Drugs

Disulfiram

Disulfiram

Other Names: Antabuse, DSF, tetraethylthiuram disulfide Drug Class: Latency-Reversing Agents Molecular Formula: C10 H20 N2 S4 Registry Number: 97-77-8 (CAS) Chemical Name: Disulfide, bis(diethylthiocarbamoyl) Chemical Class: Thiuram disulfides Phase of Development: Disulfiram is in Phase I/II development as a latency-reversing agent for HIV.

(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group website,2 ChemMedChem article,3 and ClinicalTrials.gov4)

What is disulfiram?

What is disulfiram?

Disulfiram is a drug that has been approved by FDA for helping in the management of alcoholism. Disulfiram is also an investigational drug that is being studied as part of a strategy to cure HIV infection.4–8 Disulfiram belongs to a general group of HIV drugs called latency-reversing agents

To learn about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

How do latency-reversing agents work?

How do latency-reversing agents work?

Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that the virus can remain hidden and inactive (latent) inside certain cells of the immune system (such as resting CD4 cells) for many months or even years. The cells where latent HIV hides are known as the latent HIV reservoir. Because HIV in this latent state is inactive, the immune system cannot detect the virus, and the antiretroviral (ARV) drugs that are used to treat HIV have no effect on it.9–11

Latency-reversing agents work by drawing HIV out of its latent state within resting CD4 cells. Once the latent HIV is reactivated, the CD4 cells that harbor the virus are more likely to be recognized and killed by the body’s immune system or by ARV drugs. Researchers hope that the combined use of disulfiram and other HIV-fighting strategies, including ongoing antiretroviral therapy (ART), may fully eliminate HIV from the body.9–11 

To learn more, see the AIDSinfo What is a Latent HIV Reservoir? fact sheet.

Disulfiram is a latency-reversing agent.12 There are different types of latency-reversing agents. Disulfiram is a type of latency-reversing agent called a phosphatase and tensin homolog (PTEN) inhibitor.10,13

Which clinical trials are studying disulfiram?

Which clinical trials are studying disulfiram?

Study Name: NCT01286259
Phase
: Not available
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to look at the safety of disulfiram and to see whether disulfiram added to ART could reactivate and then reduce the amount of latent HIV.6,7

Study Name: NCT01944371
Sponsor: University of California, San Francisco 
Phase: I/II
Status: This study has been completed.
Location: United States and Australia
Purpose: The purpose of this study was to look at the safety and effects of different doses of disulfiram on reactivating latent HIV.4,5

For more details on the studies listed above, see the Health Professional version of this drug summary.
Other HIV-related studies on disulfiram have either been completed or are planned, including:

  • NCT01571466, a phase I study that evaluated a therapeutic vaccine given alone and in combination with disulfiram.14,15
  • NCT03198559, a phase I/II study that evaluated how well a combination of high-dose disulfiram plus another latency-reversing drug called vorinostat reactivates latent HIV. This study was suspended for review of adverse events reported by study participants.16

What side effects might disulfiram cause?

What side effects might disulfiram cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of disulfiram listed above.

NCT01286259:
In this pilot study, 1 participant withdrew from the study after 12 days of taking disulfiram. Side effects that occurred during the study were reported as being either mild or moderate in severity.6,7

NCT01944371:
In this Phase I/II study, side effects that were likely or definitely caused by disulfiram included dry mouth/bad taste in mouth, headache, nausea, drowsiness, and light headedness, most of which were mild in severity. Seven participants had an electrolyte imbalance in which the level of phosphate in the blood was too low (called hypophosphatemia). No participants stopped the study early.4,17

Other side effects associated with disulfiram are described in the FDA-approved Antabuse Full Prescribing Information.8

Information on possible side effects of disulfiram use in HIV-infected people is not complete. As testing of disulfiram continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying disulfiram?

Where can I get more information about clinical trials studying disulfiram?

More information about disulfiram-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: Disulfiram. https://chem.nlm.nih.gov/chemidplus/rn/97-77-8. Accessed July 30, 2018.
  2. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed July 30, 2018.
  3. Kulkarni RA, Stanford SM, Vellore NA, et al. Thiuram disulfides as pseudo-irreversible inhibitors of the lymphoid tyrosine phosphatase. ChemMedChem. 2013;8(9). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863632/. Accessed July 30, 2018.
  4. University of California, San Francisco. Short-term disulfiram administration to reverse latent HIV infection: a dose escalation study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 12, 2013. NLM Identifier: NCT01944371. https://clinicaltrials.gov/ct2/show/NCT01944371. Accessed July 30, 2018.
  5. Lee SA, Elliott JH, McMahon J, et al. Disulfiram reactivates latent HIV infection in a dose-dependent manner. Abstract presented at: 16th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy; May 26-28, 2015; Washington, DC. Abstract 11. http://regist2.virology-education.com/abstractbook/2015_4.pdf.
  6. University of California, San Francisco. Short-term disulfiram administration to accelerate the decay of the HIV reservoir in antiretroviral-treated HIV infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 27, 2011. NLM Identifier: NCT01286259. https://clinicaltrials.gov/ct2/show/NCT01286259. Accessed July 30, 2018.
  7. Spivak AM, Andrade A, Eisele E, et al. A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1–infected adults on antiretroviral therapy. Clin Infect Dis. 2014;58(6):883-890.
  8. Teva Women’s Health, Inc. Antabuse: full prescribing information, May 2017. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f0ca0e1f-9641-48d5-9367-e5d1069e8680. Accessed July 30, 2018.
  9. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096.
  10. Rasmussen TA, Tolstrup M, Winckelmann A, Østergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccines Immunother. 2013;9(4):790-799.
  11. National Institute of Allergy and Infectious Diseases (NIAID). Fact Sheet, dated March 20, 2017. HIV Viral Eradication. https://www.niaid.nih.gov/diseases-conditions/hiv-viral-eradication. Accessed July 30, 2018.
  12. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed July 30, 2018.
  13. Archin NM, Sung JM, Garrido C, Soriano-Sarabia N, Margolis DM. Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nat Rev Microbiol. 2014;12(11):750-764.
  14. Hospital Clinic of Barcelona. A double-blind Phase I study to evaluate the safety of the HIV-1 vaccine MVA-B in chronic HIV-1 infected patients successfully treated with HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2011. NLM Identifier: NCT01571466. https://clinicaltrials.gov/show/NCT01571466. Accessed July 30, 2018.
  15. Mothe B, Climent N, Plana M, et al. Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. J Antimicrob Chemother. 2015;70(6):1833-1842.
  16. The Peter Doherty Institute for Infection and Immunity. Combination latency reversal with high dose disulfiram plus vorinostat in HIV-infected individuals on ART (DIVA): a single arm clinical trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 14, 2017. NLM Identifier: NCT03198559. https://clinicaltrials.gov/ct2/show/NCT03198559. Accessed July 30, 2018.
  17. Elliott JH, McMahon JH, Chang CC, et al. Short-term disulfiram to reverse latent HIV infection: a Phase 2 dose escalation study. Lancet HIV. 2015;2(12):e520-e529.

Last Reviewed: July 30, 2018