An interventional study of Disulfiram in HIV-1 Infection, sponsored by University of California, San Francisco. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-06-30.
Sponsored by University of California, San Francisco · Not applicable, Interventional, and Other
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.
University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: Disulfiram
Open label 500mg disulfiram per day by mouth for 14 days
Also known as: 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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Two weeks
| Milestone | Intervention Arm |
|---|---|
| Started | 16 |
| Completed | 16 |
| Not completed | 0 |
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.
| Fold change in IUPM | Intervention Arm |
|---|---|
| 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 | 1.16 (0.70 to 1.92) |
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.
| Participants | Intervention Arm |
|---|---|
| Number of Participants With Adverse Events | 0 |
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.
| Fold change | Intervention Arm |
|---|---|
| The Fold Change in Mean Levels of Viremia During and After Disulfiram Dosing as Compared to Baseline Levels | 1.5 (0.9 to 2.7) |
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.
| Participants | Intervention Arm |
|---|---|
| Number of Participants With Detectable Plasma HIV RNA | 1 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intervention Arm | — | 0/16 (0%) | 0/16 (0%) |
| Age, Continuous(years) | Intervention Arm |
|---|---|
| Mean | 47.5 (24 to 60) |
| Sex: Female, Male(Participants) | Intervention Arm |
|---|---|
| Female | 1 |
| Male | 15 |
| Region of Enrollment(participants) | Intervention Arm |
|---|---|
| United States | 16 |
This study is completed, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.
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University of California, San Francisco