Published Thu, Mar 08, 2012 03:36 PM
Modified Thu, Mar 08, 2012 03:36 PM
By Jay Price - jprice@newsobserver.com
CHAPEL HILL -- Researchers at UNC-Chapel Hill have discovered what could be a vital step toward a cure for HIV.
By giving patients a drug normally used for treating some kinds of lymphoma, scientists have managed to make dormant, hidden HIV viruses reveal their presence.
That’s crucial if scientists want to find a way to target and completely eliminate the virus from the body, said Dr. David Margolis, a professor of medicine, microbiology and immunology, and epidemiology, who led the study.
Margolis spoke by telephone this afternoon from Seattle, just before presenting the findings at the 19th Conference on Retroviruses and Opportunistic Infections.
HIV is the virus that causes AIDS. In recent years, patients have been able to hold it at bay with elaborate cocktails of antiretroviral drugs.
Even though these regiments halt the progress of the disease, the virus remains, hiding in certain cells, and can turn active again if the drug regimen ends.
Researchers thought that a crucial step toward purging the body of HIV was finding a trigger to luring the virus from its hiding place. That’s what the UNC team did, for the first time.
The next steps in the research include a fuller exploration of the lymphoma drug’s effects on the virus, Margolis said.
The findings from that research will determine the next directions for research.
AIDS Cure Quest Advances as Merck Cancer Drug Attacks Hidden HIV
By Simeon Bennett - Mar 8, 2012 3:00 PM ET
The 30-year quest for an AIDS cure advanced as scientists succeeded for the first time in attacking HIV in its hardest-to-reach hideouts with a cancer drug made by Merck & Co.
In a trial among six men with HIV, researchers led by David Margolis at the University of North Carolina at Chapel Hill used a dose of Merck’s Zolinza to rouse the virus from inside certain immune-system cells, where it evades regular AIDS drugs. That’s a crucial step toward eliminating the virus from the body. The findings were presented at a conference in Seattle today.
While no patients were cured, the trial shows that Zolinza, or similar drugs, may have the potential to purge the virus, Margolis said. He said he expects to hear from the U.S. Food and Drug Administration within “a couple of weeks” on approval for an additional test using more doses of Zolinza.
“What people want to know is when can someone go to a doctor and be handed a pill and be cured,” Margolis said by phone. “That’s decades away. Think of it more in terms of curing cancer. I think in 10 years someone with HIV infection could go to a specialist and get a complicated treatment and have some likelihood of a prolonged remission of their HIV.”
Mysterious Virus
HIV was first observed in the U.S. as a mysterious, deadly illness among gay men in 1981. Since then it’s killed more than 30 million people globally, making it the world’s deadliest infectious disease.
The hunt for a cure has gathered pace because of improvements in the drugs used to control HIV, such as Gilead Sciences Inc. (GILD)’s once-daily pill Atripla, the world’s top-selling AIDS treatment.
While those drugs reduce HIV to undetectable levels in the body, they don’t completely clear it. The virus hides in certain cells, where it switches off the normal process of replication. That enables HIV to avoid detection by the medicines, which are designed to block steps in its reproduction.
Studies have shown that when patients who have the virus under control stop treatment, latent HIV reactivates and comes roaring back, forcing victims to resume daily pill therapy.
“It’s sort of like the virus is a rabbit at the bottom of a hole, but it needs a boost to get it out of the hole,”Margolis said. “It doesn’t fall in the hole very much, but when it does, it’s stuck there.”
Fine Line
Margolis and colleagues have been looking for ways to reactivate the virus without switching on the so-called resting CD4 T-cells in which it’s hiding. Arousing those cells may trigger a dangerous over-stimulation of the immune system that can cause lasting damage.
In the trial, the researchers recruited volunteers who were taking AIDS drugs to subdue the virus, then added Zolinza to see if they could reactivate latent HIV. It worked, with no serious side effects. The scientists saw an average 4.8-fold increase in HIV’s genetic fingerprints, showing the virus was awake and active inside the cells.
In theory, that means the drug has kick-started HIV’s normal process of replication. That could spur an immune-system attack that kills the host cells, or result in the virus exiting and killing the cells in search of new ones to infect. AIDS drugs patrolling the body would prevent it from doing so, and with nowhere left to go, the virus would die.
If that were to happen on a large enough scale, most latent HIV could be eradicated, enabling patients to stop their regular treatment without the virus rebounding -- a cure.
Next Trial
The study wasn’t designed to see whether Zolinza depleted the number of CD4 cells harboring HIV because the doses of the drug were too low, Margolis said. That’s the objective of the next trial now being considered by the FDA.
“We need to make some progress, we need some signal that we can potentially alter or disturb latently infected cells, and this study suggests that might be possible,” said Sharon Lewin, a professor at The Alfred Hospital in Melbourne. She’s also running a trial using multiple doses of Zolinza to target latent HIV and expects to have results from 10 patients later this year, she said.
Zolinza, also known as vorinostat and SAHA, was approved in 2006 for use against a rare type of blood cancer. The drug earned Merck $15 million in 2008, the last year the Whitehouse Station, New Jersey-based company disclosed sales of the medicine. Laboratory tests had shown it could purge HIV from cells in dishes, but the real challenge was to achieve the same result in humans.
“The study gives us hope because it provides an idea that’s worth exploring further,” said Daria Hazuda, Merck’s head of infectious diseases research, and one of the main developers of Isentress, an AIDS drug that generated $1.36 billion for Merck last year. “It’s a very important first step, but we’re still a long way away,” Hazuda said by telephone today.
Forcing Replication
The drug targets an enzyme called histone deacetylase, or HDAC, that helps HIV go to sleep in cells by interfering with its ability to replicate. By blocking HDAC, Zolinza would reactivate the virus, forcing replication.
This is Margolis’s second attempt at flushing out latent HIV. In 2005 he published a paper in The Lancet journal showing that Depakote, an approved treatment for bipolar disorder made by Abbott Laboratories, reduced the number of infected resting cells by as much as 84 percent when combined with Roche Holding AG’s AIDS drug Fuzeon, in a study involving four patients. Subsequent research by Margolis and others contradicted those findings.
Today’s results, the first to show that a mechanism known to keep HIV dormant could be successfully targeted in humans, were presented at the Conference on Retroviruses and Opportunistic Infections in Seattle.
To contact the reporter on this story: Simeon Bennett in Geneva at sbennett9@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
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