<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/NCT03292432</url>
  </required_header>
  <id_info>
    <org_study_id>ATN 152</org_study_id>
    <secondary_id>5U24HD089880-02</secondary_id>
    <nct_id>NCT03292432</nct_id>
  </id_info>
  <brief_title>Triggered Escalating Real-time Adherence (TERA) Intervention</brief_title>
  <acronym>TERA</acronym>
  <official_title>Triggered Escalating Real-time Adherence Intervention to Promote Rapid HIV Viral Suppression Among Youth Living With HIV Failing Antiretroviral Therapy: The TERA Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Minority Health and Health Disparities (NIMHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Youth Living with HIV (YLWH) often face unique challenges achieving high and sustained rates&#xD;
      of adherence to their antiretroviral therapy (ART). Poor adherence can lead to unsuppressed&#xD;
      virus, more advanced HIV disease and poorer health outcomes, eventually exhausting treatment&#xD;
      options. To date however, there are few demonstrated interventions for youth failing first&#xD;
      line therapy. This study evaluated a novel intervention that used remote coaching through&#xD;
      video enabled counseling sessions, an Electronic Dose Monitoring (EDM) pill bottle that&#xD;
      notified an adherence coach when youth failed to open/close the device around dose time, and&#xD;
      problem solving outreach by the coach in response to not dosing from the EDM. This intensive&#xD;
      'boot camp' strategy was implemented for 12 weeks followed by observation through 48 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a Phase II, two-arm, randomized, open-label study. Eligible participants had failed&#xD;
      ART therapy, defined as having a detectable plasma Human Immunodeficiency Virus - Type 1&#xD;
      Ribonucleic Acid (HIV-1 RNA) ≥200 copies/ml within 45 days of enrollment despite having been&#xD;
      prescribed ART for at least 24 weeks. They could continue the same ART regimen or start a new&#xD;
      once daily regimen. Participants were stratified by age (&lt;18 vs. ≥18 years of age) and&#xD;
      randomized in equal proportions to receive the study intervention (TERA) or standard of care&#xD;
      (SOC), with no enrollment limits in each stratum. Target accrual was 120 participants to be&#xD;
      enrolled over one year.&#xD;
&#xD;
      TERA was a time-limited (12 weeks) intervention approach that (a) used wireless electronic&#xD;
      dose monitoring (EDM) to identify dose-times passing with no bottle opening, (b) sent a text&#xD;
      asking about the delay, (c) evaluated response to the text and (d) initiated follow-up by an&#xD;
      adherence coach depending on the response and if the bottle remained unopened for a&#xD;
      designated period post dosing. Phone based outreach used problem solving discussion with an&#xD;
      adherence coach, who could use an agreed-upon contact tree to reach the youth through other&#xD;
      individuals. This &quot;boot camp&quot; strategy was used to unsettle or disrupt established&#xD;
      non-adherence behaviors and factors promoting ongoing non-adherence.&#xD;
&#xD;
      Participants were followed for 48 weeks, with clinic visits at entry and weeks 4, 12, 24, 36&#xD;
      and 48. Audio computer assisted self-interviews (ACASI) were conducted every 12 weeks to&#xD;
      collect information on adherence, motivation and skills, social support, mental and physical&#xD;
      health functioning. Viral loads, medication and medical histories were also collected at each&#xD;
      study visit.&#xD;
&#xD;
      The primary objective of the study was to compare HIV-virologic suppression (VLS) rates at 12&#xD;
      weeks. Secondary objectives included comparing VLS rates and EDM rates of ART adherence at&#xD;
      24, 36, and 48 weeks as well as patterns of adherence over time.&#xD;
&#xD;
      Major changes after the start of enrollment:&#xD;
&#xD;
        1. To address lower than anticipated enrollment, the requirement that participants be&#xD;
           failing first line ART was dropped in Protocol Version 2.0 (May 9, 2018).&#xD;
&#xD;
        2. Accrual was closed before reaching the target enrollment of 120 participants on the&#xD;
           recommendation of the Study Monitoring Committee (September 30, 2019).&#xD;
&#xD;
        3. Coronavirus disease of 2019 (COVID-19) Updates: On March 20, 2020, the TERA study&#xD;
           suspended all study activities due to COVID-19. On May 5, 2020, sites were allowed to&#xD;
           resume TERA study activities whenever their institution allowed human subjects research&#xD;
           to resume. Participants were encouraged to return for their final Week 48 clinic visits.&#xD;
&#xD;
      At the time of the study pause, data collection for the Primary Outcome Measures was&#xD;
      complete, so the analyses proposed in the original Statistical Analysis Plan were not&#xD;
      affected. Follow-up for the Secondary Outcome Measures involving HIV-1 RNA measurements and&#xD;
      adherence was incomplete, with 33% of participants still on study. Because of the possibility&#xD;
      that participant behavior and adherence to ART would differ pre- and post-pandemic, and it&#xD;
      would not be possible to collect HIV-1 RNA measurements within the required visit windows&#xD;
      (sites were actively trying to keep patients from coming into care unless urgently needed),&#xD;
      the Study Team decided to base analyses on data collected prior to the COVID-19 study pause.&#xD;
      In addition, because the secondary virologic outcome measures were a combination of HIV-1 RNA&#xD;
      levels and data completeness (classifying participants with no HIV-1 RNA measurement within&#xD;
      the allowed visit window as &quot;virologic failures&quot;), the analysis population for these outcome&#xD;
      measures only included participants with sufficient time on study to reach each study visit.&#xD;
&#xD;
      These changes were implemented on June 2, 2020 in a Letter of Amendment (LOA) to TERA&#xD;
      Protocol Version 3.1. The LOA detailed three modifications due to COVID-19 study visit&#xD;
      suspension, but did not affect the existing protocol:&#xD;
