<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/NCT03001128</url>
  </required_header>
  <id_info>
    <org_study_id>ACTG A5345</org_study_id>
    <secondary_id>UM1AI068636</secondary_id>
    <nct_id>NCT03001128</nct_id>
  </id_info>
  <brief_title>Biomarkers to Predict Time to Plasma HIV RNA Rebound</brief_title>
  <official_title>Identification of Biomarkers to Predict Time to Plasma HIV RNA Rebound and Post-Treatment Viral Control During an Intensively Monitored Antiretroviral Pause (IMAP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AIDS Clinical Trials Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>AIDS Clinical Trials Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to collect information about what happens when people pause, or&#xD;
      temporarily stop taking, ART, and to collect blood samples from these people at frequent&#xD;
      intervals. We will also study the safety of pausing ART under close observation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 23, 2017</start_date>
  <completion_date type="Actual">January 29, 2021</completion_date>
  <primary_completion_date type="Actual">January 29, 2021</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 from ART discontinuation to HIV RNA rebound</measure>
    <time_frame>Up to 96 weeks following ART discontinuation</time_frame>
    <description>Time from ART discontinuation (start of MAP) to HIV RNA rebound to ≥ 1,000 copies/mL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of sustained post-treatment HIV control</measure>
    <time_frame>≥24 weeks off ART without meeting ART re-initiation criteria</time_frame>
    <description>Frequency of sustained post-treatment HIV control in participants treated during early and chronic infection undergoing an IMAP</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Association between pre-IMAP CA-RNA and time to HIV rebound</measure>
    <time_frame>Up to 96 weeks following ART discontinuation</time_frame>
    <description>Association between pre-IMAP CA-RNA and time to HIV rebound</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">61</enrollment>
  <condition>HIV-1 Infection</condition>
  <arm_group>
    <arm_group_label>Cohort A: ART initiated during chronic infection</arm_group_label>
    <description>Cohort A will include 36 participants who initiated ART during chronic infection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B: ART initiated during acute or early infection</arm_group_label>
    <description>Cohort B will include 30 participants who initiated ART during acute/early HIV infection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antiretroviral treatment pause</intervention_name>
    <description>Antiretroviral treatment pause</description>
    <arm_group_label>Cohort A: ART initiated during chronic infection</arm_group_label>
    <arm_group_label>Cohort B: ART initiated during acute or early infection</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        HIV-infected men and women ≥18 to ≤70 years of age, maintained on suppressive ART for a&#xD;
        minimum of 2 years with CD4+ count ≥500 cells/mm3 and nadir CD4+ count ≥200 cells/mm3.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Step 1 Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or&#xD;
             chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and&#xD;
             confirmed by a licensed Western blot or a second antibody test by a method other than&#xD;
             the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.&#xD;
&#xD;
        NOTE: The term &quot;licensed&quot; refers to a US FDA-approved kit, which is required for all IND&#xD;
        studies, or for sites located in countries other than the United States, a kit that has&#xD;
        been certified or licensed by an oversight body within that country and validated&#xD;
        internally.&#xD;
&#xD;
          -  Plasma HIV-1 RNA &gt;1000 copies/mL by any assay obtained prior to initiating ART. NOTE:&#xD;
             Documentation or candidate recall is acceptable.&#xD;
&#xD;
          -  For Cohort A participants, ART initiated during chronic infection (e.g., more than 6&#xD;
             months after estimated date of infection, or as determined by site investigator, study&#xD;
             team, or available medical records).&#xD;
&#xD;
          -  For Cohort B, diagnosis of acute HIV infection (AHI) as defined by the criteria listed&#xD;
             below.&#xD;
&#xD;
        Fiebig Staging Criteria (must be source documented):&#xD;
&#xD;
          -  Fiebig I-II: E/CIA negative, HIV-1 RNA or p24 antigen positive, and negative or&#xD;
             indeterminate Western blot, if performed&#xD;
&#xD;
          -  Fiebig III-IV: Reactive HIV-1 antibody and negative or indeterminate results on the&#xD;
             Western blot or Geenius HIV-1/HIV-2&#xD;
&#xD;
          -  Fiebig V: Reactive HIV-1 antibody and positive Western blot or Geenius HIV-1/HIV-2&#xD;
             without p31 band NOTE A: ART must have been initiated more than 10 days after Fiebig&#xD;
             I-II diagnosis and less than 90 days after Fiebig V diagnosis to qualify for Cohort B.&#xD;
             NOTE B: Candidates who were diagnosed with Fiebig I-II AHI must have had a positive&#xD;
             HIV-1 RNA test or subsequently have had a positive Western blot if no positive HIV-1&#xD;
             RNA test was available.&#xD;
&#xD;
               -  Receiving continuous ART for at least 2 years and on any NNRTI-, PI-, or&#xD;
                  INSTI-containing regimen.&#xD;
&#xD;
        NOTE A: ART interruptions of up to 7 days and at least 90 days prior to entry are&#xD;
