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

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ClinicalTrials.gov Identifier: NCT04448158
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : September 25, 2020
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment
HIV-1-infection Diagnostic Test: Genotypic Resistance Test

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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.




Primary Outcome Measures :
  1. Detection of M184V mutation [ Time Frame: 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.

  2. Percentage of M184V mutation [ Time Frame: One measure per year ]
    Percentage detected by UltraDeep Sequencing



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04448158


Contacts
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Contact: Anne-Geneviève MARCELIN 0033142177401 anne-genevieve.marcelin@aphp.fr
Contact: Eve TODESCO 0033142177401 eve.todesco@aphp.fr

Locations
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France
ARVD Recruiting
Paris, France
Contact: Anne-Geneviève MARCELIN    0033142177514    anne-genevieve.marcelin@aphp.fr   
Sponsors and Collaborators
Association de Recherche en Virologie et Dermatologie
ViiV Healthcare
Investigators
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Principal Investigator: Anne-Geneviève MARCELIN Sorbonne University; APHP
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Responsible Party: Association de Recherche en Virologie et Dermatologie
ClinicalTrials.gov Identifier: NCT04448158    
Other Study ID Numbers: ARVD-MUTARESERVOIR
First Posted: June 25, 2020    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No