disulfiram and HIV Coinfection studies

Research Excerpts

Excerpt	Relevance	Reference
"A 43 year old man with HIV and HCV infection and liver cirrhosis developed fatal lactic acidosis within five days from starting nifedipine for arterial hypertension."	7.75	Fatal lactic acidosis precipitated by nifedipine in a patient treated with disulfiram and antiretrovirals. ( Mian, P; Moling, O; Pagani, L; Pristerà, R; Rimenti, G; Spoladore, G; Vedovelli, C, 2009)
"A 43 year old man with HIV and HCV infection and liver cirrhosis developed fatal lactic acidosis within five days from starting nifedipine for arterial hypertension."	3.75	Fatal lactic acidosis precipitated by nifedipine in a patient treated with disulfiram and antiretrovirals. ( Mian, P; Moling, O; Pagani, L; Pristerà, R; Rimenti, G; Spoladore, G; Vedovelli, C, 2009)
"MVA-B was safe and well tolerated."	2.80	Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. ( Alcamí, J; Alvarez-Fernández, C; Arnaiz, JA; Benito, JM; Blanco, J; Brander, C; Carrillo, J; Climent, N; Clotet, B; Esteban, M; García, F; García-Arriaza, J; Gatell, JM; Gómez, CE; Gonzalez, N; Guardo, AC; Jiménez, JL; León, A; López Bernaldo de Quirós, JC; Martinez-Picado, J; Mothe, B; Muñoz-Fernández, MÁ; Peña, J; Perdiguero, B; Pich, J; Plana, M; Puertas, MC; Rallón, N; Rosàs, M; Sánchez-Palomino, S, 2015)
"Disulfiram was well tolerated at all doses."	2.80	Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. ( Bacchetti, P; Bumpus, N; Chang, CC; Deeks, SG; Elliott, JH; Gorelick, RJ; Hartogensis, W; Hoh, R; Lee, SA; Lewin, SR; Lifson, J; McMahon, JH; Piatak, M; Roney, J; Savic, R; Solomon, A, 2015)
"The combination of prolonged high-dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal."	1.72	Neurotoxicity with high-dose disulfiram and vorinostat used for HIV latency reversal. ( Blennow, K; Bumpus, N; Burger, D; Chang, J; Dantanarayana, A; Evans, VA; Fisher, K; Gisslen, M; Hagenauer, M; Heck, CJS; Howell, BJ; Lau, JSY; Lee, S; Lewin, SR; McMahon, JH; Palmer, S; Rasmussen, TA; Solomon, A; Symons, J; Tennakoon, S; Wu, G; Zerbato, JM; Zetterberg, HH; Zuck, P, 2022)
" We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation."	1.42	Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. ( Bullen, CK; Durand, CM; Hill, AL; Laird, GM; Martin, AR; Rosenbloom, DI; Siliciano, JD; Siliciano, RF, 2015)
"Disulfiram was safe and well tolerated."	1.40	A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. ( Andrade, A; Bacchetti, P; Buckheit, R; Bumpus, NN; Chander, G; Deeks, SG; Eisele, E; Emad, F; Hoh, R; Kennedy, M; Lai, J; McCance-Katz, EF; Siliciano, JD; Siliciano, RF; Spivak, AM, 2014)
"Disulfiram acts as an ACD blocker."	1.34	Are disulfiram-like reactions associated with abacavir-containing antiretroviral regimens in clinical practice? ( Barber, TJ; Mackie, NE; Marett, B; Portsmouth, S; Waldron, S; Weston, R; Winston, A, 2007)

Research

Studies (16)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Cell-associated HIV RNA

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	3 (18.75)	29.6817
2010's	12 (75.00)	24.3611
2020's	1 (6.25)	2.80

