<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/NCT02247687</url>
  </required_header>
  <id_info>
    <org_study_id>ANRS 161 L-Vir</org_study_id>
    <secondary_id>2014-001663-13</secondary_id>
    <nct_id>NCT02247687</nct_id>
  </id_info>
  <brief_title>Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)</brief_title>
  <official_title>Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ANRS, Emerging Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen-Cilag Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>ANRS, Emerging Infectious Diseases</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Management of participants with low-level persistent viremia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ANRS 161 L-Vir is a phase III prospective, randomized, multicenter, open-label, superiority&#xD;
      trial for participants with low-level persistent viremia.&#xD;
&#xD;
      Participants will be randomized with a 1:1:1 ratio to the following three arms,&#xD;
&#xD;
        -  Reference arm : counseling without antiretroviral treatment modification&#xD;
&#xD;
        -  Switch arm : switch of current PI/r for Prezista® (darunavir)/ Norvir® (ritonavir)&#xD;
           (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with&#xD;
           counseling.&#xD;
&#xD;
        -  Addition of Isentress® (raltégravir) arm : Isentress® (raltegravir) 400 mg two times a&#xD;
           day (BID) added to current antiretroviral treatment with counseling&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low recruitment of participants for the study&#xD;
  </why_stopped>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients in Virologic success by week 12</measure>
    <time_frame>week 12</time_frame>
    <description>A virologic success is defined by a patient having plasma HIV-1 RNA levels &lt;50 copies/ml at weeks 8 and 12.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with HIV-1 RNA &lt; 50 copies/ml</measure>
    <time_frame>week 4, week 8, week 12, week 24, week 36, week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with HIV-1 RNA &lt; 20 copies/ml</measure>
    <time_frame>week 4, week 8, week 12, week 24, week 36, week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with HIV-1 RNA &lt;1copy/ml</measure>
    <time_frame>week 8, week 12, week 24, week 36, week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CD4 cells count from baseline</measure>
    <time_frame>week 12, week 24, week 48 and end visit</time_frame>
    <description>•Change was calculated as the CD4 count at the corresponding week minus the baseline CD4 count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Virologic Failure and Emergence of Resistance</measure>
    <time_frame>day 0 and visit at failure time</time_frame>
    <description>•resistance patterns at failure time compared with day 0, in HIV-DNA and in HIV-RNA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of HIV DNA in peripheral blood mononucleated cell (PBMC)</measure>
    <time_frame>day 0</time_frame>
    <description>Quantification of HIV DNA in PBMC at day 0 and its association with the proportion of success in each arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of antiretroviral drugs in plasma</measure>
    <time_frame>day 0 and end visit</time_frame>
    <description>•plasma concentrations of antiretroviral drugs and correlation with success or failure of the strategy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of antiretroviral drugs in hair</measure>
    <time_frame>day 0, week 12, week 24and end visit</time_frame>
    <description>•measurement of concentrations of antiretroviral drugs treatments in hair</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of HIV-1 RNA in seminal plasma</measure>
    <time_frame>day 0, week 12, week 48 and end visit</time_frame>
    <description>quantification of HIV RNA in seminal plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Study interruption</measure>
    <time_frame>From day 0 to week 24</time_frame>
    <description>•proportion of participants who discontinued the strategy assigned by randomization at day 0 because of failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of clinical and biological adverse events</measure>
    <time_frame>from day 0 to week 48</time_frame>
    <description>• proportions of participants experiencing a clinical or biological adverse events (ANRS scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported adherence</measure>
    <time_frame>day 0, week 4, week 8, week 12, week 24, week 36, week 48 and end visit</time_frame>
    <description>•self-reported percentage of antiretroviral treatment participant had taken during the last 4 weeks</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>HIV-1 Infection</condition>
  <condition>Treatment Resistant Disorders</condition>
  <condition>Viremia</condition>
  <arm_group>
    <arm_group_label>Counseling arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Counseling without antiretroviral treatment modification</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Switch arm for protease inhibitor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Switch arm for protease inhibitor : intervention is the switch of current boosted protease inhibitor for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Addition of Isentress® (raltegravir)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Addition of Isentress® (raltegravir) arm&#xD;
• Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Protease inhibitor</intervention_name>
    <description>Modification in the antiretroviral treatment&#xD;
•Switch arm for protease inhibitor : intervention switch of current boosted protease inhibitor for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.</description>
    <arm_group_label>Switch arm for protease inhibitor</arm_group_label>
    <other_name>Prezista® / Norvir®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isentress® (raltegravir)</intervention_name>
