MedTrace Logo

The T Cell Activator of Cell Killing ("TACK") IT ON" STUDY

NCT06823596 · Status: RECRUITING · Phase: NA · Type: INTERVENTIONAL · Enrollment: 26

Last updated 2026-03-17

No results posted yet for this study

Summary

Antiretroviral therapy or ART blocks HIV replication reducing plasma viral loads to undetectable levels but has no effect on persistently infected cells in the body, called the virus reservoir. These cells carry infectious HIV capable of restarting HIV replication if therapy is stopped. The reservoir is so stable forcing people to adhere life-long ART. Over 5% of ART adherent individuals continue to have residual non-suppressive viremia (NSV) detected by clinical assays (40-400 copies/ml). Residual viremia reflects a more persistent reservoir and has the potential for increased morbidity. For eg., persistent expression of HIV proteins contributes to inflammation, and can lead to comorbidities. Recently, a novel way to target this reservoir called "TACK" or "Targeted activator of cell killing" is proposed. TACK compounds only target HIV infected cells and directly kill them by inducing a natural killing program (called the inflammasome). Recently the HIV drug, Efavirenz (EFV), which was used to suppress HIV replication for decades, has now been shown to also be a TACK compound. This pilot study will evaluate the impact of Efavirenz (EFV) in reducing HIV persistence by its ability to be a TACK molecule. So in addition to blocking HIV growth, this compound when added to a current ART regimen can kill HIV infected cells in the test tube. We aim to harness this effect to determine whether the addition of EFV to the current ART regimen in people with NSV can suppress the viremia to undetectable levels by killing those cells. NSV represents the "the tip of the iceberg" of those with bigger reservoirs and represents a challenging clinical scenario in dire need of new diagnostic and therapeutic options.

This pilot study will spark larger clinical trials to advance HIV cure strategies, and will provide new tools to improve the clinical management of people living with HIV.

Conditions

Interventions

DRUG

Efavirenz 600mg

Efavirenz induces pyroptosis of HIV expressing cells via the CARD8 inflammasome. In contrast to most ART drugs, and in addition to its anti-retroviral effect, EFV also induces intracellular Gag-Pol dimerization and premature HIV protease activation, causing cleavage of the inflammasome protein CARD8. CARD8 activation results in the production of effector molecules that rapidly kill virus-infected cells by pyroptosis. This effect of EFV has been called "TACK" or "T cell activator of cell killing". We aim to harness this effect to reduce residual nonsuppresible viremia (NSV) in people on stable antiretroviral therapy (ART). Participants in this study will receive EFV in addition to their stable ART regimen for two months, during and after which we will monitor plasma HIV RNA and markers of viral persistence and immune activation.

Sponsors & Collaborators

  • Ontario HIV Treatment Network

    collaborator NETWORK

  • Maple Leaf Research

    collaborator OTHER

  • Unity Health Toronto

    collaborator OTHER

  • University of Toronto

    lead OTHER

Principal Investigators

  • Mario Ostrowski, MD · University of Toronto

  • Colin Kovacs, MD · University of Toronto

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
89 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-01-14
Primary Completion
2027-11-15
Completion
2028-11-15

Countries

  • Canada

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06823596 on ClinicalTrials.gov