<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/NCT03789513</url>
  </required_header>
  <id_info>
    <org_study_id>ANRS12375 AIMA-CC</org_study_id>
    <nct_id>NCT03789513</nct_id>
  </id_info>
  <brief_title>Evaluation of Triage Options After HPV Testing for Cervical Cancer Screening Among HIV-infected Women</brief_title>
  <acronym>AIMA-CC</acronym>
  <official_title>Evaluation of Screening Algorithms Based on Self-collection and HPV Testing With Partial Genotyping for the Prevention of Cervical Cancer Among HIV-infected Women in Low-income Countries</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ANRS, Emerging Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut de Recherche pour le Developpement</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>International Agency for Research on Cancer</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Geneva</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Bordeaux</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>ANRS, Emerging Infectious Diseases</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>
      Cervical cancer is the most common cause of cancer and a leading cause of death among&#xD;
      HIV-infected women living in resource-limited settings. Although screening for premalignant&#xD;
      lesions is an effective way of reducing cervical cancer incidence, its uptake in low-resource&#xD;
      settings to date is low. The use of HPV testing for primary screening is currently&#xD;
      recommended by many guidelines - including the WHO guidelines for cervical cancer screening&#xD;
      in resource-limited settings - because of its greater sensitivity and ease of use compared to&#xD;
      other options. However, these WHO guidelines have both highlighted the need to conduct more&#xD;
      research on appropriate HPV-based algorithms among HIV-infected women, as immunodeficiency&#xD;
      may affect the screening performance. Indeed, HPV infections in HIV-infected women are very&#xD;
      common, so there is a need for additional triage to identify women most at risk and there&#xD;
      remains considerable uncertainty on the optimal option for such triage. Most of the evidence&#xD;
      available comes from HIV-negative populations living in high-resource settings and is not&#xD;
      necessarily relevant for low-resource contexts where the epidemiological background is&#xD;
      different, women access late to screening and may not have follow up visits, where financial&#xD;
      constraints are important and health service resources limited.&#xD;
&#xD;
      Hence, the proposed project aims to provide evidence on the effectiveness and feasibility of&#xD;
      HPV-based screening algorithms among HIV-infected women in low-resource settings.&#xD;
&#xD;
      This multicenter cross-sectional study will include 3,000 HIV-infected women (30-49 years&#xD;
      old) receiving HAART and followed in Abidjan (Ivory Coast), Bobo-Dioulasso (Burkina Faso) and&#xD;
      Phnom Penh (Cambodia).&#xD;
&#xD;
      After self-collection of cervico-vaginal samples, each participant will have an HPV test with&#xD;
      partial genotyping primary using the Xpert HPV assay, a real-time PCR assay that provides the&#xD;
      possibility of identifying 14 HR-HPV types within one hour. The Xpert HPV test has been&#xD;
      chosen because of the wide availability of the Genexpert platform in HIV care centers from&#xD;
      resource-limited settings. Furthermore, it can specifically detect HPV-16, 18 and 45, the&#xD;
      most carcinogenic HPV types in both HIV-negative and HIV-positive women, separately from&#xD;
      other high-risk HPV types. VIA will be another triage option either alone or combined to HPV&#xD;
      DNA genotyping.&#xD;
&#xD;
      In addition, participants treated for cervical lesion will be followed over 12 months to&#xD;
      assess the risk of post-treatment lesions (CIN2+/HSIL) and to identify associated&#xD;
      risk-factors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2022</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>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensitivity of the triage options</measure>
    <time_frame>Day 0</time_frame>
    <description>Sensitivity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specificity of the triage options</measure>
    <time_frame>Day 0</time_frame>
    <description>Specificity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Positive and negative predictive value (PPV and NPV) of the triage options</measure>
    <time_frame>Day 0</time_frame>
    <description>PPV and NPV of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive and negative diagnostic likelihood ratio (DLR) of the triage options</measure>
    <time_frame>Day 0</time_frame>
    <description>Positive and negative DLR of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability and feasibility</measure>
    <time_frame>Day 0 and Week 1</time_frame>
    <description>Acceptability and feasibility of the self-sampling, of the different triage options and of the treatment cervical lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of CIN2+ lesions</measure>
    <time_frame>Day 0</time_frame>
    <description>Prevalence of CIN2 lesions, overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of CIN3+ lesions</measure>
    <time_frame>Day 0</time_frame>
    <description>Prevalence of CIN3 lesions overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of cervical cancer</measure>
    <time_frame>Day 0</time_frame>
    <description>Prevalence of cervical cancer overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Day 0 and Week 1 up to 24 weeks</time_frame>
    <description>Rate and nature of adverse events and protocol violations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of the women eligible to HPV screening who were actually screened and treated (if required)</measure>
    <time_frame>Day 0</time_frame>
    <description>Proportion of the women eligible for the study who were actually screened, treated (if required)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the micro-costing</measure>
