NCT03198559

Combination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART

Combination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART (DIVA): A Single Arm Clinical Trial

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: University of Melbourne · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Antiretroviral therapy (ART) dramatically reduces Human Immunodeficiency Virus (HIV) replication leading to restoration of immune function and a near normal life expectancy, but treatment is lifelong and there is no cure. The major barrier to a cure is the persistence of long lived cluster of differentiation 4 (CD4+) T-cells that contain a "silenced" form of HIV, called HIV latency. The purpose of this research is to investigate whether it may be possible to reduce the amount of dormant HIV infection in immune cells, by "turning on" or activating the virus and hence force it out of the latently infected memory T cells. This leads to production of HIV by the cell, which will either die or will be recognized and eliminated by the immune system. As very few T cells are latently infected with HIV, the death of these cells is not expected to affect the function of the immune system and further infection of new cells is expected to be prevented by ART.

Detailed description

One strategy aimed at reducing the frequency of latently infected cells in HIV-infected individuals on antiretroviral therapy (ART) is the use of pharmacological agents to reverse HIV latency, thereby initiating virus-mediated cell lysis or immune-mediated killing. Recent clinical trials of latency reversing agents (LRAs) in HIV infected subjects on ART, including histone deacetylase inhibitors (HDACi) and the anti-alcoholism drug disulfiram, have shown that inducing an increase in Cell Associated Unspliced (CA-US) HIV RNA or plasma HIV RNA is possible. Yet, these interventions did not have a demonstrable effect on the frequency of latently infected cells or time to viral rebound after cessation of ART, potentially because latency reversal alone didn't trigger an adequate immune response or cell death or that the potency of latency reversal with a single-agent intervention over a very short period of time, lacked sufficient potency, as suggested by recent in vitro studies. It is highly likely that long-term remission off ART will require interventions that lead to both a reduction in latently infected cells and an increase in HIV-specific immunity, therefore identifying a strategy to increase viral antigens on the surface of latently infected cells will be a key component of this strategy.

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	Disulfiram, (National Drug Code) NDC 0378-4141-01	This study will provide open label disulfiram. Participants will take 2 grams (4x500mg tablets) of disulfiram per day for a total of 28 days
DRUG	Vorinostat, NDC 00006-0568-40	This study will provide open label vorinostat. Participants will take 400mg (4x100mg capsules) of vorinostat per day on days 8, 9, 10 and days 22, 23, 24.

Timeline

• Start date: 2017-08-08
• Primary completion: 2019-04-09
• Completion: 2019-04-09
• First posted: 2017-06-26
• Last updated: 2024-02-09
• Results posted: 2024-02-09

Locations

1 site across 1 country: Australia