<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04448158</url>
  </required_header>
  <id_info>
    <org_study_id>ARVD-MUTARESERVOIR</org_study_id>
    <nct_id>NCT04448158</nct_id>
  </id_info>
  <brief_title>Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy</brief_title>
  <acronym>MUTARESERVOIR</acronym>
  <official_title>Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Association de Recherche en Virologie et Dermatologie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ViiV Healthcare</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Association de Recherche en Virologie et Dermatologie</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In view of the prolongation of patients living with HIV's life expectancy, the question of&#xD;
      optimization of ART, which is still a life-long treatment, becomes central. While most&#xD;
      patients achieve virological success, their treatments often need to be optimized in order to&#xD;
      limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen&#xD;
      strategies represent one of the approaches for treatment optimization.&#xD;
&#xD;
      Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can&#xD;
      persist for an unknown duration and reemerge in case of therapeutic selective pressure.&#xD;
&#xD;
      There is a need to assess the dynamic of archived Drug resistance associated mutations&#xD;
      (DRAMs) clearance in cell-associated HIV DNA after a long period of virological control, in&#xD;
      the perspective of ARVs recycling.&#xD;
&#xD;
      The investigators postulate that it could be interesting in the future to recycle ARV drugs&#xD;
      (that where classified as &quot;resistant&quot; in the past) in subsequent regimen. The question is&#xD;
      particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen&#xD;
      (disappearance of M184V).&#xD;
&#xD;
      Thus, the investigators propose a retrospective, longitudinal analysis on&#xD;
      blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep&#xD;
      Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug&#xD;
      resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained&#xD;
      virological control for at least 5 years under effective ART.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">July 1, 2021</completion_date>
  <primary_completion_date type="Actual">May 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of M184V mutation</measure>
    <time_frame>One measure per year</time_frame>
    <description>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 &gt; 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 &gt; 1% in a sample and a percentage &lt; 1% in the subsequent sample.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of M184V mutation</measure>
    <time_frame>One measure per year</time_frame>
    <description>Percentage detected by UltraDeep Sequencing</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">79</enrollment>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>5 years of virological suppression</arm_group_label>
    <description>- Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10 years of virological suppression</arm_group_label>
    <description>- Patients harboring a fully suppressed HIV-1 plasma viral load for at least 10 years</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Genotypic Resistance Test</intervention_name>
    <description>A Genotypic Resistance Test by Sanger sequencing will be done after the period of virological suppression.&#xD;
If M184V is still present no additional test will be performed.&#xD;
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.</description>
    <arm_group_label>10 years of virological suppression</arm_group_label>
    <arm_group_label>5 years of virological suppression</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The studied population will be composed of followed HIV infected patients of the center, of&#xD;
        whom approximately 90% are under treatment and virologically suppressed, consecutively&#xD;
        selected (in an anti-chronological order on the sample failure date) until gathering the&#xD;
        requested number of patients meeting the eligibility criteria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infected&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Genotypic resistance test performed at time of failure and harboring at least M184V&#xD;
&#xD;
          -  Fully suppressed HIV viral load for at least 5 or 10 years.&#xD;
&#xD;
          -  Triple therapy or 2 drug regimen during the entire follow-up&#xD;
&#xD;
          -  Availability of at least 1 stored whole blood sample /year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No genotypic resistance test available at time of failure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne-Geneviève MARCELIN</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sorbonne University; APHP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ARVD</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04448158
org study id: ARVD-MUTARESERVOIR
nct id: NCT04448158
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Case-Only
time perspective: Retrospective
measure: Detection of M184V mutation
time frame: One measure per year
description: 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.
measure: Percentage of M184V mutation
time frame: One measure per year
description: Percentage detected by UltraDeep Sequencing
arm group label: 5 years of virological suppression
description: - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years
arm group label: 10 years of virological suppression
description: - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 10 years
intervention type: Diagnostic Test
intervention name: Genotypic Resistance Test
description: 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.
arm group label: 10 years of virological suppression
arm group label: 5 years of virological suppression
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anne-Geneviève MARCELIN
role: Principal Investigator
affiliation: Sorbonne University; APHP
facility: 
country: France
responsible party type: Sponsor
sharing ipd: No