    <description>• Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling</description>
    <arm_group_label>Addition of Isentress® (raltegravir)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Counseling arm</intervention_name>
    <description>No change of antiretroviral treatment but only counseling</description>
    <arm_group_label>Counseling arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  HIV-1 infection&#xD;
&#xD;
          -  On combined antiretroviral regimen for at least 18 months&#xD;
&#xD;
          -  Participant with a stable antiretroviral regimen for at least 6 months, including 2&#xD;
             Reverse-transcriptase inhibitor (INTI) + 1 Boosted Protease Inhibitor IP/r ,&#xD;
&#xD;
          -  participant with at least 2 consecutive viral load between 50 and 500&#xD;
             copies/milliliter over the last 9 months (with at least 2 months between the two&#xD;
             measurements) quantified with the same commercial kit.&#xD;
&#xD;
          -  50 &lt;or= VL &lt; 500 copies/milliliter at screening visit quantified with the same&#xD;
             commercial kit than previous one.&#xD;
&#xD;
          -  Participant naïve to raltegravir (RAL)&#xD;
&#xD;
          -  failure of amplification or successful realization of genotypic resistance test&#xD;
             without evidence for resistance mutations against current treatment (3TC/FTC accepted&#xD;
             with M184V mutation)&#xD;
&#xD;
          -  creatinin &lt; 3 Upper Limit normal (ULN)&#xD;
&#xD;
          -  Aspartate Amino Transférase (ASAT), Alanine Amino Transférase (ALAT) &lt; 5 Upper Limit&#xD;
             normal (ULN)&#xD;
&#xD;
          -  hemoglobin &gt; 8 g/dL&#xD;
&#xD;
          -  platelets &gt; 50 000/mm3&#xD;
&#xD;
          -  In women, lack of current pregnancy verified by Beta Human Chorionic Gonadotropin&#xD;
             (βHCG) at week -4 visit and use of a mechanical contraceptive method&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Participants with an active health insurance coverage (article L1121-11 du Code de la&#xD;
             Santé Publique)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV-2 infection,&#xD;
&#xD;
          -  severe medical condition in the last month (inclusion is possible for a stable&#xD;
             condition at screening)&#xD;
&#xD;
          -  breastfeeding women, current pregnancy or planned pregnancy within 12 months.&#xD;
&#xD;
          -  participant currently receiving Prezista® (darunavir)/ Norvir® (ritonavir) (600/100&#xD;
             mg) two times a day (BID) (of note, participants receiving Prezista® (darunavir)/&#xD;
             Norvir® (ritonavir) one time a day (QD) can be included)&#xD;
&#xD;
          -  Hypersensitivity Prezista® (darunavir)/ Norvir® (ritonavir) or to any of the&#xD;
             excipients of the study treatment&#xD;
&#xD;
          -  participant under judicial protection (judicial protection due to temporarily and&#xD;
             slightly diminished mental or physical faculties), or under legal guardianship&#xD;
&#xD;
          -  planned absence that could prevent the patient from participating in the trial (travel&#xD;
             abroad, moving, pending work transfer ...)&#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>Jade Ghosn, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>APHP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Avicenne</name>
      <address>
        <city>Bobigny</city>
        <zip>93000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Jean Verdier</name>
      <address>
        <city>Bondy</city>
        <zip>93143</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint André</name>
      <address>
        <city>Bordeaux</city>
        <zip>33075</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pellegrin</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de la côte de Nacre</name>
      <address>
        <city>Caen</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Henry Mondor</name>
      <address>
        <city>Creteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou</name>
      <address>
        <city>France</city>
        <zip>75674</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de Bicêtre</name>
      <address>
        <city>le Kremlin Bicêtre</city>
        <zip>94275</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de l'Hôtel Dieu</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Tenon</name>
      <address>
        <city>Paris</city>
        <zip>75020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Hôtel Dieu</name>
      <address>
        <city>Paris</city>
        <zip>75181</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital pitié Salpetrière</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75674</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Bichat</name>
      <address>
        <city>Paris</city>
        <zip>75877</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Charles Nicoll</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Purpan</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>October 9, 2015</last_update_submitted>
  <last_update_submitted_qc>October 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 12, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV-1</keyword>
  <keyword>antiretroviral treatment</keyword>
  <keyword>viral load</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Viremia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raltegravir Potassium</mesh_term>
    <mesh_term>HIV Protease Inhibitors</mesh_term>
    <mesh_term>Protease Inhibitors</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02247687
org study id: ANRS 161 L-Vir
secondary id: 2014-001663-13
nct id: NCT02247687
lead sponsor: 
collaborator: 
has dmc: Yes
Management of participants with low-level persistent viremia
ANRS 161 L-Vir is a phase III prospective, randomized, multicenter, open-label, superiority
      trial for participants with low-level persistent viremia.

      Participants will be randomized with a 1:1:1 ratio to the following three arms,

        -  Reference arm : counseling without antiretroviral treatment modification

        -  Switch arm : switch of current PI/r for Prezista® (darunavir)/ Norvir® (ritonavir)
           (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with
           counseling.

        -  Addition of Isentress® (raltégravir) arm : Isentress® (raltegravir) 400 mg two times a
           day (BID) added to current antiretroviral treatment with counseling
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients in Virologic success by week 12
time frame: week 12
description: A virologic success is defined by a patient having plasma HIV-1 RNA levels <50 copies/ml at weeks 8 and 12.
measure: Proportion of participants with HIV-1 RNA < 50 copies/ml
time frame: week 4, week 8, week 12, week 24, week 36, week 48
measure: Proportion of participants with HIV-1 RNA < 20 copies/ml
time frame: week 4, week 8, week 12, week 24, week 36, week 48
measure: Proportion of participants with HIV-1 RNA <1copy/ml
time frame: week 8, week 12, week 24, week 36, week 48
measure: Change in CD4 cells count from baseline
time frame: week 12, week 24, week 48 and end visit
description: •Change was calculated as the CD4 count at the corresponding week minus the baseline CD4 count
measure: Number of Participants With Virologic Failure and Emergence of Resistance
time frame: day 0 and visit at failure time
description: •resistance patterns at failure time compared with day 0, in HIV-DNA and in HIV-RNA
measure: Quantification of HIV DNA in peripheral blood mononucleated cell (PBMC)
time frame: day 0
description: Quantification of HIV DNA in PBMC at day 0 and its association with the proportion of success in each arm
measure: Levels of antiretroviral drugs in plasma
time frame: day 0 and end visit
description: •plasma concentrations of antiretroviral drugs and correlation with success or failure of the strategy
measure: Levels of antiretroviral drugs in hair
time frame: day 0, week 12, week 24and end visit
description: •measurement of concentrations of antiretroviral drugs treatments in hair
measure: Levels of HIV-1 RNA in seminal plasma
time frame: day 0, week 12, week 48 and end visit
description: quantification of HIV RNA in seminal plasma
measure: Incidence of Study interruption
time frame: From day 0 to week 24
description: •proportion of participants who discontinued the strategy assigned by randomization at day 0 because of failure
measure: Incidence of clinical and biological adverse events
time frame: from day 0 to week 48
description: • proportions of participants experiencing a clinical or biological adverse events (ANRS scale)
measure: Self-reported adherence
time frame: day 0, week 4, week 8, week 12, week 24, week 36, week 48 and end visit
description: •self-reported percentage of antiretroviral treatment participant had taken during the last 4 weeks
arm group label: Counseling arm
arm group type: Other
description: Counseling without antiretroviral treatment modification
arm group label: Switch arm for protease inhibitor
arm group type: Active Comparator
description: Switch arm for protease inhibitor : intervention is the switch of current boosted protease inhibitor for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.
arm group label: Addition of Isentress® (raltegravir)
arm group type: Active Comparator
description: Drug: Addition of Isentress® (raltegravir) arm
• Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling
intervention type: Drug
intervention name: Protease inhibitor
description: Modification in the antiretroviral treatment
•Switch arm for protease inhibitor : intervention switch of current boosted protease inhibitor for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.
arm group label: Switch arm for protease inhibitor
other name: Prezista® / Norvir®
intervention type: Drug
intervention name: Isentress® (raltegravir)
description: • Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling
arm group label: Addition of Isentress® (raltegravir)
intervention type: Other
intervention name: Counseling arm
description: No change of antiretroviral treatment but only counseling
arm group label: Counseling arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jade Ghosn, MD, PhD
role: Principal Investigator
affiliation: APHP
facility: 
facility: 
facility: 
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facility: 
facility: 
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facility: 
facility: 
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country: France
responsible party type: Sponsor
mesh term: Viremia
mesh term: Raltegravir Potassium
mesh term: HIV Protease Inhibitors
mesh term: Protease Inhibitors