Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy (MUTARESERVOIR)

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.

Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for an unknown duration and reemerge in case of therapeutic selective pressure.

There is a need to assess the dynamic of archived Drug resistance associated mutations (DRAMs) clearance in cell-associated HIV DNA after a long period of virological control, in the perspective of ARVs recycling.

The investigators postulate that it could be interesting in the future to recycle ARV drugs (that where classified as "resistant" in the past) in subsequent regimen. The question is particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen (disappearance of M184V).

Thus, the investigators propose a retrospective, longitudinal analysis on blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained virological control for at least 5 years under effective ART.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Diagnostic test: Genotypic Resistance Test

• Study Type: Observational
• Enrollment (Actual): 79

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: Probability Sample

Study Population

The studied population will be composed of followed HIV infected patients of the center, of whom approximately 90% are under treatment and virologically suppressed, consecutively selected (in an anti-chronological order on the sample failure date) until gathering the requested number of patients meeting the eligibility criteria.

Description

Inclusion Criteria:

• HIV-1 infected
• Age ≥ 18 years
• Genotypic resistance test performed at time of failure and harboring at least M184V
• Fully suppressed HIV viral load for at least 5 or 10 years.
• Triple therapy or 2 drug regimen during the entire follow-up
• Availability of at least 1 stored whole blood sample /year

Exclusion Criteria:

• No genotypic resistance test available at time of failure.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
5 years of virological suppression; - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years	Diagnostic test: Genotypic Resistance Test; A Genotypic Resistance Test by Sanger sequencing will be done after the period of virological suppression.; If M184V is still present no additional test will be performed.; If M184V is absent, we will go back in the previous samples (one per year) to determine the time point where the mutation has been cleared by sanger and UDS sequencing.
10 years of virological suppression; - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 10 years	Diagnostic test: Genotypic Resistance Test; A Genotypic Resistance Test by Sanger sequencing will be done after the period of virological suppression.; If M184V is still present no additional test will be performed.; If M184V is absent, we will go back in the previous samples (one per year) to determine the time point where the mutation has been cleared by sanger and UDS sequencing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of M184V mutation	The persistence of M184V resistance mutation is defined by the detection of this mutation in 2 consecutive samples by Sanger and by a percentage of this mutation > 1% in 2 consecutive samples by UltraDeep Sequencing. The clearance of M184V is defined by the detection of this mutation by Sanger in a sample and the absence in the subsequent sample or a percentage of this mutation > 1% in a sample and a percentage < 1% in the subsequent sample.	One measure per year
Percentage of M184V mutation	Percentage detected by UltraDeep Sequencing	One measure per year

Collaborators and Investigators

• Sponsor: Association de Recherche en Virologie et Dermatologie
• Collaborators: ViiV Healthcare
• Investigators: Principal Investigator: Anne-Geneviève MARCELIN, Sorbonne University; APHP

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2020
• Primary Completion (ACTUAL): May 1, 2021
• Study Completion (ACTUAL): July 1, 2021

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (ACTUAL): June 25, 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-MUTARESERVOIR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No