<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/NCT03256422</url>
  </required_header>
  <id_info>
    <org_study_id>ANRS 170 - QUATUOR</org_study_id>
    <nct_id>NCT03256422</nct_id>
  </id_info>
  <brief_title>Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients</brief_title>
  <acronym>QUATUOR</acronym>
  <official_title>Randomized, Open-label and Multicentric Trial Evaluating the Non-inferiority of Antiretroviral Treatment Taken 4 Consecutive Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients With Controlled Viral Load Under Antiretroviral Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ANRS, Emerging Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>IMEA Leon M'Ba Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Unit 1136 INSERM, Faculty of medecine, University Pierre and Marie Curie</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>ANRS, Emerging Infectious Diseases</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups,&#xD;
      evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a&#xD;
      week versus continuous therapy, in HIV infected patients with controlled viral load for at&#xD;
      least 12 months and stable antiretroviral treatment since 4 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at&#xD;
      W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus&#xD;
      continuous therapy, in HIV infected patients with controlled viral load for at least 12&#xD;
      months and stable antiretroviral treatment since 4 months. The non-inferiority margin (delta)&#xD;
      is 5%. The randomization will be stratified according to the family of the third&#xD;
      antiretroviral agent (II, PI, and NNRTI). A minimum of 200 patients will be included in the&#xD;
      integrase inhibitor strata to provide a sufficient power to assess the efficacy of strategy&#xD;
      in this population.&#xD;
&#xD;
      At W48, all patients with virological success in the continuous therapy group will switch to&#xD;
      the 4/7 days therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 7, 2017</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</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>
    <intervention_model_description>Open-label, randomized trial in 2 parallel groups</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients with therapeutic success at Week 48.</measure>
    <time_frame>Week 48</time_frame>
    <description>To evaluate after 48 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by :&#xD;
absence of virological failure : a measure of the viral load will be done, this measure have to be &lt; 50 cp/mL. If it's &gt; 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still &gt; 50 cp/mL, it's a virological failure&#xD;
no discontinuation or modification of the study strategy for more than 30 consecutive days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with therapeutic success at Week 96</measure>
    <time_frame>Week 96</time_frame>
    <description>To evaluate after 96 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by :&#xD;
absence of virological failure : a measure of the viral load will be done, this measure have to be &lt; 50 cp/mL. If it's &gt; 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still &gt; 50 cp/mL, it's a virological failure&#xD;
no discontinuation or modification of the study strategy for more than 30 consecutive days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Virological success</measure>
    <time_frame>Week 48 and Week 96</time_frame>
    <description>The HIV-1 viral load at week 48 must be inferior to 50 copies/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of virological &quot; blips &quot;</measure>
    <time_frame>between Week 0 and Week 48, and between Week 0 and Week 96</time_frame>
    <description>viral load &gt; 50 copies/mL followed by a control value ≤ 50 cp/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with a viral load signal detected</measure>
    <time_frame>between Week 0 and Week 48 and Week 0 and Week 96</time_frame>
    <description>(subgroup of patients tested with Roche-Taqman, threshold&lt;20 copies/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by next generation sequencing</measure>
    <time_frame>Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of minority resistant variants archived in DNA at Week 0 and their impact on virological failure (2 consecutive VL&gt; 50 copies / mL) and on the acquisition of drugs resistance mutations</measure>
    <time_frame>Week 0</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of ultra sensitive viral load and total DNA in the peripheral blood mononuclear cells at Week 0, Week 24, Week 48 and Week 96; evolution of viral genotypic sequence between Week 0, Week 48 and Week 96 (subgroup of 120 patients)</measure>
    <time_frame>between Week 0, Week 48 and Week 96</time_frame>
    <description>Immuno-viro-pharmacological sub-study of 120 patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description of the factors associated with virological rebound (viral load &gt;50 cp/mL).</measure>
    <time_frame>Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary)</time_frame>
    <description>(viral load &gt;50 cp/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of T cluster of differentiation 4 and cluster of differentiation 8 cells count, and T cluster of differentiation 4 /cluster of differentiation 8 ratio</measure>
    <time_frame>from Week-4 to Week 48 and Week 96</time_frame>
    <description>Measurement of T cluster of differentiation 4 cell count, T cluster of differentiation 8 cell count, and T cluster of differentiation 4 /T cluster of differentiation 8 ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of fasting metabolic parameters</measure>
    <time_frame>until Week 48 and Week 96</time_frame>
    <description>Measurement of total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of inflammation and immune activation parameters</measure>
    <time_frame>from Week 0 to Week 24 and Week 48</time_frame>
    <description>Measurement of sCD14, sCD163, IP-10, C-reactive protein, interleukin-6 et D-dimerus, soluble TNF receptor 1, soluble TNF receptor 2 Immuno-viro-Pharmacological Sub-study in 120 patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV RNA viral load in semen</measure>
    <time_frame>Week 0, Week 24 and Week 48</time_frame>
    <description>Sperm sub-study (120 patients)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual plasmatic concentrations of the third antiretroviral agent</measure>
    <time_frame>Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96</time_frame>
    <description>Measurement of the third antiretroviral agent plasmatic concentration (protease inhibitors or non-nucleoside reverse transcriptase inhibitors or integrase inhibitors)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual plasmatic concentrations of tenofovir (TDF or TAF)</measure>
    <time_frame>Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96</time_frame>
    <description>Measurement of tenofovir plasmatic concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual intracellular concentrations of the third antiretroviral agents</measure>
    <time_frame>Week 0, Week 24 and Week 48</time_frame>
    <description>Immuno-viro-Pharmacological sub-study (120 patients) Measurement of the third antiretroviral agent intracellular concentration (protease inhibitors or non-nucleoside reverse transcriptase inhibitors or integrase inhibitors)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment adherence</measure>
    <time_frame>Week 0, Week 12, Week 24, Week 36, Week 48, Week 72,and Week 96</time_frame>
    <description>Evaluation by a self-reported questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>Week-4, Week 0, Week 48 and Week 96</time_frame>
    <description>Evaluation by a self-reported questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>Week 0, Week 12, Week 48 and Week 96</time_frame>
    <description>Evaluation by a self-reported questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmaco-economic aspects of the strategy</measure>
    <time_frame>Between Week 0 and Week 98</time_frame>
    <description>Assessment and comparison of cost essay between each arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median time to virologic failure</measure>
    <time_frame>Between week 0 and 98</time_frame>
    <description>Measure the delay between week 0 and the date of different virologic failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE)</measure>
    <time_frame>Between Week 0 and Week 98</time_frame>
    <description>according to the sponsor's grading scale</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">640</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>4 days / 7</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients included in this arm will take their ARV treatment 4 consecutive days per week during 98 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>7 days / 7</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients included in this arm will continue their ARV therapy 7 days per weeks during 48 weeks and after W48, they will take their ARV treatment 4 days per week until W98</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment discontinuation</intervention_name>
    <description>• Receiving tritherapy. Allowed treatment drugs are :&#xD;
nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine&#xD;
protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r&#xD;
non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine&#xD;
integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir</description>
    <arm_group_label>4 days / 7</arm_group_label>
    <arm_group_label>7 days / 7</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infection, coinfection HIV-1/HIV-2 possible&#xD;
&#xD;
          -  Age≥18 years old&#xD;
&#xD;
          -  Current therapy unchanged for the last 4 months&#xD;
&#xD;
          -  Receiving tritherapy with 2 nucleoside reverse transcriptase inhibitor+protease&#xD;
             inhibitors or 2 nucleoside reverse transcriptase inhibitor+non-nucleoside reverse&#xD;
             transcriptase inhibitors or 2 nucleoside reverse transcriptase inhibitor+integrase&#xD;
             inhibitors.&#xD;
&#xD;
        Allowed treatment drugs are :&#xD;
&#xD;
        1. nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine 2.&#xD;
        protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r 3. Non nucleoside reverse&#xD;
        transcriptase inhibitors : efavirenz, rilpivirine ou etravirine 4. integrase inhibitors :&#xD;
        dolutegravir, elvitegravir/cobicistat ou raltegravir&#xD;
&#xD;
          -  Viruses susceptible to all antiretroviral drugs present in the ongoing tritherapy&#xD;
             (AC11-ANRS algorithm).&#xD;
&#xD;
               1. If a genotype is available in the patient medical history; viruses must be&#xD;
                  susceptible to all ongoing antiretroviral drugs&#xD;
&#xD;
               2. If no RNA genotype available, a genotype will be performed on DNA at screening&#xD;
                  and will not have to show any resistance to the ongoing antiretroviral drugs&#xD;
&#xD;
          -  Viral load (VL) &lt; 50 cp/mL in the past year, with at least 3 VL measurements including&#xD;
             screening; only one episode of viral blip &lt; 200 copies/mL is authorized in the last&#xD;
             year&#xD;
&#xD;
          -  CD4 T cells &gt; 250/mm3 at the screening visit&#xD;
&#xD;
          -  Estimated glomerular filtration rate &gt; 60 mL/min (Chronic Kidney Disease -&#xD;
             Epidemiology Collaboration method)&#xD;
&#xD;
          -  Transaminases : aspartate aminotransférase et alanine aminotransférase &lt; 3N&#xD;
&#xD;
          -  Haemoglobin &gt; 10 g/dL&#xD;
&#xD;
          -  Platelets &gt; 100 000/mm3&#xD;
&#xD;
          -  For women of childbearing age, negative pregnancy test at screening; agree to use&#xD;
             mechanical contraception during the study&#xD;
&#xD;
          -  Social security system coverage&#xD;
&#xD;
          -  Informed consent form signed by patient and investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infection by HIV-2&#xD;
&#xD;
          -  Chronic and active Viral B Hepatitis with positive antigen HBs&#xD;
&#xD;
          -  Chronic and active Viral C Hepatitis with treatment expected in the next 98 weeks&#xD;
&#xD;
          -  Concomitant treatment using interferon, interleukins, any other immune-therapy or&#xD;
             chemotherapy, antivitaminK for patients on ARVT using a booster&#xD;
&#xD;
          -  Concomitant prophylactic or curative treatment for an opportunistic infection&#xD;
&#xD;
          -  All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly&#xD;
             interfere with study protocol compliance, observance and/or study treatment tolerance&#xD;
&#xD;
          -  Pregnant or breast feeding women&#xD;
&#xD;
          -  Subjects under &quot;sauvegarde de justice&quot; (judicial protection due to temporarily and&#xD;
             slightly diminished mental or physical faculties), or under legal guardianship&#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>Pierre De Truchis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Raymond Poincaré</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Pointe-à-Pitre</name>
      <address>
        <city>Pointe-à-Pitre</city>
        <state>Guadeloupe</state>
        <zip>97159</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital La Meynard Zobda Quitman</name>
      <address>
        <city>Fort-de-France</city>
        <state>Martinique</state>
        <zip>97261</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier Victor Dupouy</name>
      <address>
        <city>Argenteuil</city>
        <zip>95100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Henri Duffaut</name>
      <address>
        <city>Avignon</city>
        <zip>84000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Jean Minjoz</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avicenne</name>
      <address>
        <city>Bobigny</city>
        <zip>93000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>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 Ambroise Paré</name>
      <address>
        <city>Boulogne-Billancourt</city>
        <zip>92104</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 Louis Pasteur</name>
      <address>
        <city>Chartres</city>
        <zip>28630</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoine Beclère</name>
      <address>
        <city>Clamart</city>
        <zip>92140</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Gabriel Montpied</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier sud francilien</name>
      <address>
        <city>Corbeil-Essonnes</city>
        <zip>91106</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI de Créteil</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Henri Mondor</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital du Bocage</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Raymond Poincaré</name>
      <address>
        <city>Garches</city>
        <zip>92380</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Michallon</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bicêtre</name>
      <address>
        <city>Kremlin Bicêtre</city>
        <zip>94275</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHD de la Roche Sur Yon</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <zip>85295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier du Mans</name>
      <address>
        <city>Le Mans</city>
        <zip>72037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut hospitalier franco-britannique</name>
      <address>
        <city>Levallois-Perret</city>
        <zip>92309</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Dupuytren</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Croix Rousse</name>
      <address>
        <city>Lyon</city>
        <zip>69000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69437</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Sainte Marguerite</name>
      <address>
        <city>Marseille</city>
        <zip>13274</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen</name>
      <address>
        <city>Marseille</city>
        <zip>13331</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Gui de Chauliac</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Emile Müller</name>
      <address>
        <city>Mulhouse</city>
        <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 de l'Archet</name>
      <address>
        <city>Nice</city>
        <zip>06202</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Carémeau</name>
      <address>
        <city>Nîmes</city>
