservoir of the virus lies dormant within blood cells, however, and would re-emerge if patients stopped taking the drugs, potentially leading to Aids.
The UK trial will use a new chemotherapy drug to stimulate the virus so that it becomes visible to the immune system. The drug will be combined with a vaccine designed to kick-start the body into attacking HIV-infected cells.
"It feels counter-intuitive - why would you want to wake the sleeping virus in patients?" said John Frater of the University of Oxford, one of the trial leaders. "By using this drug, we can wake up HIV and that means the cells become targets. Previously they were camouflaged."
Half the patients will receive HDAC (histone deacetylase) inhibitors, alongside the vaccine, while the rest will get a placebo. Both groups will also take standard antiretrovirals.
"We will test if we can reduce the number of HIV-infected cells in these patients. If we can, it will prove in principle that this strategy could work as a cure, even though it will need many more years of further development," Dr Frater said.
Sarah Fidler, of Imperial College London, another project leader, said: "Research in the labs has led to some very promising results. We now have the opportunity to translate that into a possible new treatment."
She added that the ultimate aim was "to look at HIV a bit like the cancer model, where you are in remission and can come off your drugs".
Clinics in London and Brighton will ask for volunteers who have recently become infected, as treating the virus in the early stages offers the best chance of beating it. This means most recruits will be gay men who test regularly and know when they were infected.
"For many people this is a difficult and traumatic time so it's challenging to say, 'You've got this traumatic illness and we want you to start treatment and go on this trial'," Dr Fidler said.
Two previous studies have used HDAC inhibitors to stimulate the reservoir, but the body did not kill infected cells, which is why the UK team is using the vaccine, developed at Oxford. Dr Frater said that if this vaccine did not work, a different combination might still be effective in future. .
Earlier this year, an HIV-positive baby was apparently cured in the US, while two men who had bone marrow transplants have stopped taking Aids drugs without the virus returning. They are the latest in a series of cases that have suggested HIV can be eliminated. The most famous was Timothy Ray Brown, whose HIV vanished after a bone marrow transplant for leukaemia.
Dr Frater said the apparent success of a variety of approaches had allowed normally cautious scientists to begin expressing hopes for a cure. "There's genuinely a sense of optimism."
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