Reversing latent HIV infection with disulfiram

Disulfiram (D3374) is an acetaldehyde dehydrogenase inhibitor that prevents alcohol metabolism and is used to treat chronic alcohol dependence. Disulfiram has been used for this purpose for many decades. Recently, a strong movement is in place to find new indications for already-marketed compounds. Finding new uses for compounds that are already marketed allows for quicker advancement through pre-clinical and clinical work, as much of the required safety data is already available.

Disulfiram is one of the many compounds that have experienced resurgences in research studies going beyond their initial usage. In an article published in Lancet HIV, disulfiram was shown to have effects in HIV models. One challenge with HIV treatment is that latent (dormant) virus is often difficult to remove, as many current therapies focus on preventing replication or entry of active viral particles but are not effective against the virus in its latent form. In this study, short-term administration of disulfiram activated HIV transcription and increased plasma HIV RNA in a clinical setting.

Disulfiram may therefore show benefit when combined with current HIV therapies as it may “flush out” and induce activation of latent virus, allowing antivirals to attack more effectively.

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For more information on the original study, click here.

References:

Elliott JH, McMahon JH, Chang CC, et al. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015 Dec;2(12):e520-9. PMID: 26614966.