Effect of Dolutegravir Intensification on HIV-1 Reservoirs

Study Overview
=================
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.

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

Conditions
-----------------
HIV-1-infection

Intervention / Treatment
-----------------
* Drug: Dolutegravir 50 MG


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensified<br>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<br>* already included in arm/group descriptions.<br>|
| No Intervention: Control<br>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 |