Ignite Creation Date:
2024-05-06 @ 10:12 AM
Last Modification Date:
2024-10-26 @ 12:26 PM
Study NCT ID:
NCT03198559
Status:
TERMINATED
Last Update Posted:
2024-02-09
First Post:
2017-06-14
Brief Title:
Combination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART
Sponsor:
University of Melbourne
Organization:
University of Melbourne
Study Overview
Official Title:
Combination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART DIVA A Single Arm Clinical Trial
Status:
TERMINATED
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
A re-evaluation of research risks to participants were greater than originally anticipated
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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 didnt 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None