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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

Tracking Information
First Submitted Date June 23, 2020
First Posted Date June 25, 2020
Last Update Posted Date September 25, 2020
Actual Study Start Date July 1, 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 23, 2020)
  • 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.
  • Percentage of M184V mutation [ Time Frame: One measure per year ]
    Percentage detected by UltraDeep Sequencing
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy
Official Title Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy
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 Provided
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.
Condition 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.
Study Groups/Cohorts
  • 5 years of virological suppression
    - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years
    Intervention: 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
    Intervention: Diagnostic Test: Genotypic Resistance Test
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 23, 2020)
200
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Anne-Geneviève MARCELIN 0033142177401 anne-genevieve.marcelin@aphp.fr
Contact: Eve TODESCO 0033142177401 eve.todesco@aphp.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT04448158
Other Study ID Numbers ARVD-MUTARESERVOIR
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Association de Recherche en Virologie et Dermatologie
Study Sponsor Association de Recherche en Virologie et Dermatologie
Collaborators ViiV Healthcare
Investigators
Principal Investigator: Anne-Geneviève MARCELIN Sorbonne University; APHP
PRS Account Association de Recherche en Virologie et Dermatologie
Verification Date September 2020