Ciclopirox and Deferiprone: Promise in the Lab, but No Cure Yet
Two drugs approved for other uses inhibited HIV replication and triggered death of HIV-infected cells in laboratory tests, researchers reported this week. These findings suggest a potential new approach for eradicating the virus, but it will likely be years before it can be used as part of a practical cure strategy.
Hartmut Hanauske-Abel and Michael Matthews from Rutgers New Jersey Medical School and colleagues tested two related compounds, ciclopirox and deferiprone, in human embryonic stem cell cultures and in peripheral blood mononuclear cells (PBMCs) infected with HIV obtained from patients.
Ciclopirox is an ingredient in various products used to treat fungal infections such as athlete’s foot and vaginal yeast infection. Deferiprone (Ferriprox) is an oral chelating agent used manage iron overload in people with the blood disorder beta thalassemia.
For more than a decade Hanauske-Abel’s team has been studying a novel strategy for blocking HIV replication and its detrimental effects. Their latest findings, published in the September 23 edition of PLoS ONE, explain how this multi-pronged approach might one day contribute to viral eradication in people with HIV.
The researchers found that both ciclopirox and deferiprone interfere with HIV in multiple ways. First, the drugs block HIV gene expression, preventing production of new virus.
In acutely infected PBMCs, ciclopirox completely suppressed viral replication. In PBMCs with already established infection, adding the drug reduced virus levels to undetectable. Viral breakthrough did not occur during 30 days of treatment, and viral replication did not restart even 12 weeks after stopping the drug, leading the team to conclude that the reservoir of latent HIV was eliminated.
Second, the drugs disrupted HIV’s control over apoptosis, or cell suicide. Normally, virus-infected cells undergo programmed cell death, but HIV neutralizes this natural defense mechanism. Ciclopirox and deferiprone restored the normal cell suicide response in HIV-infected cells, a phenomenon the authors dubbed “therapeutic reclamation of apoptotic proficiency,” or TRAP.
Healthy uninfected cells, however, were minimally affected. The researchers tested 1% ciclopirox cream in vaginal tissue in mice, and saw no damage at concentrations high enough to suppress HIV.
Because ciclopirox and deferiprone are already approved for human use, they might be able to move through the drug evaluation process more quickly.
Coauthor Deepti Saxena and colleagues have already done a proof-of-concept Phase 1 clinical trial of deferiprone in a small number of people with HIV in South Africa, according to a press release issued by Rutgers. Findings have not yet been published, but the PLoS ONE article noted that a one-week course of deferiprone reduced HIV viral load as much as zidovudine (AZT or Retrovir), and the effect lasted for seven weeks after stopping treatment.
The next step, the researchers proposed, could be testing the antiretroviral activity of ciclopirox and deferiprone in HIV-positive people who are taking them for their approved indications.
“These drugs can block virus production and seem to cause the infected cells to self-destruct,” said HIV cure expert Sharon Lewin from Monash University in Melbourne. “Drugs that don’t just ‘shock’ but also ‘kill’ latently infected cells are what the field is currently searching for, so these drugs could be promising, but there’s plenty more work to do.”
Liz Highleyman is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.