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
|Condition or disease||Intervention/treatment||Phase|
|HIV-1 Infection||Drug: Disulfiram||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|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|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||May 2014|
|Actual Study Completion Date :||May 2014|
|Experimental: Intervention Arm||
Open label 500mg disulfiram per day by mouth for 14 days
Other Name: Antabuse
- 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.
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
|United States, California|
|San Francisco General Hospital|
|San Francisco, California, United States, 94110|
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21205|
|Principal Investigator:||Steven G. Deeks, M.D.||University of California, San Francisco|
|Principal Investigator:||Adriana Andrade, M.D.||Johns Hopkins University|