17 Nov 2015
Alcoholism drug breakthrough in waking up dormant HIV
Disulfiram, a drug used to treat alcoholism, could be a `game changer` in the pursuit of a non toxic drug capable of activating hidden HIV in the body, a key strategy on the path to finding a cure for HIV, according to a clinical trial conducted by researchers at the Peter Doherty Institute for Infection and Immunity and The Alfred in Melbourne, Australia, together with researchers from University of California San Francisco, USA, and published in The Lancet HIV today. (1)
Disulfiram was given to 30 HIV positive participants on suppressive antiretroviral therapy (ART) at increasing doses over a three-day period in Melbourne and San Francisco, and when given at the highest dose, there was evidence that dormant HIV was activated but with no adverse effects.
HIV latency, where the virus remains dormant in the body in people taking ART, is one of the biggest hurdles to curing HIV. ‘Waking up’ the virus in these dormant cells and then destroying the cell is a key HIV cure strategy, but finding the exact combination of drugs required remains elusive.
The leader of the international study team, Director of the Doherty Institute and a world leader in cure research and clinical management of HIV, University of Melbourne Professor Sharon Lewin, said that while scientists have been making headway into activating latent HIV, one of the barriers had been the toxicity of the drugs trialed to date.
“This trial clearly demonstrates that disulfiram is not toxic and is safe to use, and could quite possibly be the game changer we need,” she said.
“The dosage of disulfiram we used provided more of a ‘tickle’ than a ‘kick’ to the virus, but this could be enough. Even though the drug was only given for three days, we saw a clear increase in virus in plasma, which was very encouraging.”
First Author on the paper, Head of Clinical Research in the Department of Infectious Diseases at The Alfred, Dr Julian Elliott, said the results from the study were very promising and will now inform the design of further studies to find a way to possibly cure HIV.
“The next step is to get these cells to die. Waking up the virus is only the first step to eliminating it,” he said.
“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. 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.”
Professor Steven Deeks from the University of California San Francisco, a collaborator on the trial in the USA said, “Most groups are seeking for a powerful weapon to shock the virus out of its hiding place. These approaches may prove to be harmful.
“I see disulfiram as a more gentle way to accomplish this same goal, particularly if we can show it works when given over a long period of time.”
The trial was funded by the American Foundation for AIDS Research (amfAR), National Institute of Allergy and Infectious Diseases and National Institutes of Health in the USA and Australia’s National Health and Medical Research Council. The study team included investigators from Melbourne, University of California San Francisco, Johns Hopkins University and Frederick National Laboratory in the USA.
Approximately 34 million people have died due to HIV-related causes worldwide. By the end of 2014, there were an estimated 36.9 million people living with HIV globally, with approximately two million people becoming newly infected with the virus. (2)
(1) Short-term Disulfiram to Reverse Latent HIV Infection: A Phase 2 Dose Escalation Study, Lancet HIV, November 16, 2015
(2) UNAIDS AIDS Info 2014