<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/NCT03244371</url>
  </required_header>
  <id_info>
    <org_study_id>2016-31</org_study_id>
    <secondary_id>2016-A01028-43</secondary_id>
    <nct_id>NCT03244371</nct_id>
  </id_info>
  <brief_title>Analysis of the Impact of HCV Treatment by Last Generation Direct Antiviral Agents (DAA) on Antiviral Immunity and HIV DNA Reservoir in Coinfected HIV-HCV Patients</brief_title>
  <acronym>HCURE</acronym>
  <official_title>Analysis of the Impact of HCV Treatment by Last Generation Direct Antiviral Agents (DAA) on Antiviral Immunity and HIV DNA Reservoir in Coinfected HIV-HCV Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</source>
  <oversight_info>
    <has_dmc>No</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>
      Spontaneous recovery of patients infected with HCV is related to the development of a&#xD;
      cytotoxic immune response that is executed by specialized white blood cells, the CD8+ T&#xD;
      cells, which develop a virus-specific response. In addition, the natural killer (NK) cells&#xD;
      provide a first-line innate cytotoxic response, which is pivotal for the spontaneous clearing&#xD;
      of HCV. In patients where HCV infection settles chronically, CD8+ T lymphocytes and NK cells&#xD;
      fall into a state of anergy induced by chronic viral challenge. This anergic state is also&#xD;
      found in the case of HIV infection and exacerbated by HIV-HCV coinfection. The first&#xD;
      therapeutic strategies against HCV were based on a treatment with interferon alpha, which had&#xD;
      an antiviral but also immunosuppressive effect. In fact, this therapeutic strategy was unable&#xD;
      to help the recovery of the patient's immune system that would be expected after HCV cure.&#xD;
      However, interferon-free therapeutic strategies combining first generation direct antiviral&#xD;
      agents (DAA) showed a positive effect on HCV antiviral immunity, by enhancing the&#xD;
      proliferative response of CD8+ T cells and the cytotoxic and proinflammatory responses of NK&#xD;
      cells in HCV monoinfected patients (4, 5). Since HCV-targeted therapies based on combinations&#xD;
      of the latest generation of DAA have nearly 100% cure rates and enable faster viral&#xD;
      suppression over shorter treatment times, a positive impact of these regimens on antiviral&#xD;
      immunity is plausible. This possibility would be particularly interesting in HIV-HCV&#xD;
      co-infected patients, where reactivation of the innate antiviral immunity may contribute to&#xD;
      immune defenses against both viruses. Moreover, it has been previously reported a moderate&#xD;
      but significant and sustained decline of HIV-1 DNA in CD4 T cells from HIV-1/hepatitis C&#xD;
      virus-coinfected patients receiving highly active antiretroviral therapy and treated with IFN&#xD;
      alpha/ribavirin.&#xD;
&#xD;
      To date, the real impact on antiviral immunity of treatment as well as on HIV reservoir with&#xD;
      the latest generation of DAA was not measured in HIV-HCV co-infected patients.&#xD;
&#xD;
      The aim of this study is to analyze the impact of the cure of hepatitis C on the HIV DNA&#xD;
      reservoir and antiviral function of CD8+ and NK cells in a subgroup of patients receiving the&#xD;
      latest generation DAAs for treatment of HCV infection, as part of a program for a reduction&#xD;
      of the prevalence of chronic hepatitis C patients co-infected HIV-HCV set up within the&#xD;
      Immuno-Hematology Service of the Sainte Marguerite Hospital (Research in routine care-Ethics&#xD;
      committee Approval Sud- Méditerranée I ID RCB 2015-A01913-46/ Principal Investigator: Dr I&#xD;
      Poizot-Martin).&#xD;
&#xD;
      The analysis of HIV DNA, NK and CD8+ T lymphocyte antiviral immune response prior, during and&#xD;
      after anti-HCV treatment will need the collection of a biobank. Indeed, 25 mL peripheral&#xD;
      blood will be collected at treatment initiation, during an interim assessment, at the end of&#xD;
      treatment and six months post-treatment, for a total of 100 ml of additional blood&#xD;
      collection. These analyzes will be performed by Dr C Tamalet for HIV DNA IHU-Méditerranée&#xD;
      Infection, and the team of Prof. E Vivier, DHU- Marseille Immunopole for NK and CD8+ T&#xD;
      lymphocyte antiviral immune response.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 31, 2016</start_date>
  <completion_date type="Anticipated">February 28, 2019</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>number of CD8+ at each time point of the treatment</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>number of NK cells at each time point of the treatment</measure>
    <time_frame>24 month</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>HIV Associated HCV</condition>
  <arm_group>
    <arm_group_label>Co infected HIV and HCV patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood draw</intervention_name>
    <description>4 blood draws of 25 mls of blood will be performed at 4 differents time points (before treatment, 4 weeks later, at the end of the treatment and 6 months after the end of the treatment)</description>
    <arm_group_label>Co infected HIV and HCV patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV1 infected patient&#xD;
&#xD;
          -  HCV positive serologie and RNA-HCV positive&#xD;
&#xD;
          -  Starting an anti-HCV traitment with direct antiviral agent&#xD;
&#xD;
          -  With an hepatic fibrosis score &lt; 12,5KPa measured through elastometry or with a score&#xD;
             &lt; F4 from liver biopsy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV2 infected patients par le VIH2&#xD;
&#xD;
          -  Positive for HBsAg,&#xD;
&#xD;
          -  Cirrohtic patient (elastométry &gt;12,5kPa or métavir score F4)&#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>Urielle DESALBRES</last_name>
    <role>Study Director</role>
    <affiliation>AP-HM</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Isabelle POIZOT-MARTIN, MD</last_name>
    <phone>+33491746163</phone>
    <email>isabelle.poizot@ap-hm.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Assistance Publique Hôpitaux de Marseille</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle POIZOT-MARTIN, MD</last_name>
      <phone>+33491746163</phone>
      <email>isabelle.poizot@ap-hm.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>August 7, 2017</last_update_submitted>
  <last_update_submitted_qc>August 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03244371
org study id: 2016-31
secondary id: 2016-A01028-43
nct id: NCT03244371
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Spontaneous recovery of patients infected with HCV is related to the development of a
      cytotoxic immune response that is executed by specialized white blood cells, the CD8+ T
      cells, which develop a virus-specific response. In addition, the natural killer (NK) cells
      provide a first-line innate cytotoxic response, which is pivotal for the spontaneous clearing
      of HCV. In patients where HCV infection settles chronically, CD8+ T lymphocytes and NK cells
      fall into a state of anergy induced by chronic viral challenge. This anergic state is also
      found in the case of HIV infection and exacerbated by HIV-HCV coinfection. The first
      therapeutic strategies against HCV were based on a treatment with interferon alpha, which had
      an antiviral but also immunosuppressive effect. In fact, this therapeutic strategy was unable
      to help the recovery of the patient's immune system that would be expected after HCV cure.
      However, interferon-free therapeutic strategies combining first generation direct antiviral
      agents (DAA) showed a positive effect on HCV antiviral immunity, by enhancing the
      proliferative response of CD8+ T cells and the cytotoxic and proinflammatory responses of NK
      cells in HCV monoinfected patients (4, 5). Since HCV-targeted therapies based on combinations
      of the latest generation of DAA have nearly 100% cure rates and enable faster viral
      suppression over shorter treatment times, a positive impact of these regimens on antiviral
      immunity is plausible. This possibility would be particularly interesting in HIV-HCV
      co-infected patients, where reactivation of the innate antiviral immunity may contribute to
      immune defenses against both viruses. Moreover, it has been previously reported a moderate
      but significant and sustained decline of HIV-1 DNA in CD4 T cells from HIV-1/hepatitis C
      virus-coinfected patients receiving highly active antiretroviral therapy and treated with IFN
      alpha/ribavirin.

      To date, the real impact on antiviral immunity of treatment as well as on HIV reservoir with
      the latest generation of DAA was not measured in HIV-HCV co-infected patients.

      The aim of this study is to analyze the impact of the cure of hepatitis C on the HIV DNA
      reservoir and antiviral function of CD8+ and NK cells in a subgroup of patients receiving the
      latest generation DAAs for treatment of HCV infection, as part of a program for a reduction
      of the prevalence of chronic hepatitis C patients co-infected HIV-HCV set up within the
      Immuno-Hematology Service of the Sainte Marguerite Hospital (Research in routine care-Ethics
      committee Approval Sud- Méditerranée I ID RCB 2015-A01913-46/ Principal Investigator: Dr I
      Poizot-Martin).

      The analysis of HIV DNA, NK and CD8+ T lymphocyte antiviral immune response prior, during and
      after anti-HCV treatment will need the collection of a biobank. Indeed, 25 mL peripheral
      blood will be collected at treatment initiation, during an interim assessment, at the end of
      treatment and six months post-treatment, for a total of 100 ml of additional blood
      collection. These analyzes will be performed by Dr C Tamalet for HIV DNA IHU-Méditerranée
      Infection, and the team of Prof. E Vivier, DHU- Marseille Immunopole for NK and CD8+ T
      lymphocyte antiviral immune response.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: number of CD8+ at each time point of the treatment
time frame: 24 months
measure: number of NK cells at each time point of the treatment
time frame: 24 month
arm group label: Co infected HIV and HCV patients
arm group type: Experimental
intervention type: Other
intervention name: blood draw
description: 4 blood draws of 25 mls of blood will be performed at 4 differents time points (before treatment, 4 weeks later, at the end of the treatment and 6 months after the end of the treatment)
arm group label: Co infected HIV and HCV patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Urielle DESALBRES
role: Study Director
affiliation: AP-HM
last name: Isabelle POIZOT-MARTIN, MD
phone: +33491746163
email: isabelle.poizot@ap-hm.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
sharing ipd: Undecided