Authors	Studies
McMahon, JH	2
Evans, VA	1
Lau, JSY	1
Symons, J	1
Zerbato, JM	1
Chang, J	1
Solomon, A	2
Tennakoon, S	1
Dantanarayana, A	1
Hagenauer, M	1
Lee, S	1
Palmer, S	1
Fisher, K	1
Bumpus, N	2
Heck, CJS	1
Burger, D	1
Wu, G	1
Zuck, P	1
Howell, BJ	1
Zetterberg, HH	1
Blennow, K	1
Gisslen, M	1
Rasmussen, TA	2
Lewin, SR	3
Spivak, AM	2
Planelles, V	1
Kula, A	1
Delacourt, N	1
Bouchat, S	1
Darcis, G	1
Avettand-Fenoel, V	1
Verdikt, R	1
Corazza, F	1
Necsoi, C	1
Vanhulle, C	1
Bendoumou, M	1
Burny, A	1
De Wit, S	1
Rouzioux, C	1
Rohr, O	1
Van Lint, C	1
Tolstrup, M	1
Andrade, A	1
Eisele, E	1
Hoh, R	2
Bacchetti, P	2
Bumpus, NN	1
Emad, F	1
Buckheit, R	1
McCance-Katz, EF	1
Lai, J	1
Kennedy, M	1
Chander, G	1
Siliciano, RF	4
Siliciano, JD	4
Deeks, SG	2
Ramakrishnan, R	1
Liu, H	1
Rice, AP	1
Bullen, CK	3
Laird, GM	2
Durand, CM	2
Mothe, B	1
Climent, N	1
Plana, M	1
Rosàs, M	1
Jiménez, JL	1
Muñoz-Fernández, MÁ	1
Puertas, MC	1
Carrillo, J	1
Gonzalez, N	1
León, A	1
Pich, J	1
Arnaiz, JA	1
Gatell, JM	1
Clotet, B	1
Blanco, J	1
Alcamí, J	1
Martinez-Picado, J	1
Alvarez-Fernández, C	1
Sánchez-Palomino, S	1
Guardo, AC	1
Peña, J	1
Benito, JM	1
Rallón, N	1
Gómez, CE	1
Perdiguero, B	1
García-Arriaza, J	1
Esteban, M	1
López Bernaldo de Quirós, JC	1
Brander, C	1
García, F	1
Rosenbloom, DI	1
Martin, AR	1
Hill, AL	1
Elliott, JH	1
Chang, CC	1
Lee, SA	1
Hartogensis, W	1
Savic, R	1
Roney, J	1
Piatak, M	1
Gorelick, RJ	1
Lifson, J	1
Thirthalli, J	1
Chand, PK	1
Moling, O	1
Rimenti, G	1
Pristerà, R	1
Vedovelli, C	1
Pagani, L	1
Spoladore, G	1
Mian, P	1
Xing, S	1
Shroff, NS	1
Shan, L	1
Yang, HC	1
Manucci, JL	1
Bhat, S	1
Zhang, H	1
Margolick, JB	1
Quinn, TC	1
Margolis, DM	1
Doyon, G	1
Zerbato, J	1
Mellors, JW	1
Sluis-Cremer, N	1
Barber, TJ	1
Marett, B	1
Waldron, S	1
Portsmouth, S	1
Mackie, NE	1
Weston, R	1
Winston, A	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
IGHID 11424 - A Pilot Trial of the Effect of Vorinostat and AGS-004 on Persistent HIV-1 Infection (The VOR VAX Study)[NCT02707900]	Phase 1	6 participants (Actual)	Interventional	2016-03-31	Terminated (stopped due to Manufacturing of the AGS-004 HIV vaccine by Argos could no longer be provided.)
A Double-blind Phase I Study to Evaluate the Safety of the HIV-1 Vaccine MVA-B in Chronic HIV-1 Infected Patients Successfully Treated With HAART[NCT01571466]	Phase 1	30 participants (Actual)	Interventional	2011-09-30	Completed
Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study[NCT01944371]	Phase 1/Phase 2	30 participants (Actual)	Interventional	2013-09-30	Completed
DISulfiram for COvid-19 (DISCO) Trial: A Phase 2 Double-Blind, Randomized Placebo-Controlled Trial of Disulfiram Compared to Standard Care in Patients With Symptomatic COVID-19[NCT04485130]	Phase 2	11 participants (Actual)	Interventional	2021-08-18	Terminated (stopped due to Low COVID case numbers, competing COVID treatments available)
Simultaneous Disruption of Latency and Immune Enhancement by Poly-ICLC During HIV-1 Infection[NCT02071095]	Phase 1/Phase 2	15 participants (Actual)	Interventional	2014-04-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Fold change cell-associated HIV RNA in Total CD4 T-Cells. (NCT01944371)
Timeframe: Baseline and 3 days

Disufiram Pharmacokinetics

Intervention	Fold change (Mean)
Disulfiram 500mg	1.7
Disulfiram 1000mg	1.9
Disulfiram 2000mg	1.6

Plasma concentrations of disulfiram were measured on dosing day 1 (hours 0, 2, and 6), day 2 (hour 0), and day 3 (hours 0, 2, and 6), as well as on postdosing days 4, 8, and 31. The area under the curve (AUC) levels over 72 hours was estimated. (NCT01944371)
Timeframe: 31 days

Plasma HIV RNA

Intervention	mg-hour/liter (Mean)
Disulfiram 500mg	3,186
Disulfiram 1000mg	8,386
Disulfiram 2000mg	22,331

