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

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01286259
First received: January 27, 2011
Last updated: October 28, 2014
Last verified: October 2014
  Purpose

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 Intervention
HIV-1 Infection
Drug: Disulfiram

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • To determine if the addition of disulfiram to a stable antiretroviral regimen for two weeks results in decline in the size of the HIV-1 reservoir, as defined by the frequency of resting CD4+ T cells harboring replication competent HIV-1. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • To determine if the addition of disulfiram to a stable antiretroviral regimen for two weeks is associated with an immediate or transient increase in plasma HIV-1 RNA levels. [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]
    Real time viral load will be measured weekly during the treatment phase.

  • To determine if the addition of disulfiram to a stable antiretroviral regimen for two weeks is safe and well tolerated. [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]
  • To determine if the addition of disulfiram to a stable antiretroviral regimen for two weeks results in an increase in the frequency of activated CD4+ and CD8+ T cells in peripheral blood. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: January 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention Arm Drug: Disulfiram
Open label 500mg disulfiram per day by mouth for 14 days
Other Name: Antabuse

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286259

Locations
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
Principal Investigator: Steven G. Deeks, M.D. University of California, San Francisco
Principal Investigator: Adriana Andrade, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01286259     History of Changes
Other Study ID Numbers: IRB 10-02648
Study First Received: January 27, 2011
Last Updated: October 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
HIV
HAART suppressed
Disulfiram
Antabuse
Latent reservoir
Eradication
Cure

Additional relevant MeSH terms:
Disulfiram
Alcohol Deterrents
Central Nervous System Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014