    <time_frame>Day 0 up to Week 26</time_frame>
    <description>Evaluation of the micro-costing of the various components of the screening strategies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of post-treatment HPV clearance</measure>
    <time_frame>Week 24 and 48 post treatment</time_frame>
    <description>Evaluation of the HPV clearance at M6 and M12 after thermal-ablation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of post-treatment cervical lesion</measure>
    <time_frame>Week 48 post treatment</time_frame>
    <description>Evaluation of the proportion of CIN2 and CIN3 at M12 after treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">3000</enrollment>
  <condition>HIV Infections</condition>
  <condition>HPV - Anogenital Human Papilloma Virus Infection</condition>
  <arm_group>
    <arm_group_label>Triage with different options</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All women will have an HPV test, partial genotyping (16/18/45 versus other high-risk HPV [hr-HPV]) and VIA. The different options for triage that will be compared are:&#xD;
Participants hr-HVP+ and VIA+ participants selected for treatment;&#xD;
Participants HPV 16/18/45+ selected for treatment;&#xD;
Participant HPV 16/18/45+ and/or VIA+ selected for treatment;</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>HPV test with partial genotyping and VIA triage</intervention_name>
    <description>HPV testing with the GenXpert platform VIA Biopsies of VIA+ lesions or random Treatment with thermal ablation of women with precancerous lesions</description>
    <arm_group_label>Triage with different options</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women&#xD;
&#xD;
          -  HIV-1 infection&#xD;
&#xD;
          -  Age 30 to 49 years&#xD;
&#xD;
          -  In care for HIV infection, receiving or initiating antiretroviral therapy&#xD;
&#xD;
          -  Written informed consent given&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV-2 infection&#xD;
&#xD;
          -  Ongoing pregnancy (evidenced by self-report or clinical examination)&#xD;
&#xD;
          -  Previous total hysterectomy&#xD;
&#xD;
          -  Severe concomitant disease that, according to the investigators, may contraindicate or&#xD;
             compromise participation to the study&#xD;
&#xD;
          -  History of cervical cancer screening with treatment for precancerous lesions within&#xD;
             the last 12 months&#xD;
&#xD;
        Differed inclusion&#xD;
&#xD;
          -  Ongoing heavy menstruation&#xD;
&#xD;
          -  Immediate post-partum (&lt;12 weeks post delivery)&#xD;
&#xD;
          -  Sign of ongoing genital infection (e.g. mucopurulante discharge)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pierre Debeaudrap, PhD</last_name>
    <role>Study Director</role>
    <affiliation>CEPED - UMR196</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Apollinaire Debeaudrap, PhD</last_name>
    <role>Study Director</role>
    <affiliation>PACCI - Ivory Coast</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pierre Debeaudrap, PhD</last_name>
    <phone>(0) 1 76 53 34 53</phone>
    <phone_ext>+33</phone_ext>
    <email>pierre.debeaudrap@ird.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Apollinaire Horo, PhD</last_name>
    <email>horoapollinaire@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>HIV day care center</name>
      <address>
        <city>Bobo-Dioulasso</city>
        <country>Burkina Faso</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Armel Poda</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Calmette Hospital</name>
      <address>
        <city>Phnom Penh</city>
        <country>Cambodia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kim Sothea</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CEPREF</name>
      <address>
        <city>Abidjan</city>
        <country>Côte D'Ivoire</country>
      </address>
    </facility>
    <status>Enrolling by invitation</status>
  </location>
  <location_countries>
    <country>Burkina Faso</country>
    <country>Cambodia</country>
    <country>Côte D'Ivoire</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV infection, HPV infection, cervical cancer, screening algorithms</keyword>
  <keyword>recurrence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Papillomavirus Infections</mesh_term>
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Papilloma</mesh_term>
  </condition_browse>
  <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/NCT03789513
org study id: ANRS12375 AIMA-CC
nct id: NCT03789513
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cervical cancer is the most common cause of cancer and a leading cause of death among
      HIV-infected women living in resource-limited settings. Although screening for premalignant
      lesions is an effective way of reducing cervical cancer incidence, its uptake in low-resource
      settings to date is low. The use of HPV testing for primary screening is currently
      recommended by many guidelines - including the WHO guidelines for cervical cancer screening
      in resource-limited settings - because of its greater sensitivity and ease of use compared to
      other options. However, these WHO guidelines have both highlighted the need to conduct more
      research on appropriate HPV-based algorithms among HIV-infected women, as immunodeficiency
      may affect the screening performance. Indeed, HPV infections in HIV-infected women are very
      common, so there is a need for additional triage to identify women most at risk and there
      remains considerable uncertainty on the optimal option for such triage. Most of the evidence
      available comes from HIV-negative populations living in high-resource settings and is not
      necessarily relevant for low-resource contexts where the epidemiological background is
      different, women access late to screening and may not have follow up visits, where financial
      constraints are important and health service resources limited.

