Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
3 other identifiers
interventional
30
2 countries
2
Brief 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 therapy (ART).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 hiv
Started Sep 2013
Shorter than P25 for phase_1 hiv
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2013
CompletedFirst Submitted
Initial submission to the registry
September 12, 2013
CompletedFirst Posted
Study publicly available on registry
September 17, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2014
CompletedResults Posted
Study results publicly available
May 5, 2020
CompletedMay 5, 2020
December 1, 2018
8 months
September 12, 2013
December 8, 2018
April 23, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cell-associated HIV RNA
Fold change cell-associated HIV RNA in Total CD4 T-Cells.
Baseline and 3 days
Secondary Outcomes (2)
Plasma HIV RNA
Baseline and 3 days
Proviral HIV DNA
Baseline and 30 days
Other Outcomes (1)
Disufiram Pharmacokinetics
31 days
Study Arms (3)
disulfiram 500mg
EXPERIMENTAL500mg disulfiram by mouth per day for 3 days
disulfiram 1000mg
EXPERIMENTAL1000mg disulfiram by mouth per day for 3 days
disulfiram 2000mg
EXPERIMENTAL2000mg disulfiram per mouth per day for 3 days
Interventions
This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- 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.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of California, San Franciscolead
- Monash Universitycollaborator
- amfAR, The Foundation for AIDS Researchcollaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
Study Sites (2)
San Francisco General Hospital
San Francisco, California, 94110, United States
Alfred Hospital
Melbourne, 3004, Australia
Related Publications (1)
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.
PMID: 26614966DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Steven G. Deeks
- Organization
- University of California, San Francisco
Study Officials
- PRINCIPAL INVESTIGATOR
Steven Deeks, MD
University of Californa, San Francisco
- PRINCIPAL INVESTIGATOR
Julian Elliott, MD
Monash University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Medicine
Study Record Dates
First Submitted
September 12, 2013
First Posted
September 17, 2013
Study Start
September 1, 2013
Primary Completion
May 1, 2014
Study Completion
May 1, 2014
Last Updated
May 5, 2020
Results First Posted
May 5, 2020
Record last verified: 2018-12