It could be just what HIV researchers the world over have been waiting for – a non-toxic drug that will drive the virus from its hiding places around the body. What is it? The well-known anti-alcohol drug, Antabuse. The drug, also called disulfiram, has been given to alcoholics for decades, making them vomit if they drink at the same time – a strong disincentive. But now a small clinical trial suggests this drug also flushes out dormant HIV from its hiding places in infected people. If bigger trials support the finding, the drug could be a vital step towards a cure for HIV. Today’s antiretroviral drugs are powerful enough to eradicate HIV from the blood, but the virus can hide in a dormant state elsewhere in the body, and re-emerge if a person stops taking these drugs. As a consequence, people with HIV have to stay on these drugs for the rest of their lives.
One strategy would be to somehow wake up the dormant virus, flushing it from its hiding places so that it can be killed off once and for all. For this “kick and kill” strategy to work, drugs are needed to prod the virus into life. Viral activity Until now, the main candidates have been a class of drugs called histone deacetylase inhibitors, but these have too many toxic side effects to be a realistic option. Disulfiram, by contrast, can be given harmlessly for long periods – as long as people avoid alcohol. “Disulfiram is very safe and can easily be given for weeks or months,” says Sharon Lewin of the University of Melbourne, Australia, whose team has tested the drug on 30 people with HIV over a period of three days. Over that time, they found an increase in HIV gene expression in all of their study group. The researchers think this is a sign that dormant virus had been woken up, although they can’t yet be sure if dormant cells are responsible. Kick and kill Disulfiram alone won’t do the trick, but it is a promising candidate for combining with other drugs, says Asier Sáez-Cirión of the Pasteur Institute in Paris. With a “kick and kill” strategy a second drug would be needed to kill the reawakened virus, either completely curing a person, or reducing the virus to such a low level that their own immune system can keep it under control, without the need for antiretroviral drugs. “Having the virus there but at low levels would itself be a great outcome,” says Lewin. The team is now hunting for a suitable second drug because current antiretroviral drugs do not kill infected cells, they only prevent the virus from infecting new ones. Lewin says the hope is that disulfiram and a second drug could be given over a finite period, and then a person could be healthy and drug-free. Although other approaches have seemingly cured HIV before, these have so far all ended in disappointment when the virus bounced back after being undetectable. Journal reference: The Lancet HIV, DOI: 10.1016/S2352-3018(15)00226-X
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