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

NCT04448158 | Completed

• 1 other identifier: ARVD-MUTARESERVOIR
• Study Type: observational
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

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

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

Interventions

Genotypic Resistance Test DIAGNOSTIC_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; 5 years of virological suppression

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• No genotypic resistance test available at time of failure.

Sponsors & Collaborators

• Association de Recherche en Virologie et Dermatologie: lead
• ViiV Healthcare: collaborator

Study Sites (1)

ARVD

Paris, France

Location

Study Officials

• Anne-Geneviève MARCELIN

  Sorbonne University; APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 25, 2020
• Study Start: July 1, 2020
• Primary Completion: May 1, 2021
• Study Completion: July 1, 2021
• Last Updated: February 10, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)