HIVPhase 1/2NCT01944371
Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
A Phase 1/2 study testing Disulfiram in people with HIV and Human Immunodeficiency Virus, run by University of California, San Francisco at 2 sites in 2 countries.
Trial summary
The purpose of this study is to determine the safety, pharmacology and bioactivity of disulfiram in antiretroviral treated HIV-infected adults. The investigators primary hypothesis is that 3 days of disulfiram will result in an increase in HIV transcription in CD4+ T-cells in patients on suppressive antiretroviral… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Human Immunodeficiency Virus
- What is being tested?
- Disulfiram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2013to May 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection
- Age 18 or older
- HIV plasma viral load <50 copies/ml for at least 3 years with at least one measurement per year and most recent viral load within 3 months of screening.
- Receiving combination antiretroviral therapy (at least 3 agents); subjects must be on a efavirenz-based or a ritonavir-based regimen
- Two CD4+ T cell counts greater than 350 cell/µl in the six months prior to screening
- Willing to abstain from any alcohol one day before, during the three day period in which disulfiram will be administered and the two week period immediately after disulfiram administration
Who cannot join
- Current alcohol use disorder or hazardous alcohol use
- Current use of any drug formulation that contains alcohol or that might contain alcohol, including the gelatin capsule and liquid formulations of ritonavir, ritonavir/lopinavir, amprenavir and fosamprenavir.
- Current use of tipranavir or maraviroc.
- Current use of zidovudine, stavudine or didanosine (as disulfiram potentially has potent irreversible inhibitory effects on mitochondrial metabolism and hence could exacerbate the toxicity of these drugs).
- Concurrent use of rivaroxaban ( a CYP3A metabolized medication) as the cytochrome P450 inhibitory effects of disulfiram on rivaroxaban are unknown.
- Current use of warfarin
Show all 23Show fewer
- Patients who are intending to modify antiretroviral therapy in the next 2 weeks for any reason.
- Serious illness requiring hospitalization or parental antibiotics within preceding 3 months
- A screening hemoglobin below 12.5 g/dL
- A screening TSH consistent with Hypothyroidism
- Significant renal disease or acute nephritis
- Significant myocardial disease or diagnosed coronary artery disease
- Significant respiratory disease
- History of psychosis, seizure disorder, abnormal electroencephalogram or brain damage with significant persisting neurological deficit.
- Clinically active hepatitis as evidenced by clinical jaundice or Grade 2 or higher liver function test abnormalities.
- Hepatic cirrhosis or decompensated chronic liver disease.
- Diabetes or current hypothyroidism.
- Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks.
- Recent exposure (within the preceding 8 weeks) to any vaccine.
- Pregnant or breastfeeding women. Women 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.
- Significant substance use, which in the opinion of the investigator, is likely to interfere with the conduct of the study.
- Prior or current use of disulfiram, vorinostat or other experimental agent used with the intent to perturb the HIV-1 viral reservoir
- Current use of an antiretroviral regimen which does not include either efavirenz or a protease inhibitor
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
San Francisco General Hospital
San Francisco, California, 94110
About this study
The purpose of this study is to determine the safety, pharmacology and bioactivity of disulfiram in antiretroviral treated HIV-infected adults. The investigators primary hypothesis is that 3 days of disulfiram will result in an increase in HIV transcription in CD4+ T-cells in patients on suppressive antiretroviral therapy (ART).
Read the detailed description
Combination antiretroviral therapy for HIV-1 infection can suppress viremia to below the detection limit in the vast majority of motivated individuals with access to these drugs. However, HIV-1 persists in a small pool of latently infected resting memory CD4+ T cells carrying integrated viral genomes. Although other reservoirs for HIV-1 exist, the general consensus among experts is that latent virus (HIV DNA in resting memory CD4+ T cells) is the primary barrier to HIV-1 eradication. A widely discussed approach for eliminating this viral reservoir requires reactivation of latent HIV-1. Disulfiram, an FDA-approved drug used to treat alcoholism was shown to activate HIV-1 gene expression in vitro, suggesting that activation of latently infected cells in vivo may occur. Our primary hypothesis is that the addition of disulfiram to a stable effective antiretroviral drug regimen will result in a dose dependent increase in HIV transcription in CD4+ T-cells in HIV-1 in patients on highly active antiretroviral therapy (HAART).
- Conditions
- HIV, Human Immunodeficiency Virus
- Being tested
- Disulfiram
- Keywords
- Latent reservoir
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Also called Antabuse,NDC 0093-5036-01
This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
| Study group | Role | What they receive |
|---|---|---|
| disulfiram 500mg | Experimental | 500mg disulfiram by mouth per day for 3 days Receives: Drug: Disulfiram |
| disulfiram 1000mg | Experimental | 1000mg disulfiram by mouth per day for 3 days Receives: Drug: Disulfiram |
| disulfiram 2000mg | Experimental | 2000mg disulfiram per mouth per day for 3 days Receives: Drug: Disulfiram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell-associated HIV RNA
Fold change cell-associated HIV RNA in Total CD4 T-Cells.
