Fungal Drug Forces HIV Suicide

Feb. 21, 2014

By Medical Discovery News

Fungal Drug Forces HIV Suicide

What do nail fungus and HIV have in common? As it turns out, the same drug may cure them both. A topical drug called Ciclopirox, commonly prescribed to treat nail fungus, has been found to kill HIV-infected cells in the lab.

The drugs that are currently used to treat HIV and prevent the progression to AIDS unfortunately do not eliminate the virus from the body. If people stop taking the drugs, the virus will rapidly take control. That means HIV-infected people have to stay on a combination of anti-retroviral drugs for the rest of their lives. Current combination drug therapies are very successful in controlling the virus and have made HIV a survivable disease. But many of the current HIV therapeutics have significant side effects including diarrhea, nausea, vomiting, and even damage to the liver and kidneys. They are also expensive, about $10,000-12,000 per patient per year in the U.S. It has long been a dream to find drugs that could eliminate the virus and cure HIV patients.

HIV is one member of a family of viruses called Lentiviruses. When these viruses infect someone, they enter host cells by binding to specific receptors on their surfaces. Once inside the cell, the virus’s genetic information is converted into DNA, the same type of molecule that human genes made of. The virus has an enzyme that inserts its genetic information into the genomes of the human cells. From that moment, that cell is infected for its life. Then the virus replicates and infects other cells.

Since the virus’s genetic information is now permanently lodged in the host cell’s genome, it is expressed and passed on to daughter cells if and when infected cells divide. That is why HIV-infected people must stay on anti-HIV medication for life. Without the medications the virus would replicate and eventually lead to immunodeficiency, progression to AIDS, and death. One of the defense mechanisms against viral infections is a pathway that allows a damaged or infected cell to commit suicide, thereby limiting the amount of viruses produced and spread. Unfortunately, HIV has evolved a mechanism to block this suicide pathway.

A research team from the New Jersey School of Medicine demonstrated that Ciclopirox, which is used by dermatologists and gynecologists to treat fungal infections, inhibits HIV gene expression. The drug also blocks an essential function of the infected host cells, reactivating the suicide pathway and leading to the death of HIV-infected cells, at least in lab cultures. Remarkably, when the drug was removed from the cultures, there was no resurgence of HIV, indicating the cultures no longer harbored the virus.

Before such a treatment can be applied to humans, a form of Ciclopirox that can be given systemically, such as a pill or shot that would apply the drug to cells throughout the body, must be developed. There are also other classes of drugs that may trigger the suicide of HIV-infected cells. Used in combination, this approach may offer for the very first time not only a treatment for HIV infection but possibly a cure.

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