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

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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

Tracking Information
First Submitted Date  ICMJE January 27, 2011
First Posted Date  ICMJE January 31, 2011
Results First Submitted Date  ICMJE November 6, 2018
Results First Posted Date  ICMJE June 30, 2020
Last Update Posted Date June 30, 2020
Study Start Date  ICMJE January 2011
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2011)
  • 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 ]
  • 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 ]
    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 ]
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals
Official Title  ICMJE Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals
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).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE Drug: Disulfiram
Open label 500mg disulfiram per day by mouth for 14 days
Other Name: Antabuse
Study Arms  ICMJE Experimental: Intervention Arm
Intervention: Drug: Disulfiram
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 28, 2014)
16
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2011)
20
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01286259
Other Study ID Numbers  ICMJE IRB 10-02648
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Johns Hopkins University
Investigators  ICMJE
Principal Investigator: Steven G. Deeks, M.D. University of California, San Francisco
Principal Investigator: Adriana Andrade, M.D. Johns Hopkins University
PRS Account University of California, San Francisco
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP