Effect of Dolutegravir Intensification on HIV-1 Reservoirs

HIV-1-infection Clinical Trial

— EDIT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05351684
• Other study ID #: 2018-228
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2019
• Est. completion date: December 13, 2022

Study information

• Verified date: December 2022
• Source: University of Liege
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 13, 2022
• Est. primary completion date: August 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Dolutegravir 50 MG
already included in arm/group descriptions.

Locations

Country	Name	City	State
Belgium	Liège university hospital	Liège

Sponsors (1)

Lead Sponsor	Collaborator
University of Liege

Country where clinical trial is conducted

Belgium, 

Outcome

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