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Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01286259
Recruitment Status : Completed
First Posted : January 31, 2011
Results First Posted : June 30, 2020
Last Update Posted : June 30, 2020
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
The purpose of this study is to determine whether a two-week course of disulfiram will reduce the HIV-1 latent reservoir in patients on highly active antiretroviral therapy (HAART).

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Disulfiram Not Applicable

Detailed Description:

This study is using a new approach to try and force HIV out of its protected cellular reservoirs.

Although current therapies are effective at "killing" new viruses that are produced, they are unable to access the virus in cells which were infected before antiretroviral therapy began. HIV can remain "hidden" in a latent (or resting) form in these cells for many years. Since these infected cells can live for many years, they are thought to be the most important barrier to HIV eradication (or "cure").

Many experts believe that one way to attack latent or "hidden" HIV is to use a drug than can "turn on" the virus and hence force HIV-1 out of resting T cells. In a recent study done in the laboratory, disulfiram proved to be among the most effective drugs currently available that can reactivate latent HIV-1,

Our primary hypothesis is that disulfiram will reduce the latent reservoir of HIV-1 in patients on highly active antiretroviral therapy (HAART). Theoretically, disulfiram will force HIV to replicate (grow) and thus result in the death of the infected cell. Standard antiretroviral drugs should prevent new cells from becoming infected. The end result of this process is that the total amount of HIV in the body will decline over time.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals
Study Start Date : January 2011
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Disulfiram

Arm Intervention/treatment
Experimental: Intervention Arm Drug: Disulfiram
Open label 500mg disulfiram per day by mouth for 14 days
Other Name: Antabuse




Primary Outcome Measures :
  1. Impact of Two Weeks of Disulfiram, as Measured by the Fold Change in the Infectious Units Per Million Cells (IUPM) Between Baseline and Week 12 [ Time Frame: 12 weeks ]
    The size of the latent reservoir from each participant was measured by limiting dilution co-culture assay and reported as "infectious units per million cells" (IUPM).This assay measures the frequency of peripheral blood cells from which replication-competent HIV can be grown. The assay was performed at a baseline visit (two weeks before dosing began) and week 12 (10 weeks after the last dose). The primary outcome was the fold-change in IUPM before and after disufiram.

  2. Number of Participants With Adverse Events [ Time Frame: Two weeks ]
    The safety and tolerability of a two-week course of disulfiram was defined using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009). Details are available on the RSC website (http://rsc.tech-res.com/safetyandpharmacovigilance/). The number of adverse events and their grade was determined for each subject.

  3. The Fold Change in Mean Levels of Viremia During and After Disulfiram Dosing as Compared to Baseline Levels [ Time Frame: Baseline to Day 18 ]
    Residual viremia was measured using a singe copy assay (SCA) in plasma samples obtained at enrollment, Days -14, -7, 0, 2, 4, 7, 9, 11, 14, 16, and 18, and at weeks 3, 4, 8 and 12. The level of residual viremia measured by SCA prior to disulfiram (Days 14, 17 and 0), during treatment (Days 1 to 14) and after dosing (Days 16 and 18) was modelled using negative binomial regression, and reported as the mean fold-change during and after disulfiram as compared to that during the baseline period.

  4. Number of Participants With Detectable Plasma HIV RNA [ Time Frame: Two weeks ]
    Plasma HIV RNA levels were measured weekly using a commercial assay. The number of participants who had a detectable viral load (> 50 copies RNA/mL) was determined.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented continuous HAART for at least 18 months prior to study entry and on a stable regimen for at least 3 months prior to entry.
  • Documented undetectable HIV viral loads for at least one year. Intermittent isolated episodes of detectable low-level viremia "blips" (> 50 but < 500 copies RNA/mL) remain eligible.
  • Screening plasma HIV-1 RNA levels < 40 copies RNA/mL.
  • CD4 T-cell count above 200 cells/uL for 24 weeks prior to screen.
  • >90% adherence to therapy within the preceding 30 days.
  • Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
  • Willing to abstain from any alcohol during the two week period in which disulfiram will be administered and during the two week period immediately after disulfiram administration.

Exclusion Criteria:

  • Current alcohol use disorder or hazardous alcohol use as determined by clinical evaluation.
  • Current use of any drug formulation that contains alcohol or that might contain alcohol.
  • Current use of tipranavir.
  • Current use of maraviroc.
  • Current use of warfarin.
  • Intending to modify antiretroviral therapy in the next 27 weeks for any reason.
  • Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
  • Severe myocardial disease or coronary artery disease.
  • History of psychosis.
  • Clinically active hepatitis determined by the study physician; ALT or AST >3 x the upper limit of normal.
  • Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks.
  • Pregnant or breastfeeding women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01286259


Locations
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United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
University of California, San Francisco
Johns Hopkins University
Investigators
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Principal Investigator: Steven G. Deeks, M.D. University of California, San Francisco
Principal Investigator: Adriana Andrade, M.D. Johns Hopkins University
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01286259    
Other Study ID Numbers: IRB 10-02648
First Posted: January 31, 2011    Key Record Dates
Results First Posted: June 30, 2020
Last Update Posted: June 30, 2020
Last Verified: June 2020
Keywords provided by University of California, San Francisco:
HIV
HAART suppressed
Disulfiram
Antabuse
Latent reservoir
Eradication
Cure
Additional relevant MeSH terms:
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Disulfiram
Alcohol Deterrents
Acetaldehyde Dehydrogenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action