&#xD;
        1. Extension of Week 48 visit window through the end of data collection (October 12, 2020)&#xD;
           for participants on-study as of March 20, 2020, due to COVID-19 study suspension.&#xD;
&#xD;
        2. Changed all secondary outcome measures to apply only to data collected prior to COVID-19&#xD;
           study suspension on March 20, 2020. Only participants who had been on study long enough&#xD;
           to reach the Week 24, 36 or 48 study visits were included in the analyses.&#xD;
&#xD;
        3. Virtual/remote site monitoring was implemented for all remaining site monitoring visits.&#xD;
&#xD;
      On September 24, 2020, the Study Team released a memo to the sites extending the date for the&#xD;
      Week 48 study visit to October 12, 2020.&#xD;
&#xD;
      Results for secondary outcome measures 3 to 8 are based on the pre COVID-19 study pause&#xD;
      database as of March 20, 2020.&#xD;
&#xD;
      Results for secondary outcome measures 9 and 10 are based on the complete study database as&#xD;
      of October 12, 2020.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 12, 2018</start_date>
  <completion_date type="Actual">October 12, 2020</completion_date>
  <primary_completion_date type="Actual">January 6, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a Phase II, two-arm, randomized, open-label study.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Plasma Human Immunodeficiency Virus - Type I Ribonucleic Acid (HIV-1 RNA) Levels Less Than (&lt;) 50 Copies/mL at Week 12</measure>
    <time_frame>12 weeks post enrollment</time_frame>
    <description>Participants with HIV-1 RNA &lt; 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA &gt;= 50 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Week 12</measure>
    <time_frame>12 weeks post enrollment</time_frame>
    <description>Participants with HIV-1 RNA &lt; 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 50 Copies/mL at Weeks 24, 36 and 48</measure>
    <time_frame>24, 36 and 48 weeks post enrollment</time_frame>
    <description>Participants with HIV-1 RNA &lt; 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA &gt;= 50 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Weeks 24, 36 and 48</measure>
    <time_frame>24, 36 and 48 weeks post enrollment</time_frame>
    <description>Participants with HIV-1 RNA &lt; 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks</measure>
    <time_frame>48 weeks post enrollment</time_frame>
    <description>Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are &lt; 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is &lt; 200 copies/mL. Otherwise, the participant is classified as a failure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days With Dose Taken From Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</measure>
    <time_frame>Enrollment through 48 weeks</time_frame>
    <description>For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken divided by the number of days with data reported in the Electronic Monitoring Device (EDM).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days With Dose Taken Within Defined Acceptable Window (+/- 4 Hours) From Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</measure>
    <time_frame>Enrollment through 48 weeks</time_frame>
    <description>For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken within acceptable window divided by the number of days with data reported in the EDM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence Rate of 7-day Gaps Between Dosing for Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</measure>
    <time_frame>Enrollment through 48 weeks</time_frame>
    <description>For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of 7-day gaps between doses relative to the number of weeks with data reported, times 12. Consecutive gaps of more than 7 days increase the gap count by one, e.g., missing 20 days counts as 2 gaps.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Week 48</measure>
    <time_frame>48 weeks post enrollment</time_frame>
    <description>Participants with HIV-1 RNA &lt; 200 copies/mL at Week 48 are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or with no HIV-1 RNA measurement after 44 weeks follow-up are classified as failures.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks</measure>
    <time_frame>12, 24, 36, and 48 weeks post enrollment</time_frame>
    <description>Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are &lt; 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is &lt; 200 copies/mL. Otherwise, the participant is classified as a failure.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of Care for adherence support at Site</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TERA Intervention (TERA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>TERA Intervention (TERA)</intervention_name>
    <description>A sequence of adherence support strategies implemented at care visits and as needed on the basis of EDM data. Components include: (1) remote education/preparation with an adherence coach conducted with VSee software (video conferencing) at site at baseline, week 4 and week 12; (2) one-way text alert at dose time when bottle has not yet been opened for that dosing window (users can disable this on request); (3) missed dose two-way outreach text asking &quot;What's the plan?&quot; which gets sent to both the participant's phone and a study phone; and (4) implementation of the coach-outreach (phone, text, remote counseling) triggered by missed doses or as a check-in to inquire about the well-being of the youth (once per week when no other contact with coach occurred the week prior).</description>
    <arm_group_label>TERA Intervention (TERA)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Standard of Care (SOC)</intervention_name>
    <description>Cell-phone reminders, patient-education, adherence planning (medication management), and checking-in on adherence at clinical care visits, as well as Viral load (VL) monitoring with patient feedback on VL, are used at sites. Less common, but available as a general service at some sites, on several websites, and at many pharmacies, youth may also receive text messages at dose times, for appointment reminders, and for refill reminders.</description>
