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| Name | Class |
|---|---|
| Johns Hopkins University | OTHER |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention Arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Disulfiram | Drug | Open label 500mg disulfiram per day by mouth for 14 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven G. Deeks, M.D. | University of California, San Francisco | Principal Investigator |
| Adriana Andrade, M.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco General Hospital | San Francisco | California | 94110 | United States | ||
| Johns Hopkins University |
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| ID | Title | Description |
|---|---|---|
| FG000 | Intervention Arm | Disulfiram: Open label 500mg disulfiram per day by mouth for 14 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention Arm | Disulfiram: Open label 500mg disulfiram per day by mouth for 14 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The size of the latent reservoir from each participant was measured by limiting dilution co-culture assay two weeks before and ten weeks after disulfiram administration.. | Posted | Mean | 95% Confidence Interval | Fold change in IUPM | 12 weeks | Blood samples | Blood samples |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention Arm | Disulfiram: Open label 500mg disulfiram per day by mouth for 14 days |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven G. Deeks | University of California, San Francisco | (415) 476-4082 | Steven.Deeks@ucsf.edu |
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| ID | Term |
|---|---|
| D004221 | Disulfiram |
| ID | Term |
|---|---|
| D004050 | Ditiocarb |
| D013859 | Thiocarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
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| Two weeks |
| Baltimore |
| Maryland |
| 21205 |
| United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Disulfiram: Open label 500mg disulfiram per day by mouth for 14 days
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Two weeks |
|
|
|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | Fold change | Baseline to Day 18 |
|
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Two weeks |
|
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| 0 |
| 16 |
| 0 |
| 16 |
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| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D004220 | Disulfides |
| D013440 | Sulfides |
| D013457 | Sulfur Compounds |