Ciclopirox Eradicates HIV Permanently From Infected Cells

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 intimate
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.
http://www.sciencedaily.com/
releases/2013/09/130923200129.htm
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.
Drugs reactivate suicide pathway
in HIV-infected cells
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.
First study to show additional
route to cell suicide
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
http://www.medicalnewstoday.com/
articles/266683.php

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