xml: <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/NCT06016114</url>
    </required_header>
    <id_info>
      <org_study_id>ARCH</org_study_id>
      <nct_id>NCT06016114</nct_id>
    </id_info>
    <brief_title>Analysis of the Reservoir in Individuals Controlling HIV Infection</brief_title>
    <acronym>ARCH</acronym>
    <official_title>Analysis of the Reservoir in Individuals Controlling HIV Infection</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Ghent</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Ghent</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this study is the gain new insights into HIV latency in HIV controllers through&#xD;
        extensive blood an tissue sampling (lymph node, colon biopsies, placenta) from 25 individuals&#xD;
        living with HIV and healthy individuals.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2028</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Quantification of total and intact HIV DNA and HIV RNA</measure>
      <time_frame>5 years</time_frame>
      <description>Rainbow assay: multiplex digital PCR approach that combines five different HIV-1 regions to quantify total HIV-1 DNA and intact HIV-1 DNA simultaneously (Qiacuity dPCR platform, Qiagen).&#xD;
  mutliplex digital PCR approach to quantify HIV RNA</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Integration site analysis</measure>
      <time_frame>5 years</time_frame>
      <description>HIV/host DNA junctions will be amplified using the Integration Site Loop Amplification (ISLA) assay, and resulting chimeric amplicons will be sequenced by Sanger.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Full-length HIV genome analysis</measure>
      <time_frame>5 years</time_frame>
      <description>Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Epigenetic analysis</measure>
      <time_frame>5 years</time_frame>
      <description>Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Matched integration site and proviral sequencing</measure>
      <time_frame>5 years</time_frame>
      <description>MIP-seq: captures full-length viral genome sequences in conjunction with its associated viral integration site</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Proviral UMI-mediated Long-read Sequencing</measure>
      <time_frame>5 years</time_frame>
      <description>HIV-PULSE: characterize the composition of the viral reservoir using long-read sequencing. Involves pre-amplifying individual proviral genomes using PCR and tagging them with dual UMIs, followed by long-range PCR amplification and long-read sequencing on the Oxford Nanopore MinION platform</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Transcriptome analysis</measure>
      <time_frame>5 years</time_frame>
      <description>Bulk RNA sequencing on extracted RNA (Illumina Hiseq 2500 with 10-100 ng input of ribodepleted RNA)&#xD;
  Single cell RNA sequencing (10x genomics technology )</description>
    </primary_outcome>
    <primary_outcome>
      <measure>High dimensional phenotyping</measure>
      <time_frame>5 years</time_frame>
      <description>CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunohistochemistry, RNA- and DNA In Situ Hybridization</measure>
      <time_frame>5 years</time_frame>
      <description>Immunochemistry will be used to study the expression of activation and exhaustion markers on tissues samples , while viral expression will be assessed through DNAScope and RNAScope technologies</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunometabolic profile analysis</measure>
      <time_frame>5 years</time_frame>
      <description>Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Detection of translation-competent reservoirs</measure>
      <time_frame>5 years</time_frame>
      <description>HIV-Flow assay: flow cytometry based assay using a combination of 2 antibodies targeting the p24 protein and allowing the detection of cells containing translation-competent viruses. p24+ cells detected by this assay can be sorted for downstream applications and further characterization of translation-competent reservoirs.&#xD;
  The Simultaneous TCR Integration site and Provirus sequencing (STIP-seq) assay will be performed to sequence the proviral genome and matched integration sites of the translation-competent viruses, as well as phenotypic characterization and TCR sequencing of the host cell. characterization of translation-competent reservoirs.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunological analysis-FACS</measure>
      <time_frame>5 years</time_frame>
      <description>Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using FACS analysis.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunological analysis-ELISA</measure>
      <time_frame>5 years</time_frame>
      <description>Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using ELISA.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Microbiome monitoring</measure>
      <time_frame>5 years</time_frame>