      Hence, the proposed project aims to provide evidence on the effectiveness and feasibility of
      HPV-based screening algorithms among HIV-infected women in low-resource settings.

      This multicenter cross-sectional study will include 3,000 HIV-infected women (30-49 years
      old) receiving HAART and followed in Abidjan (Ivory Coast), Bobo-Dioulasso (Burkina Faso) and
      Phnom Penh (Cambodia).

      After self-collection of cervico-vaginal samples, each participant will have an HPV test with
      partial genotyping primary using the Xpert HPV assay, a real-time PCR assay that provides the
      possibility of identifying 14 HR-HPV types within one hour. The Xpert HPV test has been
      chosen because of the wide availability of the Genexpert platform in HIV care centers from
      resource-limited settings. Furthermore, it can specifically detect HPV-16, 18 and 45, the
      most carcinogenic HPV types in both HIV-negative and HIV-positive women, separately from
      other high-risk HPV types. VIA will be another triage option either alone or combined to HPV
      DNA genotyping.

      In addition, participants treated for cervical lesion will be followed over 12 months to
      assess the risk of post-treatment lesions (CIN2+/HSIL) and to identify associated
      risk-factors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Sensitivity of the triage options
time frame: Day 0
description: Sensitivity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard
measure: Specificity of the triage options
time frame: Day 0
description: Specificity of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard
measure: Positive and negative predictive value (PPV and NPV) of the triage options
time frame: Day 0
description: PPV and NPV of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard
measure: Positive and negative diagnostic likelihood ratio (DLR) of the triage options
time frame: Day 0
description: Positive and negative DLR of the triage options to detect CIN2+ and CIN3+ lesions with histology as the reference standard
measure: Acceptability and feasibility
time frame: Day 0 and Week 1
description: Acceptability and feasibility of the self-sampling, of the different triage options and of the treatment cervical lesions
measure: Prevalence of CIN2+ lesions
time frame: Day 0
description: Prevalence of CIN2 lesions, overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history
measure: Prevalence of CIN3+ lesions
time frame: Day 0
description: Prevalence of CIN3 lesions overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history
measure: Prevalence of cervical cancer
time frame: Day 0
description: Prevalence of cervical cancer overall and by sub-groups defined by age categories, current CD4-cell count, nadir CD4-cell count and treatment history
measure: Adverse events
time frame: Day 0 and Week 1 up to 24 weeks
description: Rate and nature of adverse events and protocol violations
measure: Proportion of the women eligible to HPV screening who were actually screened and treated (if required)
time frame: Day 0
description: Proportion of the women eligible for the study who were actually screened, treated (if required)
measure: Evaluation of the micro-costing
time frame: Day 0 up to Week 26
description: Evaluation of the micro-costing of the various components of the screening strategies
measure: Evaluation of post-treatment HPV clearance
time frame: Week 24 and 48 post treatment
description: Evaluation of the HPV clearance at M6 and M12 after thermal-ablation
measure: Evaluation of post-treatment cervical lesion
time frame: Week 48 post treatment
description: Evaluation of the proportion of CIN2 and CIN3 at M12 after treatment
arm group label: Triage with different options
arm group type: Other
description: All women will have an HPV test, partial genotyping (16/18/45 versus other high-risk HPV [hr-HPV]) and VIA. The different options for triage that will be compared are:
Participants hr-HVP+ and VIA+ participants selected for treatment;
Participants HPV 16/18/45+ selected for treatment;
Participant HPV 16/18/45+ and/or VIA+ selected for treatment;
intervention type: Diagnostic Test
intervention name: HPV test with partial genotyping and VIA triage
description: HPV testing with the GenXpert platform VIA Biopsies of VIA+ lesions or random Treatment with thermal ablation of women with precancerous lesions
arm group label: Triage with different options
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 49 Years
healthy volunteers: No
last name: Pierre Debeaudrap, PhD
role: Study Director
affiliation: CEPED - UMR196
last name: Apollinaire Debeaudrap, PhD
role: Study Director
affiliation: PACCI - Ivory Coast
last name: Pierre Debeaudrap, PhD
phone: (0) 1 76 53 34 53
phone ext: +33
email: pierre.debeaudrap@ird.fr
last name: Apollinaire Horo, PhD
email: horoapollinaire@gmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Enrolling by invitation
country: Burkina Faso
country: Cambodia
country: Côte D'Ivoire
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: HIV Infections
mesh term: Papillomavirus Infections
mesh term: Uterine Cervical Neoplasms
mesh term: Papilloma
sharing ipd: No