Ученые: препарат от рака позволит "извлечь" ВИЧ из внутренних резервуаров организма
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 today 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.
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.
Celgene Corp. (CELG)
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.
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.”