        <zip>30029</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de La Source</name>
      <address>
        <city>Orléans</city>
        <zip>45100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Antoine</name>
      <address>
        <city>Paris</city>
        <zip>75012</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 Bichat</name>
      <address>
        <city>Paris</city>
        <zip>75018</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de l'Hôtel Dieu</name>
      <address>
        <city>Paris</city>
        <zip>75181</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôtel-Dieu</name>
      <address>
        <city>Paris</city>
        <zip>75181</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>Lariboisière</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75908</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tenon</name>
      <address>
        <city>Paris</city>
        <zip>75970</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Perpignan</name>
      <address>
        <city>Perpignan</city>
        <zip>66046</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier René Dubos</name>
      <address>
        <city>Pontoise</city>
        <zip>95301</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier Annecy Genevois</name>
      <address>
        <city>Pringy</city>
        <zip>74374</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Robert Debré</name>
      <address>
        <city>Reims</city>
        <zip>51100</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>Centre Hospitalier de Saint-Brieuc</name>
      <address>
        <city>Saint-Brieuc</city>
        <zip>22000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Delafontaine</name>
      <address>
        <city>Saint-Denis</city>
        <zip>93205</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Général de Saint Nazaire</name>
      <address>
        <city>Saint-Nazaire</city>
        <zip>44600</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Nord</name>
      <address>
        <city>Saint-Étienne</city>
        <zip>42055</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Civil</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Foch</name>
      <address>
        <city>Suresnes</city>
        <zip>92151</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital La Grave</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</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>
    <facility>
      <name>Hôpital Gustave Dron</name>
      <address>
        <city>Tourcoing</city>
        <zip>59208</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Bretonneau</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de Brabois</name>
      <address>
        <city>Vandoeuvre les Nancy cedex</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital André Mignot</name>
      <address>
        <city>Versailles</city>
        <zip>78157</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Intercommunal</name>
      <address>
        <city>Villeneuve-Saint-Georges</city>
        <zip>94195</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>February 2, 2018</last_update_submitted>
  <last_update_submitted_qc>February 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Controlled, virological and therapeutic success, treatment discontinution, 4 days per week</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_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/NCT03256422
org study id: ANRS 170 - QUATUOR
nct id: NCT03256422
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups,
      evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a
      week versus continuous therapy, in HIV infected patients with controlled viral load for at
      least 12 months and stable antiretroviral treatment since 4 months.
Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at
      W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus
      continuous therapy, in HIV infected patients with controlled viral load for at least 12
      months and stable antiretroviral treatment since 4 months. The non-inferiority margin (delta)
      is 5%. The randomization will be stratified according to the family of the third
      antiretroviral agent (II, PI, and NNRTI). A minimum of 200 patients will be included in the
      integrase inhibitor strata to provide a sufficient power to assess the efficacy of strategy
      in this population.

      At W48, all patients with virological success in the continuous therapy group will switch to
      the 4/7 days therapy.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open-label, randomized trial in 2 parallel groups
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients with therapeutic success at Week 48.
time frame: Week 48
description: To evaluate after 48 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by :
absence of virological failure : a measure of the viral load will be done, this measure have to be < 50 cp/mL. If it's > 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still > 50 cp/mL, it's a virological failure
no discontinuation or modification of the study strategy for more than 30 consecutive days.
measure: Proportion of patients with therapeutic success at Week 96
time frame: Week 96
description: To evaluate after 96 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by :
absence of virological failure : a measure of the viral load will be done, this measure have to be < 50 cp/mL. If it's > 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still > 50 cp/mL, it's a virological failure
no discontinuation or modification of the study strategy for more than 30 consecutive days.