    <arm_group_label>Standard of Care (SOC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Confirmation of HIV-1 Infection as documented in the participant's medical record by&#xD;
             at least two of the following criteria:&#xD;
&#xD;
               -  Reactive HIV screening test result with an HIV antibody or HIV&#xD;
                  antibody/antigen-based, Food and Drug Administration (FDA)-licensed assay&#xD;
                  followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1&#xD;
                  indirect immunofluorescence, HIV-1/HIV-2 discriminatory immunoassay);&#xD;
&#xD;
               -  Plasma HIV-1 quantitative ribonucleic acid (RNA) assay &gt;1,000 copies/mL;&#xD;
&#xD;
               -  Positive HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assay;&#xD;
                  or&#xD;
&#xD;
               -  Positive plasma HIV-1 RNA qualitative assay&#xD;
&#xD;
          2. Participant aware of his or her HIV infection, as determined by site staff&#xD;
&#xD;
          3. Documented plasma HIV-1 RNA plasma ≥200 copies/mL within 45 days of the date of the&#xD;
             enrollment visit&#xD;
&#xD;
          4. Prescribed antiretroviral therapy for at least 24 weeks or more prior to documented&#xD;
             plasma HIV-1 RNA plasma ≥200 copies/mL.&#xD;
&#xD;
          5. Prescribed a once-daily (one or more pills once a day) ART regimen with at least two&#xD;
             active agents (per clinician judgment or genotype evidence) at enrollment&#xD;
&#xD;
          6. Able to communicate in spoken and written English&#xD;
&#xD;
          7. Currently has a cellular phone that is also able to send and receive text messages&#xD;
&#xD;
          8. Willing and able to provide at least one additional contact phone number (preferably&#xD;
             two) to contact participant&#xD;
&#xD;
          9. Able and willing to provide written informed assent/consent and able to obtain written&#xD;
             parental or guardian permission (if required as specified by the site, by state law,&#xD;
             and/or Institutional Review Board policy, and detailed in each site's Protocol&#xD;
             Implementation Plans) to be screened for and to enroll in this study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Gross cognitive limitations, acute emotional instability, or medical or mental health&#xD;
             illness that in the opinion of site personnel would impair the individual's ability to&#xD;
             provide informed consent and/or interfere with the protocol's objectives&#xD;
&#xD;
          2. Concurrent participation in interventional studies addressing adherence unless&#xD;
             approved in advance by study team&#xD;
&#xD;
          3. Positive pregnancy test at the time of enrollment. If participant becomes pregnant&#xD;
             while on study, they may continue on study&#xD;
&#xD;
          4. Currently using or planning to use an electronic dose monitoring and reminder device&#xD;
             outside of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>24 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>K. Rivet Amico, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Hudgens, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Aditya H Gaur, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Denver Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broward Health Childrens Diagnostic and Treatment Center (CDTC)</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Center for HIV/AIDS, Research, Education &amp; Service</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University School of Medicine</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronx-Lebanon Hospital Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Amico KR, Dunlap A, Dallas R, Lindsey J, Heckman B, Flynn P, Lee S, Horvath K, West Goolsby R, Hudgens M, Filipowicz T, Polier M, Hill E, Mueller Johnson M, Miller J, Neilan A, Ciaranello A, Gaur A. Triggered Escalating Real-Time Adherence Intervention to Promote Rapid HIV Viral Suppression Among Youth Living With HIV Failing Antiretroviral Therapy: Protocol for a Triggered Escalating Real-Time Adherence Intervention. JMIR Res Protoc. 2019 Mar 18;8(3):e11416. doi: 10.2196/11416.</citation>
    <PMID>30882360</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <results_first_submitted>October 28, 2020</results_first_submitted>
  <results_first_submitted_qc>December 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 8, 2021</results_first_posted>
  <last_update_submitted>February 18, 2021</last_update_submitted>
  <last_update_submitted_qc>February 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adherence, Medication</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT03292432/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Protocol Version 3.1</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT03292432/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Letter of Amendment to Study Protocol Version 3.1</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT03292432/Prot_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 10 sites in the United States between April 12, 2018 and September 30, 2019.</recruitment_details>
      <pre_assignment_details>Participants were stratified by age (&lt; 18 years vs. &gt;= 18 years) and randomized equally to the TERA intervention and Standard of Care. One participant was randomized but never started a behavioral intervention as site closed before any data collected.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Standard of Care (SOC)</title>
          <description>Standard of care for adherence support at site</description>
        </group>
        <group group_id="P2">
          <title>TERA Intervention (TERA)</title>
          <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Started Study Intervention</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Site closed before any data collected</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Includes participants who started study intervention</population>
      <group_list>
        <group group_id="B1">
          <title>Standard of Care (SOC)</title>