      <description>Gut microbiome will be analyzed in stool and colon biopsies using next-generation sequencing (NGS) of rRNA gene amplicons to identify bacteria at genus/species level</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Hiv</condition>
    <arm_group>
      <arm_group_label>HIV-1 positive individuals (non-pregnant)</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Pregnant HIV-1 positive/negative individuals</arm_group_label>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          HIV-positive individuals (pregnant and non-pregnant) and pregnant HIV-negative individuals&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Elite Controllers: pVL&lt;50 copies per ml for at least 12 months, treatment naive at the&#xD;
               time of inclusion&#xD;
  &#xD;
            -  Viral controllers: pVL &lt;2000 copies/ml; CD4&gt;500/µL for at least two years, treatment&#xD;
               naïve at the time of inclusion&#xD;
  &#xD;
            -  Long-term non-progressors: CD4&gt;500/µL, pVL &lt;10000 copies/ml, for at least 7 years,&#xD;
               treatment naïve at the time of inclusion&#xD;
  &#xD;
            -  Post treatment controllers: on cART for at least 12 months; pVL &lt;500 copies/ml for at&#xD;
               least 2 years after treatment cessation .&#xD;
  &#xD;
            -  PLWH who received bone marrow transplant: people living with HIV who received a&#xD;
               bone-marrow transplant for non-HIV related reasons&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current history of opportunistic infection (AIDS defining events as defined in&#xD;
               category C of the CDC clinical classification), consisting of chronic HIV-1 infection.&#xD;
  &#xD;
            -  Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral&#xD;
               load positive in the past and no evidence of subsequent seroconversion (= HBV antigen&#xD;
               or viral load negative and positive HBV surface antibody)).&#xD;
  &#xD;
            -  Evidence of active HCV infection (HCV antibody positive result within 60 days prior to&#xD;
               study entry with positive HCV viral load or, if the HCV antibody result is negative, a&#xD;
               positive HCV RNA result within 60 days prior to study entry).&#xD;
  &#xD;
            -  Current or known history of cardiomyopathy or significant ischemic or cerebrovascular&#xD;
               disease.&#xD;
  &#xD;
            -  Current history of cancer.&#xD;
  &#xD;
            -  History of HIV-related thrombocytopenia.&#xD;
  &#xD;
            -  Any condition, including preexisting psychiatric and psychological disorders, which&#xD;
               will in the opinion of the investigator interfere with the trial conduct or safety of&#xD;
               the participant.&#xD;
  &#xD;
            -  Abnormal results of standard of care laboratory tests:&#xD;
  &#xD;
                 1. Confirmed haemoglobin &lt;11g/dl for women and &lt;12 g/dl for men&#xD;
  &#xD;
                 2. Confirmed platelet count &lt;100 000/µl *&#xD;
  &#xD;
                 3. Confirmed neutrophil count &lt;1000/μl&#xD;
  &#xD;
                 4. Confirmed AST and/or ALT &gt;10xULN&#xD;
  &#xD;
            -  Active drug or alcohol use or dependence that, in the opinion of the site&#xD;
               investigator, would interfere with adherence to study requirements.&#xD;
  &#xD;
            -  Acute or serious illness, in the opinion of the site investigator, requiring systemic&#xD;
               treatment and/or hospitalization within 60 days prior to entry.&#xD;
  &#xD;
            -  The following treatment will be prohibited three months before screening and during&#xD;
               the study:&#xD;
  &#xD;
                 1. immunosuppressive drugs (inclusive corticosteroids) except for drugs used for&#xD;
                    topical use.&#xD;
  &#xD;
                 2. Immunomodulatory drugs including but not limited to Granulocyte-colony&#xD;
                    stimulating factors, Granulocyte-monocyte colony-stimulating factor, interleukin&#xD;
                    2, 7 &amp; 15.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Linos Vandekerckhove, MD PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospital, Ghent</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Klara Dewitte</last_name>
      <phone>+32 9 332 06 98</phone>
      <email>klara.dewitte@ugent.be</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HIV</keyword>
    <keyword>Latency</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>
  
  
text: 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/NCT06016114
  org study id: ARCH
  nct id: NCT06016114
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The aim of this study is the gain new insights into HIV latency in HIV controllers through
        extensive blood an tissue sampling (lymph node, colon biopsies, placenta) from 25 individuals
        living with HIV and healthy individuals.