measure: Virological success
time frame: Week 48 and Week 96
description: The HIV-1 viral load at week 48 must be inferior to 50 copies/mL
measure: Number of virological " blips "
time frame: between Week 0 and Week 48, and between Week 0 and Week 96
description: viral load > 50 copies/mL followed by a control value ≤ 50 cp/mL
measure: Percentage of patients with a viral load signal detected
time frame: between Week 0 and Week 48 and Week 0 and Week 96
description: (subgroup of patients tested with Roche-Taqman, threshold<20 copies/mL)
measure: Proportion of patients with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by next generation sequencing
time frame: Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary)
measure: Frequency of minority resistant variants archived in DNA at Week 0 and their impact on virological failure (2 consecutive VL> 50 copies / mL) and on the acquisition of drugs resistance mutations
time frame: Week 0
measure: Evolution of ultra sensitive viral load and total DNA in the peripheral blood mononuclear cells at Week 0, Week 24, Week 48 and Week 96; evolution of viral genotypic sequence between Week 0, Week 48 and Week 96 (subgroup of 120 patients)
time frame: between Week 0, Week 48 and Week 96
description: Immuno-viro-pharmacological sub-study of 120 patients
measure: Description of the factors associated with virological rebound (viral load >50 cp/mL).
time frame: Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary)
description: (viral load >50 cp/mL).
measure: Evolution of T cluster of differentiation 4 and cluster of differentiation 8 cells count, and T cluster of differentiation 4 /cluster of differentiation 8 ratio
time frame: from Week-4 to Week 48 and Week 96
description: Measurement of T cluster of differentiation 4 cell count, T cluster of differentiation 8 cell count, and T cluster of differentiation 4 /T cluster of differentiation 8 ratio
measure: Evolution of fasting metabolic parameters
time frame: until Week 48 and Week 96
description: Measurement of total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia
measure: Evolution of inflammation and immune activation parameters
time frame: from Week 0 to Week 24 and Week 48
description: Measurement of sCD14, sCD163, IP-10, C-reactive protein, interleukin-6 et D-dimerus, soluble TNF receptor 1, soluble TNF receptor 2 Immuno-viro-Pharmacological Sub-study in 120 patients
measure: HIV RNA viral load in semen
time frame: Week 0, Week 24 and Week 48
description: Sperm sub-study (120 patients)
measure: Residual plasmatic concentrations of the third antiretroviral agent
time frame: Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96
description: Measurement of the third antiretroviral agent plasmatic concentration (protease inhibitors or non-nucleoside reverse transcriptase inhibitors or integrase inhibitors)
measure: Residual plasmatic concentrations of tenofovir (TDF or TAF)
time frame: Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96
description: Measurement of tenofovir plasmatic concentration
measure: Residual intracellular concentrations of the third antiretroviral agents
time frame: Week 0, Week 24 and Week 48
description: Immuno-viro-Pharmacological sub-study (120 patients) Measurement of the third antiretroviral agent intracellular concentration (protease inhibitors or non-nucleoside reverse transcriptase inhibitors or integrase inhibitors)
measure: Treatment adherence
time frame: Week 0, Week 12, Week 24, Week 36, Week 48, Week 72,and Week 96
description: Evaluation by a self-reported questionnaire
measure: Quality of life
time frame: Week-4, Week 0, Week 48 and Week 96
description: Evaluation by a self-reported questionnaire
measure: Patient satisfaction
time frame: Week 0, Week 12, Week 48 and Week 96
description: Evaluation by a self-reported questionnaire
measure: Pharmaco-economic aspects of the strategy
time frame: Between Week 0 and Week 98
description: Assessment and comparison of cost essay between each arm.
measure: Median time to virologic failure
time frame: Between week 0 and 98
description: Measure the delay between week 0 and the date of different virologic failure
measure: Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE)
time frame: Between Week 0 and Week 98
description: according to the sponsor's grading scale
arm group label: 4 days / 7
arm group type: Experimental
description: Patients included in this arm will take their ARV treatment 4 consecutive days per week during 98 weeks
arm group label: 7 days / 7
arm group type: Active Comparator
description: Patients included in this arm will continue their ARV therapy 7 days per weeks during 48 weeks and after W48, they will take their ARV treatment 4 days per week until W98
intervention type: Drug
intervention name: Treatment discontinuation
description: • Receiving tritherapy. Allowed treatment drugs are :
nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine
protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r
non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine
integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir
arm group label: 4 days / 7
arm group label: 7 days / 7
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pierre De Truchis, MD
role: Principal Investigator
affiliation: Hôpital Raymond Poincaré
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country: France
responsible party type: Sponsor
mesh term: HIV Infections