Impact of M184V on the Virological Efficacy to 3TC/DTG (LAMRES) (LAMRES)

Impact of M184V on the Virological Efficacy to Lamivudine/Dolutegravir

In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization. Indeed, dual therapy regimens have shown non-inferior efficacy vs triple therapy as simplification therapy and more recently also as first line therapy. From the real-life data it emerges that today in simplification strategies, the dual regimen therapies are prescribed even in patients with a history of virological failure. Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for years and can reemerge in case of therapeutic selective pressure. In particular, previous selection of M184V may have an impact on virological response to 3TC/DTG. There are few data on a direct comparison of 3TC/DTG efficacy in patients harboring or not harboring the M184V. So, there is a need to assess the efficacy of 3TC/DTG in patients with past M184V mutation in a large set of patients followed in clinical setting.

Thus, the investigators propose a retrospective study of patients with HIV-RNA ≤50 copies/mL who were switched to 3TC/DTG in order to compare the virological efficacy of 3TC/DTG in patients with and without a history of M184V detection in a previous resistance genotype. This study aimed to analyze 800 patients switched to DTG/3TC in clinical real setting in large European (France, Italy, Spain) database.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection

• Study Type: Observational
• Enrollment (Actual): 712

Contacts and Locations

Study Locations

• France
  • Paris, France
    • ARVD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-1-infected patients with (i) age ≥18 years, (ii) HIV-RNA ≤50 copies/mL on any ART regimen, (iii) subsequently switching to DTG/3TC, (iv) with at least 1 previous plasma HIV-1 RNA or HIV-DNA genotype, (v) with at least 1 virological and clinical follow-up after switching to DTG/3TC.

The occurrence of M184V will be assessed using historical genotypic resistance tests; that is, any detection of this mutation in any previous resistance test will be scored as positive.

Description

Inclusion Criteria:

• HIV-1 infected
• Age ≥ 18 years
• Switched to 3TC/DTG while having HIV-RNA ≤50 copies/mL on any ART regimen
• Followed for at least 1 year after 3TC/DTG switch
• With at least 1 previous genotype
• With at least 1 virological follow-up after switching to 3TC/DTG

Exclusion Criteria:

• No genotypic resistance test available before switching to DTG/3TC

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
M184V + group and M184 - group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
probability of virological failure	probability of virological failure that is defined as HIV-RNA >50 copies/mL in 2 consecutive determinations or ≥200 copies/mL in a single determination. This outcome will be evaluated overall and between the M184V- and M184V+ patients' groups.	12 months

Collaborators and Investigators

• Sponsor: Association de Recherche en Virologie et Dermatologie

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2020
• Primary Completion (ACTUAL): June 1, 2022
• Study Completion (ACTUAL): August 1, 2022

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (ACTUAL): September 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ARVD-LAMRES

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