A drug commonly prescribed to treat nail fungus appears to come with a not-so-tiny side effect: killing HIV in cell cultures.
In a study performed at Rutgers New Jersey Medical School, not only does the drug Ciclopirox rid infectious HIV from cell cultures, but the virus also doesn't bounce back when the drug is withheld.
The same group of researchers had previously shown that Ciclopirox -- approved by the FDA and Europe's EMA as safe for human use to treat foot fungus -- inhibits the expression of HIV genes in culture. Now they have found that it also blocks the essential function of the mitochondria, which results in the reactivation of the cell's suicide pathway, all while sparing the healthy cells.
The researchers said that one aspect of HIV that makes it particularly persistent, even in the face of strong antiviral treatments, is its ability to disable a cell's altruistic suicide pathway -- which is typically activated when a cell is damaged or infected. In other words, infected cells that would normally commit suicide to spare healthy cells no longer pull any altruistic kamikaze missions. Ciclopirox tricks these cells back into their old ways with a double negative, disabling the disabling of the suicide pathway.
"The key thing these drugs do is, unlike anti-retrovirals in the current clinical arsenal, and there are lots of them and they have controlled this disease pretty successfully, these drugs kill the HIV-infected cell," says Michael Matthews, lead researcher and chair of the school's department of biochemistry and molecular biology. "That's what's so new and so promising about it."
It's obviously still going to take clinical trials on humans to study the safety and efficacy of Ciclopirox as a potential topical HIV treatment, but the fact that it's already deemed safe for one type of human use could make the regulatory process faster than usual.
Unfortunately, says Dr. Robert Gallo, a professor of medicine at the University of Maryland best known for co-discovering HIV in 1984, even if the topical antifungal treatment successfully kills HIV-infected cells in clinical trials, it would need to be a systemic treatment, not a topical one, to actually treat (instead of simply prevent) HIV.
"On the positive side, I know Mike Matthews, and he's a superb scientist, probably the lead guy on this," says Gallo, who did not participate in this research. "And that is exciting that it kills cells. That would be very exciting if you could give it systemically and it kills only HIV-infected cells. But topical treatment would be for prevention, not as a therapy. The only way you could use it as a therapy is systemically, and it would be unlikely this could be used systemically."
But Rutgers researcher Hartmut Hanauske-Abel, who is working with Matthews, says that the topical treatment may some day be used systemically, and that Ciclopirox "must no longer be considered a topical-only drug."
The researchers also note that another FDA-approved drug now thought to help subdue HIV, called Deferiprone, skipped studies in animals and went straight from tests in culture to a phase I human trial in South Africa, possibly paving the way for other FDA-approved drugs to move faster through the study phases. (Unlike Ciclopirox, which is approved for topical treatment, Deferiprone is FDA- and EMA-approved for systemic use.)
The new findings on Ciclopirox appear in the current issue of the journal PLOS ONE.
Update, September 26 at 1:47 p.m. PT: The headline and lead paragraphs have been changed to clarify what the study found. Also this story has been updated with comments from Michael Matthews, Hartmut Hanauske-Abel, and Robert Gallo.