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

Completed

• Conditions: HIV-1-infection
• Interventions: Diagnostic Test: Genotypic Resistance Test

• Registration Number: NCT04448158
• Lead Sponsor: Association de Recherche en Virologie et Dermatologie

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-23
• Study First Submitted QC: 2020-06-23
• Study First Posted: 2020-06-25
• Study Start: 2020-07-01
• Primary Completion: 2021-05-01
• Study Completion: 2021-07-01
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-09
• Last Update Posted: 2023-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
5 years of virological suppression	Genotypic Resistance Test	- Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years
10 years of virological suppression	Genotypic Resistance Test	- Patients harboring a fully suppressed HIV-1 plasma viral load for at least 10 years

Primary Outcome Measures

Name	Time	Method
Detection of M184V mutation	One measure per year	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.
Percentage of M184V mutation	One measure per year	Percentage detected by UltraDeep Sequencing

Trial Locations

Locations (1)

ARVD; 🇫🇷 Paris, France