HIV-1-infection
Conditions
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.
Interventions
already included in arm/group descriptions.
Sponsors
University of Liege
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the impact of DTG treatment intensification on residual viremia | 3 months | Measurement of HIV viremia at the single copy level |
| To evaluate the impact of DTG treatment intensification on immune activation | 3 months | Measurement of T cell activation markers |
| To investigate the correlation between blood and tissues HIV reservoir | 3 months | Measurement of blood and tissue HIV reservoir |
| To correlate the concentration of DTG with residual viremia and impact on HIV reservoir | 3 months | Measurement of DTG blood concentration |
| To evaluate the impact of DTG treatment intensification on inflammation | 3 months | Measurement on inflammatory markers in blood |
Countries
Belgium
Outcome results
None listed