Clinical trial NCT01286259: Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals
Official title: Short-term Disulfiram Administration to Accelerate the Decay of the HIV Reservoir in Antiretroviral-treated HIV Infected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1 Infection
Keywords: HIV
HAART suppressed
Disulfiram
Antabuse
Latent reservoir
Eradication
Cure
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2011-01-31
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Documented continuous HAART for at least 18 months prior to study entry and on a stable regimen for at least 3 months prior to entry.
* Documented undetectable HIV viral loads for at least one year. Intermittent isolated episodes of detectable low-level viremia "blips" (\> 50 but \< 500 copies RNA/mL) remain eligible.
* Screening plasma HIV-1 RNA levels \< 40 copies RNA/mL.
* CD4 T-cell count above 200 cells/uL for 24 weeks prior to screen.
* \>90% adherence to therapy within the preceding 30 days.
* Females 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.
* Willing to abstain from any alcohol during the two week period in which disulfiram will be administered and during the two week period immediately after disulfiram administration.

Exclusion Criteria:

* Current alcohol use disorder or hazardous alcohol use as determined by clinical evaluation.
* Current use of any drug formulation that contains alcohol or that might contain alcohol.
* Current use of tipranavir.
* Current use of maraviroc.
* Current use of warfarin.
* Intending to modify antiretroviral therapy in the next 27 weeks for any reason.
* Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
* Severe myocardial disease or coronary artery disease.
* History of psychosis.
* Clinically active hepatitis determined by the study physician; ALT or AST \>3 x the upper limit of normal.
* Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks.
* Pregnant or breastfeeding women.

Primary outcomes:
measure: 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
timeFrame: 12 weeks
measure: Number of Participants With Adverse Events
timeFrame: Two weeks
measure: The Fold Change in Mean Levels of Viremia During and After Disulfiram Dosing as Compared to Baseline Levels
timeFrame: Baseline to Day 18
measure: Number of Participants With Detectable Plasma HIV RNA
timeFrame: Two weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: University of California, San Francisco
name: Steven G. Deeks, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Adriana Andrade, M.D.
role: PRINCIPAL_INVESTIGATOR
References: