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

HIV-1-infection Clinical Trial

— MUTARESERVOIR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04448158
• Other study ID #: ARVD-MUTARESERVOIR
• Status: Completed
• Start date: July 1, 2020
• Est. completion date: July 1, 2021

Study information

• Verified date: February 2023
• Source: Association de Recherche en Virologie et Dermatologie
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: July 1, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

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.

Locations

Country	Name	City	State
France	ARVD	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Association de Recherche en Virologie et Dermatologie	ViiV Healthcare

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of M184V mutation	Percentage detected by UltraDeep Sequencing	One measure per year