Effect of Dolutegravir Intensification on HIV-1 Reservoirs (EDIT)

Effect of Dolutegravir Intensification on Blood and Tissue Latent HIV-1 Reservoirs and on Residual Viremia Despite ART

Persistent HIV viremia occurs in most ART-treated patients and could arise from reactivation of viral expression from latently-infected cells that constitute the viral latent reservoir (LR) and/or residual ongoing viral replication during cART, for instance in anatomical compartment where drug penetration is sub-optimal.

The question of the sources of persistent viremia is of the utmost importance. If ongoing viral replication occurs, it could induce deleterious consequences on reservoirs size and immune activation.We propose to better characterize the role ongoing viral replication to HIV persistence under ART by undertaking a treatment intensification trial with high-dose dolutegravir. Tissue/blood samples and replication-competent reservoir measurements will be included as outcomes as well as immune activation markers.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Dolutegravir 50 MG

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • Liege University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-infected adults receiving cART for at least 3 years
• Undetectable viral for at least 3 years
• DTG/3TC/ABC as cART regimen in the previous 6 months.
• CD4 counts higher than 200 cells per μL

Exclusion Criteria:

• active hepatitis C or B
• unstable liver disease
• renal impairment (estimated glomerular filtration rate <50 mL per min),
• gastrointestinal disorders that would affect the absorption of study treatment
• current use of drugs with significant interactions with dolutegravir
• current use of drugs with an impact on inflammation such as steroids.
• hospitalization for acute illness within the previous 8 weeks
• Pregnancy or breastfeeding.
• Anal or rectal lesions impeding rectal biopsies
• Decreased platelets count or coagulation disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensified; Group of patients whose treatment will be intensified with an additional 50mg of dolutegravir on top of regular treatment (Triumeq: ABC/3TC/DTG).	Drug: Dolutegravir 50 MG; already included in arm/group descriptions.
No Intervention: Control; Group of patients without modification of baseline treatment (Triumeq: ABC/3TC/DTG).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the impact of treatment intensification at the level of total and replication-competent reservoir (RCR) in blood and in tissues.	Measurements of blood and tissue HIV reservoir	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the impact of DTG treatment intensification on residual viremia	Measurement of HIV viremia at the single copy level	3 months
To evaluate the impact of DTG treatment intensification on immune activation	Measurement of T cell activation markers	3 months
To investigate the correlation between blood and tissues HIV reservoir	Measurement of blood and tissue HIV reservoir	3 months
To correlate the concentration of DTG with residual viremia and impact on HIV reservoir	Measurement of DTG blood concentration	3 months
To evaluate the impact of DTG treatment intensification on inflammation	Measurement on inflammatory markers in blood	3 months

Collaborators and Investigators

• Sponsor: University of Liege

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): August 28, 2022
• Study Completion (Actual): December 13, 2022

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Estimate): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir
• Other Study ID Numbers: 2018-228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No