Fold change in plasma HIV RNA levels from baseline through day 3 (NCT01944371)
Timeframe: Baseline and 3 days

Proviral HIV DNA

Intervention	Fold change (Mean)
Disulfiram 500mg	1.50
Disulfiram 1000mg	0.90
Disulfiram 2000mg	1.22

Fold change in HIV DNA levels between Baseline and Day 30 (NCT01944371)
Timeframe: Baseline and 30 days

Change in COVID-19 Symptom Severity Score as Assessed by a 5-point Adapted Somatic Symptom Severity Score (SSS-8)

Intervention	Fold change (Mean)
Disulfiram 500mg	1.07
Disulfiram 1000mg	0.83
Disulfiram 2000mg	0.91

"The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant. A question about how much the symptoms bother the participants will be asked. The participant will rank 1 as not at all, 2 as a little bit, 3 as somewhat, 4 as quite a bit and 5 as very much. Higher values represent worse outcomes. Scales are combined to compute a total score at Day 0 and Day 31. A change of the median is reported." (NCT04485130)
Timeframe: Day 0 and Day 31

Virologic Impact of 5 Days of Disulfiram, as Measured by the Change in Copies of SARS-CoV-2 Virus Per mL Between Baseline and Day 31.

Intervention	units on a scale (Median)
Cohort 1: Disulfiram	-2.60
Cohort 1: Placebo	-2.14

Change in copies of SARS-CoV-2 PCR virus per mL between Baseline and Day 31. (NCT04485130)
Timeframe: Day 0 and Day 31

Immunologic Impact of 5 Days of Disulfiram, as Measured by the Fold-change in Plasma Levels of Pro-inflammatory Cytokines (e.g, Interleukin 6, Interleukin 1-beta, Etc.).

Intervention	copies/mL (Mean)
Cohort 1: Disulfiram 1000 mg	-20.89
Cohort 1: Placebo	-20

Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31. (NCT04485130)
Timeframe: Day 0 and Day 31

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Intervention	fold change (Median)
	Change in IL-6 (pg/mL) Day 0 to 31	Change in IL-1B (pg/mL) Day 0 to 31
Cohort 1: Disulfiram 100 mg	-0.1186	-0.1402
Cohort 1: Placebo	-0.0215	0.0268

The safety and tolerability of a 5 day course of disulfiram. The number of adverse events and their grade will be determined for each participant. (NCT04485130)
Timeframe: Day 0 and Day 31

CD8 CD38 (Mean of Fluorescence)

Intervention	Participants (Count of Participants)
	AE Grade 3 or Higher	AE Grade 1 or 2
Cohort 1: Disulfiram 1000 mg	0	4
Cohort 1: Placebo	1	1

the CD38-activation marker on CD8 T-cells (CD8/CD38). (NCT02071095)
Timeframe: Day 8

NK Cell Number

Intervention	mean fluorescent intensity (MFI) (Mean)
Arm A: Poly-ICLC	8.69
Arm B: Normal Saline	2.35

Natural killer cells or NK cells are part of the innate immune defense against infection and cancer. (NCT02071095)
Timeframe: at 48 weeks

Number Participants With Adverse Events

Intervention	cells/µL (Mean)
Arm A: Poly-ICLC	20.68
Arm B: Normal Saline	19.41

Safety measured by number of participants with adverse events. (NCT02071095)
Timeframe: Up to 48 weeks

Percent Change in CD4+ Tcell-associated HIV-1 RNA as Compared to Baseline

Intervention	Participants (Count of Participants)
Arm A: Poly-ICLC	11
Arm B: Normal Saline	3

CD4+ Tcell-associated HIV-1 RNA to determine whether Poly-ICLC disrupts viral latency in HIV-1-infected individuals on anti-retroviral therapy.Viral transcription assessed by monitoring cell associated HIV-1 RNA. Percent change compared to baseline. (NCT02071095)
Timeframe: Baseline, Day 2, Day 4, Day 8, Day 28

Plasma Interferon-gamma-inducible Protein-10 (IP-10) Level

Intervention	percent change (Mean)
	Day 2	Day 4	Day 8	Day 28
Arm A: Poly-ICLC	102.8	134.8	161.0	199.6
Arm B: Normal Saline	186.3	254.7	66.33	126.7

One of the biomarkers of cellular immune activation and exhaustion quantified by flow cytometry. Normal range is 7.8-500 pg/ml. (NCT02071095)
Timeframe: Day 2 and Day 4

