<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/NCT03033017</url>
  </required_header>
  <id_info>
    <org_study_id>24777</org_study_id>
    <nct_id>NCT03033017</nct_id>
  </id_info>
  <brief_title>Predictors of Time to Viremia With an Analytic Treatment Interruption</brief_title>
  <official_title>Predictors of Time to Viremia With an Analytic Treatment Interruption</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a two-center study of 30 HIV-infected participants who have been on antiretroviral&#xD;
      therapy (ART) for at least two years.&#xD;
&#xD;
      Participants will be asked to undergo LN and GALT biopsies both before and after a closely&#xD;
      monitored analytic treatment interruption (ATI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The HIV field has made a dramatic shift to an emphasis on finding a cure for HIV.&#xD;
&#xD;
      However, there is no agreed upon test of cure, or even what the definition of a cure might&#xD;
      be. The investigator believes the most reliable test of cure will be an analytic treatment&#xD;
      interruption (ATI) with time to viremia as a standard measure of the impact of an&#xD;
      intervention on the degree to which the reservoir has been depleted. This is rational as&#xD;
      modeling studies utilizing ATI data point to reservoir size as an important predictor of time&#xD;
      to viremia(1) and other studies have shown that levels of HIV DNA(2) and cell associated HIV&#xD;
      RNA(3) prior to starting antiretroviral therapy (ART) are associated with time-to-rebound.&#xD;
      However, these studies used a limited sampling strategy to determine when viremia rebounded&#xD;
      and it is likely that greater sensitivity in measures of time-to rebound will be needed to&#xD;
      accurately assess the impact of an intervention. The investigators have tested an ATI&#xD;
      strategy where plasma HIV is sampled three times each week and ART is resumed once the virus&#xD;
      becomes detectable. In this small, pilot study, the investigators sampled lymph nodes, GALT,&#xD;
      plasma, and PBMC before, during, and after the ATI and found the time-to-rebound was 14 days&#xD;
      (range 5 to 30 days) and that total years of ART exposure was associated with the&#xD;
      time-to-rebound (4). The investigators propose a similar study that includes more intensive&#xD;
      blood and lymphoid tissue sampling to identify factors that predict time to-rebound to&#xD;
      provide a necessary foundation for future studies that utilize a treatment interruption as a&#xD;
      test of efficacy for curative interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Funding c hange&#xD;
  </why_stopped>
  <start_date>July 2016</start_date>
  <completion_date type="Anticipated">January 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2019</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>Time to viremia</measure>
    <time_frame>Baseline to 14 days</time_frame>
    <description>Time to viremia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in vRNA+ and vDNA+ cells</measure>
    <time_frame>Baseline to 14 days</time_frame>
    <description>measured by in situ hybridization and using quantitative image analysis to determine the frequency of + cell/gram lymphoid tissue</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SCA (Single Copy Assay)</measure>
    <time_frame>Baseline to 14 days</time_frame>
    <description>performed as described in the protocol and reported as number of cells/ml plasma.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in markers of immune activation</measure>
    <time_frame>Baseline to 14 days</time_frame>
    <description>All measurements are the same IL1B, TNF, IL4, IL13, IL17, IL21,IL22, IL6, IL10</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CD4</measure>
    <time_frame>Baseline to 14 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CD4/CD8 ratio</measure>
    <time_frame>Baseline to 14 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Polyadenylation-RT-ddPCR assay for total transcripts (TAR)</measure>
    <time_frame>Baseline to 14 days</time_frame>
    <description>transcripts/million cells</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ddPCR assays for read-through, elongated, polyadenylated, and multiply-spliced (Tat-Rev) transcripts</measure>
    <time_frame>Baseline to 14 days</time_frame>
    <description>reported as transcripts/million cells</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>HIV-infected on antiretroviral therapy 2 years</arm_group_label>
    <description>HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood Testing</intervention_name>
    <arm_group_label>HIV-infected on antiretroviral therapy 2 years</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Lymph node biopsy: Inguinal lymph node biopsies will be collected per institutional&#xD;
      guidelines&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two&#xD;
        years.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HIV-infected individuals who have been on ART therapy for at least two years&#xD;
&#xD;
          2. Male or Female, aged 18 years or older&#xD;
&#xD;
          3. Documented evidence of CD4+ T cell count ≥ 300 cells/µl for 12 months prior to study&#xD;
             entry&#xD;
&#xD;
          4. BMI ≤ 30 or evidence by ultrasound or physical exam of peripheral inguinal lymph&#xD;
             node(s) that is/are surgically accessible&#xD;
&#xD;
          5. Documented plasma HIV RNA levels below level of quantification &lt;20 to &lt;40 copies&#xD;
             RNA/mL depending on the assay) ≥ 24 months (a single measurement above the level of&#xD;
