Anti-Alcohol Drug Could Flush Out HIV

A drug commonly used to purge alcohol from the body may be used to flush HIV out of a patient's system, according to a new study published in The Lancet.

The study was conducted by a group of researchers on 30 patients from The Alfred Hospital in Melbourne and San Francisco General Hospital, between Sept 2013 and March 2014. It showed that short-term administration of disulfiram resulted in increases in cell-associated unspliced HIV RNA at all doses, consistent with activating HIV latency. Disulfiram may be suited for future studies of combination and prolonged therapy to activate latent HIV.

Disulfiram has been used for over 60 years to combat alcoholism by creating a sensitivity to alcohol, but recent lab tests have shown that the drug, along with others, can be used to find dormant reservoirs of HIV in cells that are reactivated when a patient stops ART, according to Medical Daily.�

Disulfirum is a well-tolerated drug with a long safety record, and could be used in a latency-reversing agent (LRA) in a "shock and kill" or "kick and kill" strategy to combat HIV. The strategy seeks to destroy HIV by "kicking" latent strains of HIV out of dormancy to make them more visible to the immune system. Then, using immunotherapy created from the patient's own virus, they hope to coax the immune system into better responding to the newly replicating HIV and "kill" it.�

These latency-reactivating agents (LRAs) have been considered the potential first part of a so-called "shock-and-kill" strategy for destroying the last vestiges of a HIV infection driven underground by ART.

It's hoped that drugs like disulfiram can first root out the infection from its hiding places and then other drugs can be used to eliminate it completely from the body. The currently existing ART drugs, while largely successful, aren't suited for that job unfortunately, so new treatments would need to be discovered or invented for the second part as well. It's also possible that the simple act of flushing out HIV may naturally provoke the immune system to step in and finish the job itself.

This short-term use of disulfirum was correlated with an increase in the appearance of HIV RNA, however it was unclear whether the results could be replicated outside a laboratory.�But no deaths occurred, and no serious adverse events were noted. Disulfiram was well tolerated at all doses.

Unfortunately, as exciting as this latest study may appear on the surface, there are certain caveats that have to be acknowledged. For one, while the earliest in-vitro experiments of these reactivating drugs showed great gains in awakening latent HIV, subsequent studies using samples of HIV-infected cells derived from actual patients have provided dramatically weaker results.

It's thought that while these drugs can certainly increase the amount of HIV in a person's system, it's only a partial revival as of now. Even with the current study, it's unknown whether the increase�in unspliced HIV RNA detected in their subjects amounts to a clinically significant reactivation.

The authors themselves note that disulfiram might be suited to being used as part of a combination of drugs, concluding that certain combinations of two latency-reversing agents (LRAs) may up their potency far past what any one drug can offer on its own. Though the combinations with disulfiram did not prove to be the most potent of those tested, it might be the safest for humans to regularly take, since there are concerns that other potential LRAs may be too toxic for human consumption.

"Our findings support further study of disulfiram combinations and consideration of future clinical testing," the authors of the May study concluded.

The study was funded by The Foundation for AIDS Research (amfAR); National Institute of Allergy and Infectious Diseases, National Institutes of Health; Australian National Health and Medical Research Council.