Impact of DOlutegravir+Lamivudine Simplification on HIV-1 Reservoirs (IDOLTIB)

Impact of DOlutegravir+Lamivudine Simplification on TIssue and Blood Latent Replication-competent HIV-1 Reservoirs (IDOLTIB Study)

For a few years, there has been a keen interest of clinicians and patients for "lighter" antiretroviral strategies based on two- or even single drug regimens rather than the canonical triple therapy, both as initial and maintenance therapy, despite the possibility that ongoing viral replication may occur in some patients under triple-therapy.

We will therefore propose such simplification strategy (DTG/3TC) while maintaining triple-therapy (DTG/ABC/3TC) in a control group and will perform an in depth analysis of the replication-competent reservoir in blood and in tissues as well as measurements of residual viremia and immune chronic activation/inflammation.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Treatment simplification (dolutegravir lamivudine)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 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 2 years
• DTG/3TC/ABC as cART regimen in the previous 6 months.
• CD4 counts higher than 200 cells per μL and virological suppression for at least 2 years (plasma HIV RNA <20 copies per mL)

Exclusion Criteria:

• hepatitis C or B co-infection
• 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.
• Known resistance to DTG or 3TC
• Active tuberculosis
• 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: 2DR; Switch from 3 drug regimen (DTG+ABC+3TC) to 2 drug regimen (DTG+3TC)	Drug: Treatment simplification (dolutegravir lamivudine); Switch from 3 drug regimen (DTG/ABC/3TC) to 2 drug regimen
No Intervention: 3DR; Continued 3 drug regimen treatment (DTG+ABC+3TC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The impact of dual-therapy Dolutegravir (DTG) + Lamivudine (3TC) at the level of replication-competent reservoir (RCR) in blood and in tissues.	Measurements of RCR in the blood and tissues (rectal biopsies)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The impact of dual-therapy Dolutegravir (DTG) + Lamivudine (3TC) on residual viremia.	1 year
The impact of dual-therapy Dolutegravir (DTG) + Lamivudine (3TC) at the level of chronic immune activation/inflammation.	1 year
The correlation between blood and tissues RCR in a high number of patients under suppressive antiretroviral therapy.	1 year
The level of clonal expansion in the blood and tissue RCR	1 year
The correlation between the size of the blood/tissues RCR and the level of chronic immune activation/inflammation.	1 year

Collaborators and Investigators

• Sponsor: University of Liege
• Investigators: Principal Investigator: Gilles Darcis, MD PhD, Liege University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Lamivudine; Dolutegravir
• Other Study ID Numbers: 13011987

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol

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