Phase 2
Completed N=30
Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
Source: ClinicalTrials.gov NCT01944371 ↗Enrolled (actual)
30
Serious AEs
0.0%
Results posted
May 2020
Primary outcomePrimary: Cell-associated HIV RNA — 1.7; 1.9; 1.6 Fold change
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cell-associated HIV RNA |
1.7; 1.9; 1.6 | — |
| SECONDARY Plasma HIV RNA |
1.50; 0.90; 1.22 | — |
| SECONDARY Proviral HIV DNA |
1.07; 0.83; 0.91 | — |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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.
- 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
Data sourced from ClinicalTrials.gov (NCT01944371). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.