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

NCT01286259 | Completed Results DMC

• 1 other identifier: IRB 10-02648
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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).

Conditions

HIV-1 Infection

Keywords

HIV; HAART suppressed; Disulfiram; Antabuse; Latent reservoir; Eradication; Cure

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  12 weeks

• Number of Participants With Adverse Events

  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.

  Two weeks

• The Fold Change in Mean Levels of Viremia During and After Disulfiram Dosing as Compared to Baseline Levels

  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.

  Baseline to Day 18

• Number of Participants With Detectable Plasma HIV RNA

  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.

  Two weeks

Study Arms (1)

Intervention Arm

EXPERIMENTAL

Drug: Disulfiram

Interventions

Disulfiram DRUG

Open label 500mg disulfiram per day by mouth for 14 days

Also known as: Antabuse

Intervention Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Johns Hopkins University: collaborator

Study Sites (2)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Interventions

Disulfiram

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Results Point of Contact

• Title: Steven G. Deeks
• Organization: University of California, San Francisco

Steven.Deeks@ucsf.edu

(415) 476-4082

Study Officials

• Steven G. Deeks, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Adriana Andrade, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2011
• First Posted: January 31, 2011
• Study Start: January 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 30, 2020
• Results First Posted: June 30, 2020

Record last verified: 2020-06

Locations

US (2)