Measured: Baseline and 3 days
Secondary outcomes (2)
Plasma HIV RNA
Fold change in plasma HIV RNA levels from baseline through day 3
Measured: Baseline and 3 days
Proviral HIV DNA
Fold change in HIV DNA levels between Baseline and Day 30
Measured: Baseline and 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Monash University, amfAR, The Foundation for AIDS Research, National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Principal investigator, Steven Deeks, University of California, San Francisco
- Investigators
- Steven Deeks, MD, Principal investigator, University of Californa, San FranciscoJulian Elliott, MD, Principal investigator, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01944371
- Sponsor's protocol ID
- 13-10948
- Other IDs
- DAIDS-ES ID 11864, K24AI069994
- Status last verified
- Dec 2018
- First submitted
- 12 Sep 2013
- Last updated
- 5 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, Savic R, Roney J, Hoh R, Solomon A, Piatak M, Gorelick RJ, Lifson J, Bacchetti P, Deeks SG, Lewin SR. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015 Dec;2(12):e520-9. doi: 10.1016/S2352-3018(15)00226-X. Epub 2015 Nov 17.
PubMed 26614966
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
- ClinicalTrials.gov ID
- NCT01944371
- Acronym / sponsor ID
- 13-10948
- Conditions
- HIV, Human Immunodeficiency Virus
- Keywords
- Latent reservoir
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Monash University, amfAR, The Foundation for AIDS Research, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Sep 2013
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 17 Sep 2013 (estimated)
- Results
- Posted 5 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety, pharmacology and bioactivity of disulfiram in antiretroviral treated HIV-infected adults. The investigators primary hypothesis is that 3 days of disulfiram will result in an increase in HIV transcription in CD4+ T-cells in patients on suppressive antiretroviral therapy (ART).
Detailed description
Combination antiretroviral therapy for HIV-1 infection can suppress viremia to below the detection limit in the vast majority of motivated individuals with access to these drugs. However, HIV-1 persists in a small pool of latently infected resting memory CD4+ T cells carrying integrated viral genomes. Although other reservoirs for HIV-1 exist, the general consensus among experts is that latent virus (HIV DNA in resting memory CD4+ T cells) is the primary barrier to HIV-1 eradication. A widely discussed approach for eliminating this viral reservoir requires reactivation of latent HIV-1. Disulfiram, an FDA-approved drug used to treat alcoholism was shown to activate HIV-1 gene expression in vitro, suggesting that activation of latently infected cells in vivo may occur. Our primary hypothesis is that the addition of disulfiram to a stable effective antiretroviral drug regimen will result in a dose dependent increase in HIV transcription in CD4+ T-cells in HIV-1 in patients on highly active antiretroviral therapy (HAART).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| disulfiram 500mg | Experimental | Drug: Disulfiram500mg disulfiram by mouth per day for 3 days |
| disulfiram 1000mg | Experimental | Drug: Disulfiram1000mg disulfiram by mouth per day for 3 days |
| disulfiram 2000mg | Experimental | Drug: Disulfiram2000mg disulfiram per mouth per day for 3 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- HIV-1 infection
- Age 18 or older
- HIV plasma viral load <50 copies/ml for at least 3 years with at least one measurement per year and most recent viral load within 3 months of screening.
- Receiving combination antiretroviral therapy (at least 3 agents); subjects must be on a efavirenz-based or a ritonavir-based regimen
- Two CD4+ T cell counts greater than 350 cell/µl in the six months prior to screening
Key exclusion criteria (23 listed)
- Current alcohol use disorder or hazardous alcohol use
- Current use of any drug formulation that contains alcohol or that might contain alcohol, including the gelatin capsule and liquid formulations of ritonavir, ritonavir/lopinavir, amprenavir and fosamprenavir.
- Current use of tipranavir or maraviroc.
- Current use of zidovudine, stavudine or didanosine (as disulfiram potentially has potent irreversible inhibitory effects on mitochondrial metabolism and hence could exacerbate the toxicity of these drugs).
- Concurrent use of rivaroxaban ( a CYP3A metabolized medication) as the cytochrome P450 inhibitory effects of disulfiram on rivaroxaban are unknown.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DisulfiramAlso: Antabuse,NDC 0093-5036-01This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days. | Drug | disulfiram 1000mg, disulfiram 2000mg, disulfiram 500mg |
Primary outcome
Cell-associated HIV RNA
Time frame: Baseline and 3 days
Fold change cell-associated HIV RNA in Total CD4 T-Cells.
2 secondary outcomes
Plasma HIV RNA
Time frame: Baseline and 3 days
Proviral HIV DNA
Time frame: Baseline and 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26614966Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, Savic R, Roney J, Hoh R, Solomon A, Piatak M, Gorelick RJ, Lifson J, Bacchetti P, Deeks SG, Lewin SR. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV. 2015 Dec;2(12):e520-9. doi: 10.1016/S2352-3018(15)00226-X. Epub 2015 Nov 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Deeks, MD principal investigator
University of Californa, San Francisco
Julian Elliott, MD principal investigator
Monash University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Disulfiram in people with HIV and Human Immunodeficiency Virus, run by University of California, San Francisco at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cell-associated HIV RNA (time frame: Baseline and 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01944371, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2020.