        acceptable.&#xD;
&#xD;
        NOTE B: Within- and between-class changes in ART within the previous 2 years are&#xD;
        acceptable.&#xD;
&#xD;
          -  For candidates whose ART includes an NNRTI, willingness and ability to change to a PI-&#xD;
             or INSTI-containing regimen for at least 4 weeks prior to ART interruption and the&#xD;
             local availability of such a regimen.&#xD;
&#xD;
          -  Nadir CD4+ cell count ≥200 cells/mm3.&#xD;
&#xD;
        NOTE: Candidate recall or documentation is acceptable.&#xD;
&#xD;
          -  CD4+ cell count ≥500 cells/mm3 obtained within 90 days prior to study entry in a US&#xD;
             laboratory that has is compliant with Clinical Laboratory Improvement Amendments&#xD;
             (CLIA) or its equivalent or in any network approved non-US laboratory that operates in&#xD;
             accordance with Good Clinical Laboratory Practices (GCLP) and participates in&#xD;
             appropriate external quality assurance (EQA) programs.&#xD;
&#xD;
          -  One documented plasma HIV-1 RNA that is below the limit of detection of an&#xD;
             FDA-approved assays (limit of detection: 75, 50, 40, or 20 copies/mL) between 12 and&#xD;
             24 months prior to the screening HIV-1 RNA and one documented HIV-1 RNA that is below&#xD;
             the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40, or&#xD;
             20 copies/mL) collected fewer than 12 months prior to the screening HIV-1 RNA.&#xD;
&#xD;
          -  Plasma HIV-1 RNA level below the limit of assay quantification within 90 days prior to&#xD;
             entry.&#xD;
&#xD;
          -  The following laboratory values obtained within 90 days prior to entry by any US&#xD;
             laboratory that is compliant with CLIA or its equivalent or in any network approved&#xD;
             non-US laboratory that operates in accordance with GCLP and participates in&#xD;
             appropriate EQA programs.&#xD;
&#xD;
        Absolute neutrophil count (ANC) ≥750 cells/mm3 Hemoglobin ≥11.0 g/dL for men and ≥10.0 g/dL&#xD;
        for women Platelet count ≥100,000/mm3 Creatinine ≤1.5 mg/dL Aspartate aminotransferase&#xD;
        (AST) (SGOT) ≤1.5x upper limit of normal (ULN) Alanine aminotransferase (ALT) (SGPT) ≤1.5x&#xD;
        ULN&#xD;
&#xD;
          -  HCV antibody negative result obtained within 90 days prior to study entry or, if the&#xD;
             HCV antibody result is positive, a negative HCV RNA result within 90 days prior to&#xD;
             study entry and no positive HCV RNA result within 24 weeks prior to entry.&#xD;
&#xD;
          -  Ability and willingness of participant to provide informed consent.&#xD;
&#xD;
          -  Willingness to have blood samples collected and stored indefinitely and used for&#xD;
             HIV-related research purposes.&#xD;
&#xD;
          -  For females of reproductive potential (women who have not been post-menopausal for at&#xD;
             least 24 consecutive months, i.e., who have had menses within the preceding 24 months,&#xD;
             or women who have not undergone surgical sterilization, specifically hysterectomy, or&#xD;
             bilateral oophorectomy and/or bilateral salpingectomy), a negative serum or urine&#xD;
             pregnancy test within 48 hours prior to study entry by any clinic or laboratory that&#xD;
             has a CLIA certification or its equivalent, or is using a point of care CLIA-waived&#xD;
             test, or at any network approved non-US laboratory or clinic that operates in&#xD;
             accordance with Good Clinical Laboratory Practices and participates in appropriate&#xD;
             external quality assurance programs.&#xD;
&#xD;
        NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral&#xD;
        salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is&#xD;
        participant-reported history.&#xD;
&#xD;
          -  All participants must agree to use barrier protection (e.g., condoms, dental dams) for&#xD;
             all sexual activity throughout the entire course of the study to prevent HIV&#xD;
             transmission.&#xD;
&#xD;
          -  All participants must agree not to participate in the conception process (e.g., active&#xD;
             attempt to become pregnant or to impregnate, sperm donation, or in vitro&#xD;
             fertilization). If participating in sexual activity that could lead to pregnancy, the&#xD;
             participant/partner must use at least two reliable forms of contraceptives (e.g.,&#xD;
             condoms, with or without a spermicidal agent; a diaphragm or cervical cap with&#xD;
             spermicide; an IUD; hormone-based contraception), with at least one being a barrier&#xD;
             method, during the study.&#xD;
&#xD;
          -  Site investigator anticipates that a fully active alternative ART regimen could be&#xD;
             constructed and would be available in the event of virologic failure on the&#xD;
             participant's current ART regimen.&#xD;
&#xD;
          -  Absence of either active hepatitis B virus (HBV) infection, indicated by a negative&#xD;
             hepatitis B surface antigen (HBsAg) or HBV viral load assays within 90 days prior to&#xD;
             entry or known chronic hepatitis B infection based on a previously positive HBV DNA or&#xD;
             positive HBsAg without a subsequent positive hepatitis B surface antibody (HBsAb).&#xD;
&#xD;
        Step 1 Exclusion Criteria:&#xD;
&#xD;
          -  Any plasma HIV-1 RNA at or above the limit of detection of the FDA-approved assays&#xD;