          <description>Standard of care for adherence support at site</description>
        </group>
        <group group_id="B2">
          <title>TERA Intervention (TERA)</title>
          <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="45"/>
            <count group_id="B2" value="43"/>
            <count group_id="B3" value="88"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.1" lower_limit="16.5" upper_limit="24.8"/>
                    <measurement group_id="B2" value="22.3" lower_limit="13.7" upper_limit="24.8"/>
                    <measurement group_id="B3" value="22.2" lower_limit="13.7" upper_limit="24.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>13 - 17 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18 - 21 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>22 - 25 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Sex assigned at birth</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mode of transmission</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Horizontal transmission</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Vertical transmission</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>200 - &lt;400 copies/mL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>400 - &lt;10,000 copies/mL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>10,000 - &lt;50,000 copies/mL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;= 50,000 copies/mL</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cluster of differentiation 4 (CD4) cell count</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt; 200 cells/mm^3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>200 - &lt; 500 cells/mm^3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>500 - &lt; 1000 cells/mm^3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;= 1000 cells/mm^3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Plasma Human Immunodeficiency Virus - Type I Ribonucleic Acid (HIV-1 RNA) Levels Less Than (&lt;) 50 Copies/mL at Week 12</title>
        <description>Participants with HIV-1 RNA &lt; 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA &gt;= 50 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.</description>
        <time_frame>12 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Plasma Human Immunodeficiency Virus - Type I Ribonucleic Acid (HIV-1 RNA) Levels Less Than (&lt;) 50 Copies/mL at Week 12</title>
          <description>Participants with HIV-1 RNA &lt; 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA &gt;= 50 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.</description>
          <population>Includes participants who started study intervention</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.4"/>
                    <measurement group_id="O2" value="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.80</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>-3.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-21.8</ci_lower_limit>
            <ci_upper_limit>15.2</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants achieving HIV-1 RNA &lt; 50 copies/mL in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Week 12</title>
        <description>Participants with HIV-1 RNA &lt; 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.</description>
        <time_frame>12 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Week 12</title>
          <description>Participants with HIV-1 RNA &lt; 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.</description>
          <population>Includes participants who started study intervention</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.6"/>
                    <measurement group_id="O2" value="34.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>-0.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20.9</ci_lower_limit>
            <ci_upper_limit>19.6</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants achieving HIV-1 RNA &lt; 200 copies/ml in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 50 Copies/mL at Weeks 24, 36 and 48</title>
        <description>Participants with HIV-1 RNA &lt; 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA &gt;= 50 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.</description>
        <time_frame>24, 36 and 48 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention and with the opportunity to reach the targeted study visit prior to the Coronavirus Disease 2019 (COVID-19) study pause on March 20, 2020</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 50 Copies/mL at Weeks 24, 36 and 48</title>
          <description>Participants with HIV-1 RNA &lt; 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA &gt;= 50 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.</description>
          <population>Includes participants who started study intervention and with the opportunity to reach the targeted study visit prior to the Coronavirus Disease 2019 (COVID-19) study pause on March 20, 2020</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.4"/>
                    <measurement group_id="O2" value="23.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                    <count group_id="O2" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.6"/>
                    <measurement group_id="O2" value="19.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.0"/>
                    <measurement group_id="O2" value="27.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages at Week 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.24</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>-13.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-32.1</ci_lower_limit>
            <ci_upper_limit>7.2</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 50 copies/mL at Week 24 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages at Week 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.76</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>3.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.0</ci_lower_limit>
            <ci_upper_limit>22.6</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 50 copies/mL at Week 36 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages at Week 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>3.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-21.8</ci_lower_limit>
