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Romidepsin HDAC Inhibitor Stimulates
HIV from Reservoirs in Hunt to Find HIV Cure
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IAC: The HDAC inhibitor romidepsin is safe and effectively reverses HIV-1 latency in vivo as measured by standard clinical assays (07/22/14)
webcast
http://pag.aids2014.org/flash.aspx?pid=4968
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HIV research: Cancer drug breakthrough in ''kicking'' disease out of hiding place
Celgene drug can drive HIV out of hiding: study
· Jul. 22, 2014, 8:44 AM
By Kate Kelland
LONDON (Reuters) - An anti-cancer drug made by the U.S. biotech firm Celgene can re-activate hidden HIV in patients so that it can be detected, bringing researchers closer to being able to treat it, Danish scientists said on Tuesday.
In a small study presented at an international AIDS conference in Australia, the researchers said the finding was a "step in the right direction" toward finding a cure for the viral disease but that many years of research are still needed.
"There is still a long way to go and many obstacles to overcome before we can start talking about a cure against HIV," said Ole Schmeltz Sogaard, who led the research team from Aarhus University and Aarhus University Hospital in Denmark, in a statement.
The drug, known generically as romidepsin and under the brand name Istodax, is licensed to treat a type of cancer called T-cell lymphoma. In this study, however, it was investigated as a potential HIV therapy.
Human immunodeficiency virus (HIV) infection can be kept at very low levels by anti-AIDS drugs, but there is still no cure that can eradicate HIV from the body.
Some 35 million people worldwide are infected with HIV, and the global AIDS epidemic has killed 39 million since it began in the 1980s, according to the latest data from the United Nations AIDS program, UNAIDS.
Scientists working to find a cure know the virus can hide in a state of hibernation in cells called CD4 cells, which are part of the body's immune system.
CD4 cells cannot fight the AIDS virus themselves, but killer T-cells can if they are able to tell whether or not a CD4 cell contains the hibernating HIV.
Sharon Lewin, co-chair of the AIDS2014 conference in Melbourne Australia and a professor of infectious diseases who was not directly involved in this study, said the results of the study were significant and encouraging because they showed "we can wake up the virus reservoir and make enough of (it) to leave the cell, making it visible to an immune response".
The Danish team gave three once-weekly infusions of romidepsin to six HIV-positive adult patients who were already taking antiretroviral AIDS drugs and whose so-called "viral load" was undetectable.
They found that romidepsin increased the virus production in HIV-infected cells between 2.1 and 3.9 times above normal and that the viral load in the blood increased to measurable levels in five out of six patients.
"We have now shown that we can activate a hibernating virus with romidepsin and that the activated virus moves into the bloodstream in large amounts," Schmeltz Sogaard said in a statement about the results.
When the virus is activated and moves toward the bloodstream it leaves a trace on the outside of the infected CD4 cells, he explained. In principle, this means killer T-cells would be able to trace and destroy the HIV-infected CD4 cells.
The Danish team said the next step is a larger trial where the researchers will combine romidepsin activation of hidden HIV with an experimental vaccine called Vacc-4x being developed by the Norwegian biotech firm Bionor Pharma to strengthen the ability of T-cells to fight HIV.
(editing by Jane Baird)
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HIV research: Cancer drug breakthrough in ''kicking'' disease out of hiding place
http://www.smh.com.au/national/health/hiv-research-cancer-drug-breakthrough-in-kicking-disease-out-of-hiding-place-20140722-zvnke.html
July 22, 2014
Danish researchers have found a way to activate and expose hidden HIV cells to the immune system - a major step towards finding a cure for the virus affecting 38 million people.
Ole Sogaard, a doctor from Aarhus University Hospital in Denmark, said a study of six HIV-positive patients showed that a cancer drug could ''kick'' HIV out of its hiding place and into the bloodstream, where it can theoretically be attacked by the immune system.
The finding has been hailed the single most important advance reported at the 20th International AIDS conference in Melbourne, where thousands of the world's leading HIV experts have gathered to share their research.
Dr Sogaard said his team gave the patients three doses of the cancer drug romidepsin over three weeks to see if it would move the virus out of reservoirs where it hides and cannot be detected. All patients were long-term HIV patients who remained on their antiretroviral treatment for the trial.
He said before the drug was given to the patients, they had undetectable levels of HIV in their system. But within days of receiving the cancer drug, significant amounts of the virus had moved into their blood.
"We could see that within a very short time, one to three days, we could measure a large increase in the number of viral particles,'' he said.
"So these cells are going from being in a resting state to exposing themselves to the immune system."
Dr Sogaard said while the patients' immune systems did not destroy the virus, a new trial involving 20 patients would combine this "kick" approach with an experimental HIV vaccine (Vacc-4x) to see if it can stimulate a strong enough immune response to kill the virus.
But he said this may not work if the virus still persists in some hidden cells.
In his study, it was unclear whether all of the hiding cells had been deployed by the romidepsin or just some of them.
"We don't know if we did it for 1 per cent of the cells or 5 per cent or 50 per cent,'' he said. "All we can say is we did it at least for some of the cells ... so it is still early days.''
While at least one man known as the "Berlin patient" is believed to have been cured of HIV through a bone marrow transplant from a donor with a genetic mutation that protects a small number of people from HIV, doctors say this is not a practical solution for others mainly because transplants are dangerous and expensive and donors with genetic protection against HIV are rare.
Instead, most HIV researchers believe a "kick and kill" approach that ''wakes up" the virus to expose it to the immune system is a promising direction for cure research.
Dr Sogaard said while antiretroviral treatments stopped HIV from spreading throughout the body, the virus also hid in "reservoir" cells that were resistant to the treatment. This was the main barrier to curing people.
"Despite taking antiretroviral treatment for years, we know that once patients stop taking treatment, in a matter of about two weeks, there will be millions and millions of viral particles throughout the body. And the reason for this is the resting cells,'' he said.
"In theory, if you can activate all cells and expose them to the immune system and get them killed, then you have cured a person.''
Dr Sogaard said although some of the patients experienced fatigue and nausea - common side effects of the cancer drug - there was no immediate concern about the impact on their health.
Steven Deeks, a professor of medicine at the University of California who specialises in HIV research, said the Danish research was likely to have a huge impact on HIV cure research worldwide.
"Ole's data is the first clear evidence, at least to me, that we can truly identify the latent reservoir, the hidden virus, and shock it out of its hiding place," he said.
"I don't think anyone has shown that in people before to the same degree that Ole has in his study. I think actually it is the single most important advance of this meeting and it's going to have a huge impact in future."
Meanwhile, Corinne Treger, the chief executive of French pharmaceutical company Biosantech, said a phase two trial of a therapeutic vaccine to treat HIV, not prevent it, was showing some positive results.
If the experimental vaccine, known as "Tat Oyi", is proved to be safe and effective, she said people with HIV could receive several injections to control their virus permanently instead of taking antiretroviral treatment, which can have side effects and cost thousands of dollars a year.
Ms Treger said her company was collaborating with Canadian researchers testing "Immnunorex", an experimental drug hoped to treat and prevent cardiovascular diseases, dementia and cancers induced and enhanced by HIV, and prevent HIV mutations that lead to drug resistances and vaccine failure.
It is hoped this drug would be jointly administered with the Tat Oyi vaccine to improve the health of people living with HIV.
Ms Treger said of about 12 studies testing a therapeutic vaccine, her company's was the most advanced. If a new trial in 80 patients in 2015 goes well, she said the vaccine could be available in 2017.
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