             (limit of detection: 75, 50, 40, or 20 copies/mL) within 24 months prior to entry.&#xD;
&#xD;
        NOTE: A single unconfirmed &quot;blip&quot; (i.e., plasma HIV-1 RNA over limit of detection but &lt;200&#xD;
        copies/mL) is allowed if preceded and followed by values below the limit of detection and&#xD;
        if the blip occurred more than 6 months prior to study entry.&#xD;
&#xD;
          -  Currently breastfeeding or plans on breastfeeding during the course of the study or is&#xD;
             pregnant.&#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;
          -  Any history of an AIDS-defining illness using the current list on the U.S. Centers for&#xD;
             Disease Control and Prevention (CDC)'s website.&#xD;
&#xD;
          -  Receipt of any study-defined prohibited medications within 6 months prior to entry.&#xD;
&#xD;
          -  Prior history of difficulty establishing venous access or current contraindication for&#xD;
             leukapheresis, in the opinion of the site investigator and based on assessments.&#xD;
&#xD;
          -  Receipt of any vaccination within 1 week prior to entry.&#xD;
&#xD;
        NOTE: The entry visit must be scheduled to ensure that 1 week has elapsed after any&#xD;
        vaccination.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan Li, MD, MMS</last_name>
    <role>Study Chair</role>
    <affiliation>Brigham and Women's Hospital ACTG CRS</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Smith, MD, MAS</last_name>
    <role>Study Chair</role>
    <affiliation>University of California San Diego AVRC CRS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>601 University of California, Los Angeles CARE Center CRS</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>701 University of California, San Diego AntiViral Research Center CRS</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>801 University of California, San Francisco HIV/AIDS CRS</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital CRS (6101)</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Whitman Walker Health CRS (31791)</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>2701 Northwestern University CRS</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush Univ. Med. Ctr. ACTG CRS (2702)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>101 Massachusetts General Hospital (MGH) CRS</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>107 Brigham and Women's Hosp. ACTG CRS</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington U CRS (2101)</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>3201 Chapel Hill CRS</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>3203 Greensboro CRS</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pittsburgh CRS (1001)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>3652 Vanderbilt Therapeutics (VT) CRS</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>31443 Trinity Health and Wellness Center CRS</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>5401 Puerto Rico AIDS Clinical Trials Unit CRS</name>
      <address>
        <city>San Juan</city>
        <zip>00931</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS</name>
      <address>
        <city>Bangkok</city>
        <state>Patumwan</state>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>July 31, 2021</last_update_submitted>
  <last_update_submitted_qc>July 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Retroviral Agents</mesh_term>
  </intervention_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/NCT03001128
org study id: ACTG A5345
secondary id: UM1AI068636
nct id: NCT03001128
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to collect information about what happens when people pause, or
      temporarily stop taking, ART, and to collect blood samples from these people at frequent
      intervals. We will also study the safety of pausing ART under close observation.
observational model: Cohort
time perspective: Prospective
measure: Time from ART discontinuation to HIV RNA rebound
time frame: Up to 96 weeks following ART discontinuation
description: Time from ART discontinuation (start of MAP) to HIV RNA rebound to ≥ 1,000 copies/mL
measure: Frequency of sustained post-treatment HIV control
time frame: ≥24 weeks off ART without meeting ART re-initiation criteria
description: Frequency of sustained post-treatment HIV control in participants treated during early and chronic infection undergoing an IMAP
measure: Association between pre-IMAP CA-RNA and time to HIV rebound
time frame: Up to 96 weeks following ART discontinuation
description: Association between pre-IMAP CA-RNA and time to HIV rebound
arm group label: Cohort A: ART initiated during chronic infection
description: Cohort A will include 36 participants who initiated ART during chronic infection.
arm group label: Cohort B: ART initiated during acute or early infection
description: Cohort B will include 30 participants who initiated ART during acute/early HIV infection.
intervention type: Drug
intervention name: Antiretroviral treatment pause
description: Antiretroviral treatment pause
arm group label: Cohort A: ART initiated during chronic infection
arm group label: Cohort B: ART initiated during acute or early infection
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jonathan Li, MD, MMS
role: Study Chair
affiliation: Brigham and Women's Hospital ACTG CRS
last name: David Smith, MD, MAS
role: Study Chair
affiliation: University of California San Diego AVRC CRS
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Puerto Rico
country: Thailand
country: United States
responsible party type: Sponsor
mesh term: Anti-Retroviral Agents
sharing ipd: Undecided