A drug used to treat alcoholism - called disulfiram - could bring us closer to a cure for HIV, according to the results of a new study led by researchers from the University of Melbourne in Australia.
Study leader Prof. Sharon Lewin, of The Peter Doherty Institute for Infection and Immunity at Melbourne, and colleagues publish their findings in The Lancet HIV.
Disulfiram (brand name Antabuse) is a drug given to individuals with an alcohol use disorder to discourage them from drinking. It works by blocking an enzyme called dehydrogenase, which plays a role in metabolizing alcohol intake.
Inhibiting dehydrogenase causes acute sensitivity to alcohol; if patients consume alcohol while taking disulfiram, they will experience a number of unpleasant side effects, including headache, nausea, chest pain, vomiting, weakness, blurred vision, sweating and mental confusion.
Antiretroviral therapy (ART) is the primary treatment for HIV, involving a combination of at least three antiretroviral drugs that slow disease progression. While the treatment has led to reductions in HIV death rates worldwide, it is not a cure.
ART is unable to eliminate HIV from patients completely; the virus can lay dormant in cells, hiding from immune system attack.
But in their phase 2 clinical trial, the researchers found disulfiram helped "wake up" dormant HIV cells, allowing them to be destroyed - a "shock-and-kill" approach that researchers believe is key to curing the virus.
Disulfiram 'could be the game changer we need'
Numerous studies have investigated such an approach. In September, for example, Medical News Today reported on a study that suggested a class of drugs being tested for the treatment of cancer could rewaken dormant HIV cells.
- More than 1.2 million people in the US aged 13 and older have HIV
- Around 1 in 8 people with HIV in the US are unaware they are infected
- There are around 50,000 new HIV infections in the US every year.
However, Prof. Lewin and colleagues note that to date, the drugs trialed to reawaken latent HIV have produced toxic side effects - a major barrier to moving the shock-and-kill approach forward.
For their study - conducted in collaboration with researchers from the University of California-San Francisco - the team gave disulfiram to 30 HIV-positive patients in the US and Australia who were receiving ART.
Disulfiram was administered daily for 3 days. Patients received 500 mg of the drug on the first day, 1,000 mg on the second day and 2,000 mg on the third day.
The researchers found that the 2,000 mg dose activated dormant HIV in patients' cells without producing any toxic side effects.
"The dosage of disulfiram we used provided more of a 'tickle' than a 'kick' to the virus, but this could be enough," says Prof. Lewin. "Even though the drug was only given for 3 days, we saw a clear increase in virus in plasma, which was very encouraging."
Prof. Lewin adds:
"This trial clearly demonstrates that disulfiram is not toxic and is safe to use, and could quite possibly be the game changer we need."
First study author Dr. Julian Elliott, head of clinical research in the Department of Infectious Diseases at Monash University and Alfred Hospital in Australia, notes that waking dormant HIV is only the first step to eliminating it; they now need to find a way to destroy it.
"This is a very important step as we have demonstrated we can wake up the sleeping virus with a safe medicine that is easily taken orally once a day," he adds. "Now we need to work out how to get rid of the infected cell. A kick-start to the immune system might help. We have an enormous amount still to learn about how to ultimately eradicate this very smart virus."
MNT recently reported that the US Food and Drug Administration (FDA) have approved a single-tablet drug called Genvoya for the treatment of HIV.