Sep. 23, 2013 — The topical anti-fungal drug Ciclopirox causes HIV-infected cells to commit suicide by jamming up the cells' powerhouse, the mitochondria -- according to a study by researchers at Rutgers New Jersey Medical School. And unlike current anti-HIV drugs, Ciclopirox completely eradicates infectious HIV from cell cultures, with no rebound of virus when the drug is stopped. The study has been published in the journal PLOS ONE.

The treatment of patients with HIV has been revolutionized by the advent of combination anti-retroviral drugs. But although these drugs are highly effective at keeping HIV at bay, they must be taken for the life of the patient and never eliminate the infection completely. This is illustrated by the often rapid resurgence of virus in patients who stop taking these medications. The persistence of HIV is partially due to the ability of the virus to disable the cell's altruistic suicide pathway, which is normally activated when a cell becomes infected or damaged.

A team of researchers from three departments at New Jersey Medical School, led by Michael Mathews and Hartmut Hanauske-Abel, previously showed that Ciclopirox, commonly used by dermatologists and gynecologists to treat fungal infections, inhibits the expression of HIV genes in culture. The group now shows that the drug works against HIV in two ways: It inhibits the expression of HIV genes and also blocks the essential function of the mitochondria, thereby reactivating the cell's suicide pathway. Healthy, uninfected cells examined during this study were spared. And remarkably, the virus did not bounce back when Ciclopirox was removed.

The utility of Ciclopirox in patients with HIV, for instance after topical application to reduce sexual transmission of the virus, awaits verification in future clinical trials. However the fact that Ciclopirox is already approved for treatment of patients by the FDA and by its European counterpart, the EMA, and therefore considered safe for human use, may eliminate much of the time and expense ordinarily involved in the drug development process.

Indeed, the authors note the speed with which a second FDA-approved drug believed to have promise in subduing HIV, Deferiprone, has moved directly from tests in culture to a phase I human trial conducted in South Africa, thanks to previously published results now reinforced by additional research in culture described in the current paper. Studies in animals were safely skipped, creating a model for rapid transition from drug effect in a plastic dish to drug effect in patients. In contrast to Ciclopirox, approved for topical use, Deferiprone is FDA- and EMA-approved for systemic use (in certain thalassemia patients with iron overload). The discovery that two drugs, each well-tolerated by patients when used as indicated, are deadly to HIV-infected cells, may open a new chapter in the fight against HIV/AIDS that moves the world closer to the eradication of HIV-1 infection.

New research by an international team finds that Ciclopirox, an antifungal cream used all over the world, completely eradicates HIV - the virus that leads to AIDS - in cultured cells, and the virus does not return when the treatment stops.

The study also found Deferiprone, a systemic drug used to remove excess iron from the body in people who have beta-thalassaemia major, has the same effect.

The researchers, including a team from Rutgers New Jersey Medical School, write about their findings in a paper published online this week in the journal PLOS ONE.

As both drugs are already approved for use in humans - both in the US and Europe - the researchers say this means the normally lengthy process of drug development should be less costly and time-consuming, bringing closer the prospect of global elimination of HIV and AIDS.

[size=14pt]Drugs reactivate suicide pathway in HIV-infected cells[/size]

Viruses thrive by invading cells and using their resources. The cells of our body have a natural way of stopping this - they kill themselves. When the immune system detects the presence of a virus, it triggers a cell process called apoptosis that makes infected cells commit suicide.

But the human immunodeficiency virus (HIV) has a way around this: it disables the host cell's ability to commit suicide, allowing it to continue to exploit cellular resources to fuel its growth and spread.

In this new study, the researchers found the drugs work against HIV in two ways: they inhibit expression of certain HIV genes, and they also jam up the host cell's mitochondria, the little powerhouses that supply them with energy. Both these effects reactivate the cell's suicide pathway.

Healthy cells not infected with HIV were not affected. And remarkably, the virus did not bounce back when treatment stopped.



[size=14pt]First study to show additional route to cell suicide
[/size]
While previous research has already found Ciclopirox and Deferiprone can stop HIV by inhibiting some of the virus' genes, this new study is the first to show an additional route to reactivation of cell suicide via mitochondrial interference.

Thanks to these previous results confirmed in this new study, and the fact the systemic drug is already known to be safe in humans, testing the effectiveness of Deferiprone against HIV has already moved directly from cell culture to human trial in South Africa, bypassing the need for animal testing.

Ciclopirox is not approved for systemic use, as it is a topical cream. But the discovery that both drugs, each well-tolerated in humans, are also able to eradicate HIV in cell culture renews hope that HIV and AIDS will one day, in the not too distant future, be wiped from the face of the Earth.

The findings follow other good news released this week - as world leaders meet at the United Nations General Assembly to review progress towards the Millennium Development Goals, UNAIDS reports a 52% reduction in new HIV infections among children and a combined 33% reduction among adults and children since 2001.

Written by Catharine Paddock PhD

dominique: An anti-fungal drug to treat a viral infection? how come nobody thought about that An HIV cell does not have mitochondria except they're talking about the mitochondria of the host cell. Bogus research imo.

The topical anti-fungal drug Ciclopirox causes HIV-infected cells to commit suicide by jamming up the cells' powerhouse, the mitochondria

and they also jam up the host cell's mitochondria

Mr Troll:





both these quotes are found in the article...

as for an anti-fungal drug treating a viral infection...all I can think of now is Metronidazole

dominique:

That's an anti-biotic. I'm I missing somerhing here

Mr Troll: The findings follow other good news released this week - as world leaders meet at the United Nations General Assembly to review progress towards the Millennium Development Goals, UNAIDS reports a 52% reduction in new HIV infections among children and a combined 33% reduction among adults and children since 2001.

venorite: hmmmmmmmmm.....dis 1 is STRONG

dominique:

That's an anti-biotic. I'm I missing somerhing here