Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals
University of California, San Francisco
Johns Hopkins University
Information provided by (Responsible Party)
University of California, San Francisco
First received: January 27, 2011
Last updated: October 28, 2014
Last Verified: October 2014
History of Changes
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).
Drug : Disulfiram
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|Official Title:||Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals|
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 ]
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 ]
|Study Start Date:||January 2011|
|Study Completion Date:||May 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Open label 500mg disulfiram per day by mouth for 14 days
Other Name: Antabuse
This study is using a new approach to try and force HIV out of its protected cellular
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.
|Ages Eligible for Study:||18 Years and older|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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 LocationsChoosing 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 Show More
|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 CollaboratorsUniversity of California, San Francisco
Johns Hopkins University
|Principal Investigator:||Steven G. Deeks, M.D.||University of California, San Francisco|
|Principal Investigator:||Adriana Andrade, M.D.||Johns Hopkins University|
|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|
Keywords provided by University of California, San Francisco:HIV
Additional relevant MeSH terms:
ClinicalTrials.gov processed this data on March 16, 2018
This information is provided by ClinicalTrials.gov.