  observational model: Cohort
  time perspective: Prospective
  measure: Quantification of total and intact HIV DNA and HIV RNA
  time frame: 5 years
  description: Rainbow assay: multiplex digital PCR approach that combines five different HIV-1 regions to quantify total HIV-1 DNA and intact HIV-1 DNA simultaneously (Qiacuity dPCR platform, Qiagen).
  mutliplex digital PCR approach to quantify HIV RNA
  measure: Integration site analysis
  time frame: 5 years
  description: HIV/host DNA junctions will be amplified using the Integration Site Loop Amplification (ISLA) assay, and resulting chimeric amplicons will be sequenced by Sanger.
  measure: Full-length HIV genome analysis
  time frame: 5 years
  description: Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.
  measure: Epigenetic analysis
  time frame: 5 years
  description: Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)
  measure: Matched integration site and proviral sequencing
  time frame: 5 years
  description: MIP-seq: captures full-length viral genome sequences in conjunction with its associated viral integration site
  measure: Proviral UMI-mediated Long-read Sequencing
  time frame: 5 years
  description: HIV-PULSE: characterize the composition of the viral reservoir using long-read sequencing. Involves pre-amplifying individual proviral genomes using PCR and tagging them with dual UMIs, followed by long-range PCR amplification and long-read sequencing on the Oxford Nanopore MinION platform
  measure: Transcriptome analysis
  time frame: 5 years
  description: Bulk RNA sequencing on extracted RNA (Illumina Hiseq 2500 with 10-100 ng input of ribodepleted RNA)
  Single cell RNA sequencing (10x genomics technology )
  measure: High dimensional phenotyping
  time frame: 5 years
  description: CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells
  measure: Immunohistochemistry, RNA- and DNA In Situ Hybridization
  time frame: 5 years
  description: Immunochemistry will be used to study the expression of activation and exhaustion markers on tissues samples , while viral expression will be assessed through DNAScope and RNAScope technologies
  measure: Immunometabolic profile analysis
  time frame: 5 years
  description: Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells
  measure: Detection of translation-competent reservoirs
  time frame: 5 years
  description: HIV-Flow assay: flow cytometry based assay using a combination of 2 antibodies targeting the p24 protein and allowing the detection of cells containing translation-competent viruses. p24+ cells detected by this assay can be sorted for downstream applications and further characterization of translation-competent reservoirs.
  The Simultaneous TCR Integration site and Provirus sequencing (STIP-seq) assay will be performed to sequence the proviral genome and matched integration sites of the translation-competent viruses, as well as phenotypic characterization and TCR sequencing of the host cell. characterization of translation-competent reservoirs.
  measure: Immunological analysis-FACS
  time frame: 5 years
  description: Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using FACS analysis.
  measure: Immunological analysis-ELISA
  time frame: 5 years
  description: Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using ELISA.
  measure: Microbiome monitoring
  time frame: 5 years
  description: Gut microbiome will be analyzed in stool and colon biopsies using next-generation sequencing (NGS) of rRNA gene amplicons to identify bacteria at genus/species level
  arm group label: HIV-1 positive individuals (non-pregnant)
  arm group label: Pregnant HIV-1 positive/negative individuals
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  last name: Linos Vandekerckhove, MD PhD
  role: Principal Investigator
  affiliation: University Hospital, Ghent
  last name: Klara Dewitte
  phone: +32 9 332 06 98
  email: klara.dewitte@ugent.be
  responsible party type: Sponsor
  mesh term: HIV Infections