The 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 to treat fungal infections of the nails, 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 this drug in patients with HIV awaits verification in future clinical trials. However the fact that the drug is already FDA-approved for treatment of fungal infection, and therefore considered safe for human use, may eliminate much of the time and expense ordinarily involved in the clinical trial 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 trials in culture to phase I human trials, thanks to previously published results now reinforced by additional research in culture described in the current paper. This positive experience with Deferiprone is seen as a model for expediting research on other potential treatments for HIV/AIDS, including Ciclopirox.
Source: Rutgers Biomedical and Health Sciences