Article	Year
Novel Latency Reversal Agents for HIV-1 Cure. Annual review of medicine, 2018, 01-29, Volume: 69 Topics: Acetaldehyde Dehydrogenase Inhibitors; Adjuvants, Immunologic; Disulfiram; Histone Deacetylase Inhib	2018
Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents? Current opinion in HIV and AIDS, 2016, Volume: 11, Issue:4 Topics: Anti-HIV Agents; Clinical Trials as Topic; Disulfiram; Histone Deacetylase Inhibitors; HIV Infection	2016
The implications of medication development in the treatment of substance use disorders in developing countries. Current opinion in psychiatry, 2009, Volume: 22, Issue:3 Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Buprenorphine; Comorbidity; Developing Countries; Disul	2009

Article	Year
Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. The Journal of antimicrobial chemotherapy, 2015, Volume: 70, Issue:6 Topics: Adult; AIDS Vaccines; Anti-HIV Agents; Disulfiram; Drug Carriers; Female; gag Gene Products, Human I	2015
Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. The lancet. HIV, 2015, Volume: 2, Issue:12 Topics: Adult; Anti-Retroviral Agents; Australia; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Disulfir	2015
Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. The lancet. HIV, 2015, Volume: 2, Issue:12 Topics: Adult; Anti-Retroviral Agents; Australia; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Disulfir	2015
Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. The lancet. HIV, 2015, Volume: 2, Issue:12 Topics: Adult; Anti-Retroviral Agents; Australia; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Disulfir	2015
Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. The lancet. HIV, 2015, Volume: 2, Issue:12 Topics: Adult; Anti-Retroviral Agents; Australia; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Disulfir	2015

Article	Year
Neurotoxicity with high-dose disulfiram and vorinostat used for HIV latency reversal. AIDS (London, England), 2022, 01-01, Volume: 36, Issue:1 Topics: Disulfiram; Drug Therapy, Combination; HIV Infections; Humans; Virus Latency; Vorinostat	2022
Heterogeneous HIV-1 Reactivation Patterns of Disulfiram and Combined Disulfiram+Romidepsin Treatments. Journal of acquired immune deficiency syndromes (1999), 2019, 04-15, Volume: 80, Issue:5 Topics: Anti-HIV Agents; Cell Line; Depsipeptides; Disulfiram; Drug Therapy, Combination; HIV Infections; HI	2019
Editorial commentary: Reversing latency in HIV-infected patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014, Volume: 58, Issue:6 Topics: Disulfiram; HIV Infections; HIV-1; Humans; Viremia; Virus Latency	2014
A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014, Volume: 58, Issue:6 Topics: Adult; Anti-Retroviral Agents; Disulfiram; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged;	2014
Short communication: SAHA (vorinostat) induces CDK9 Thr-186 (T-loop) phosphorylation in resting CD4+ T cells: implications for reactivation of latent HIV. AIDS research and human retroviruses, 2015, Volume: 31, Issue:1 Topics: Acetaldehyde Dehydrogenase Inhibitors; CD4-Positive T-Lymphocytes; Cell Line; Cyclin T; Cyclin-Depen	2015
New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nature medicine, 2014, Volume: 20, Issue:4 Topics: Anti-HIV Agents; Azepines; Bryostatins; CD4-Positive T-Lymphocytes; Cell Cycle Proteins; Depsipeptid	2014
Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. The Journal of clinical investigation, 2015, Volume: 125, Issue:5 Topics: Adult; Anti-HIV Agents; Azepines; Bryostatins; CD4-Positive T-Lymphocytes; Cells, Cultured; Disulfir	2015
Fatal lactic acidosis precipitated by nifedipine in a patient treated with disulfiram and antiretrovirals. Drug metabolism letters, 2009, Volume: 3, Issue:3 Topics: Acidosis, Lactic; Adult; Alcohol Deterrents; Alcoholism; Anti-Retroviral Agents; Antihypertensive Ag	2009
Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. Journal of virology, 2011, Volume: 85, Issue:12 Topics: Anti-HIV Agents; CD4-Positive T-Lymphocytes; Cells, Cultured; Disulfiram; Genes, bcl-2; HIV Infectio	2011
Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS (London, England), 2013, Jan-14, Volume: 27, Issue:2 Topics: CD4-Positive T-Lymphocytes; Cell Line; Disulfiram; Enzyme Inhibitors; Female; HIV Infections; HIV-1;	2013
Are disulfiram-like reactions associated with abacavir-containing antiretroviral regimens in clinical practice? AIDS (London, England), 2007, Aug-20, Volume: 21, Issue:13 Topics: Adult; Alcohol Drinking; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Dideoxynucleosides;	2007

disulfiram and HIV Coinfection