Effect of Dolutegravir Intensification on HIV-1 Reservoirs

Phase 2

Completed

• Conditions: HIV-1-infection
• Interventions: Drug: Dolutegravir 50 MG

• Registration Number: NCT05351684
• Lead Sponsor: University of Liege

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-01
• Study First Submitted: 2019-10-24
• Study First Submitted QC: 2022-04-27
• Study First Posted: 2022-04-28
• Primary Completion: 2022-08-28
• Status Verified: 2022-12
• Study Completion: 2022-12-13
• Last Update Submitted: 2022-12-14
• Last Update Posted: 2022-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensified	Dolutegravir 50 MG	Group of patients whose treatment will be intensified with an additional 50mg of dolutegravir on top of regular treatment (Triumeq: ABC/3TC/DTG).

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Liège university hospital; 🇧🇪 Liège, Belgium