             detection but &lt; 200 copies/ml will be allowed)&#xD;
&#xD;
          6. Willing to switch to an ART regimen consisting of dolutegravir and either&#xD;
             tenofovir/emtricitabine or abacavir/lamivudine to avoid drugs with a long-half life&#xD;
             that would expose the participant to a period of mono-therapy when the drugs are&#xD;
             stopped.&#xD;
&#xD;
          7. Women of child bearing potential and men with partners of child bearing potential must&#xD;
             agree to use effective contraception during protocol&#xD;
&#xD;
          8. Able to provide voluntary written consent.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. ART was initiated during acute infection (within first 6 months of infection)&#xD;
&#xD;
          2. Planning or current pregnancy or breastfeeding&#xD;
&#xD;
          3. History and/or presence of any clinically significant disease or disorder, such as&#xD;
             cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and&#xD;
             psychiatric/mental disease/disorder, which, in the opinion of the enrolling physician,&#xD;
             may put the participant at risk because of participation in the study, influence the&#xD;
             results of the study, or affect the participant's ability to participate in the study.&#xD;
&#xD;
          4. Inability to comply with study procedures per enrolling physician discretion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Timothy Schacker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>October 7, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>December 1, 2017</last_update_submitted>
  <last_update_submitted_qc>December 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Viremia</mesh_term>
  </condition_browse>
  <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/NCT03033017
org study id: 24777
nct id: NCT03033017
lead sponsor: 
has dmc: No
This is a two-center study of 30 HIV-infected participants who have been on antiretroviral
      therapy (ART) for at least two years.

      Participants will be asked to undergo LN and GALT biopsies both before and after a closely
      monitored analytic treatment interruption (ATI).
The HIV field has made a dramatic shift to an emphasis on finding a cure for HIV.

      However, there is no agreed upon test of cure, or even what the definition of a cure might
      be. The investigator believes the most reliable test of cure will be an analytic treatment
      interruption (ATI) with time to viremia as a standard measure of the impact of an
      intervention on the degree to which the reservoir has been depleted. This is rational as
      modeling studies utilizing ATI data point to reservoir size as an important predictor of time
      to viremia(1) and other studies have shown that levels of HIV DNA(2) and cell associated HIV
      RNA(3) prior to starting antiretroviral therapy (ART) are associated with time-to-rebound.
      However, these studies used a limited sampling strategy to determine when viremia rebounded
      and it is likely that greater sensitivity in measures of time-to rebound will be needed to
      accurately assess the impact of an intervention. The investigators have tested an ATI
      strategy where plasma HIV is sampled three times each week and ART is resumed once the virus
      becomes detectable. In this small, pilot study, the investigators sampled lymph nodes, GALT,
      plasma, and PBMC before, during, and after the ATI and found the time-to-rebound was 14 days
      (range 5 to 30 days) and that total years of ART exposure was associated with the
      time-to-rebound (4). The investigators propose a similar study that includes more intensive
      blood and lymphoid tissue sampling to identify factors that predict time to-rebound to
      provide a necessary foundation for future studies that utilize a treatment interruption as a
      test of efficacy for curative interventions.
observational model: Cohort
time perspective: Prospective
measure: Time to viremia
time frame: Baseline to 14 days
description: Time to viremia
measure: Change in vRNA+ and vDNA+ cells
time frame: Baseline to 14 days
description: measured by in situ hybridization and using quantitative image analysis to determine the frequency of + cell/gram lymphoid tissue
measure: SCA (Single Copy Assay)
time frame: Baseline to 14 days
description: performed as described in the protocol and reported as number of cells/ml plasma.
measure: Change in markers of immune activation
time frame: Baseline to 14 days
description: All measurements are the same IL1B, TNF, IL4, IL13, IL17, IL21,IL22, IL6, IL10
measure: Change in CD4
time frame: Baseline to 14 days
measure: Change in CD4/CD8 ratio
time frame: Baseline to 14 days
measure: Polyadenylation-RT-ddPCR assay for total transcripts (TAR)
time frame: Baseline to 14 days
description: transcripts/million cells
measure: ddPCR assays for read-through, elongated, polyadenylated, and multiply-spliced (Tat-Rev) transcripts
time frame: Baseline to 14 days
description: reported as transcripts/million cells
arm group label: HIV-infected on antiretroviral therapy 2 years
description: HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
intervention type: Other
intervention name: Blood Testing
arm group label: HIV-infected on antiretroviral therapy 2 years
Lymph node biopsy: Inguinal lymph node biopsies will be collected per institutional
      guidelines
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Timothy Schacker, MD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Viremia
sharing ipd: Undecided