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Tags: cancer | drug | AIDS | virus | hidden | HIV | romidepsin

Old Cancer Drug Rouses Hidden HIV for Treatment

Tuesday, 22 July 2014 08:30 AM EDT

AIDS researchers seeking to cure HIV with a one-two punch got an early hint the approach may work by successfully using an old cancer drug to kick the virus out of hiding in a pilot study in Denmark.
Researchers from Aarhus University gave the medicine romidepsin to six HIV-infected people in an effort to rouse the virus from the so-called reservoirs where it sleeps. It worked: Infusions of the drug woke the virus up and caused it to start reproducing, a step that may allow the immune system to clear it, according to results reported Tuesday at an International AIDS Conference in Melbourne.
Antiretroviral pills can keep the virus in check, but don’t eliminate it from hidden reservoirs deep within the body. Studies have shown that when patients stop taking their meds, the virus proliferates from the reservoirs, forcing them to resume treatment. Bionor Pharma ASA (BIONOR), based in Oslo, is studying romidepsin as part of a “kick-and-kill” approach to curing HIV in which romidepsin kicks HIV out of hiding before another drug called Vacc-4x would prompt the immune system to kill it.
“It’s still just another step toward something that may end up being a cure for HIV, so it’s a step in the right direction,” co-author Ole Schmeltz Sogaard, a senior researcher in the department of infectious diseases at Aarhus University Hospital, told reporters in Melbourne.
Well Tolerated
Romidepsin was used at a third of the normal cancer dosing, he said. Side effects were consistent with those known to occur with romidepsin and others in a class of compounds that interfere with the function of the enzyme histone deacetylase. No severe toxicity was observed and no dose reductions were necessary, Sogaard said in an e-mail.
Bionor announced successful completion of the pilot study in May, and said it would start enrolling patients during the second quarter for the second part of the study, in which HIV-infected people will receive Vacc-4x and three weeks of romidepsin, before stopping their anti-HIV treatment to see if the virus rebounds. Initial results from the second part of the trial may be ready in the first half, Bionor said Tuesday.
Bionor shares jumped as much as 13 percent and were 11 percent higher at 3.13 Norwegian kroner as of 9:32 a.m. in Oslo, giving the company a market value of 707 million kroner ($114 million).
A study in 2012 of another old cancer drug, Merck & Co.’s (MRK) Zolinza, showed that that drug too roused HIV within the reservoirs. Still, the response to romidepsin points to a more potent method of activating latent virus in a way that may allow the immune system to hunt down and kill infected cells.
The patients received three infusions of romidepsin, sold by Celgene Corp. as Istodax, over 14 days. The drug increased virus production in HIV-infected cells by 2.1 to 3.9 times more than normal, and increased the amount of virus to measurable levels in the blood of five patients, a sign that the “kick” part of the strategy is working.
Because the amount of HIV that sleeps in viral reservoirs isn’t known, the researchers have no way of knowing how much of the latent virus was flushed out by the drug, Sogaard said.
Celgene, based in Summit, New Jersey, is providing a free supply of romidepsin to Bionor under an agreement between the two companies.
Worldwide, 35 million people are living with HIV, the Joint United Nations Program on HIV/AIDS estimated last week. Of those, 13.9 million are on antiretroviral therapy.
'Serious Challenges'
Over the last few years, academic teams around the world and drugmakers including Merck, Gilead Sciences Inc. (GILD) and Johnson & Johnson (JNJ) have been looking for ways to wipe out hidden reservoirs of the virus.
“We have always thought that once the virus gets inside a cell and goes to sleep, it’s stuck there forever,” said Sharon Lewin, the AIDS conference’s co-chair, who heads a team of researchers pursuing a cure for HIV at Melbourne’s The Alfred Hospital. Bionor’s results are “the first step to get rid of these long-lived, sleeping forms of virus with a drug that’s more potent than other drugs we have used already to wake up the virus. That’s a big step.”
Still, “serious challenges” lie ahead in the pursuit of a cure, said Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases.
“We do need a cure; it’s important,” Fauci said in an interview at the Melbourne AIDS meting. “But we might not get it. What we might get is a sustained virological remission of varying degrees of duration in different subsets of people.”
Cure research is still in the very early discovery phase, he said.
“There is a lot of enthusiasm,” Fauci said. “It’s certainly an aspirational goal that we should strive for. We have to be careful that we don’t make assumptions that we know the pathway to a cure and all we need to do is implement it.”

© Copyright 2023 Bloomberg News. All rights reserved.

AIDS researchers seeking to cure HIV with a one-two punch got an early hint the approach may work by successfully using an old cancer drug to kick the virus out of hiding in a pilot study in Denmark. Researchers from Aarhus University gave the medicine romidepsin to six...
cancer, drug, AIDS, virus, hidden, HIV, romidepsin
Tuesday, 22 July 2014 08:30 AM
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