            <ci_upper_limit>27.4</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 50 copies/mL at Week 48 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Weeks 24, 36 and 48</title>
        <description>Participants with HIV-1 RNA &lt; 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.</description>
        <time_frame>24, 36 and 48 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention and with the opportunity to reach the targeted study visit prior to the COVID-19 study pause on March 20, 2020</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Weeks 24, 36 and 48</title>
          <description>Participants with HIV-1 RNA &lt; 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.</description>
          <population>Includes participants who started study intervention and with the opportunity to reach the targeted study visit prior to the COVID-19 study pause on March 20, 2020</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.9"/>
                    <measurement group_id="O2" value="27.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                    <count group_id="O2" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.9"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                    <count group_id="O2" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.0"/>
                    <measurement group_id="O2" value="27.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages at Week 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.26</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>-13.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-32.7</ci_lower_limit>
            <ci_upper_limit>7.3</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 200 copies/mL at Week 24 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages at Week 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.42</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>11.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.2</ci_lower_limit>
            <ci_upper_limit>32.8</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 200 copies/mL at Week 36 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages at Week 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.77</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>-4.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-29.5</ci_lower_limit>
            <ci_upper_limit>20.7</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 200 copies/mL at Week 48 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks</title>
        <description>Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are &lt; 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is &lt; 200 copies/mL. Otherwise, the participant is classified as a failure.</description>
        <time_frame>48 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention and with the opportunity to reach the Week 48 visit prior to the COVID-19 study pause on March 20, 2020</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks</title>
          <description>Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are &lt; 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is &lt; 200 copies/mL. Otherwise, the participant is classified as a failure.</description>
          <population>Includes participants who started study intervention and with the opportunity to reach the Week 48 visit prior to the COVID-19 study pause on March 20, 2020</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0"/>
                    <measurement group_id="O2" value="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.67</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>5.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-14.6</ci_lower_limit>
            <ci_upper_limit>25.3</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants with HIV-1 RNA &lt; 200 copies/mL at Week 12 and maintained to Week 48 in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days With Dose Taken From Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</title>
        <description>For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken divided by the number of days with data reported in the Electronic Monitoring Device (EDM).</description>
        <time_frame>Enrollment through 48 weeks</time_frame>
        <population>Includes participants who started study intervention and with data reported in the adherence EDM up to the COVID-19 pause on March 20, 2020</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days With Dose Taken From Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</title>
          <description>For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken divided by the number of days with data reported in the Electronic Monitoring Device (EDM).</description>
          <population>Includes participants who started study intervention and with data reported in the adherence EDM up to the COVID-19 pause on March 20, 2020</population>
          <units>Percentage of days with dose taken</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Weeks 0 - 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.0" lower_limit="20.5" upper_limit="59.0"/>
                    <measurement group_id="O2" value="72.1" lower_limit="46.5" upper_limit="89.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;12 - 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3" lower_limit="1.2" upper_limit="32.1"/>
                    <measurement group_id="O2" value="40.5" lower_limit="10.7" upper_limit="70.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;24 - 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="0.0" upper_limit="14.3"/>
                    <measurement group_id="O2" value="17.2" lower_limit="2.3" upper_limit="40.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;36 - 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                    <count group_id="O2" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="0.0" upper_limit="7.4"/>
                    <measurement group_id="O2" value="1.2" lower_limit="0.0" upper_limit="30.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages of doses taken from Weeks 0 -12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentage of doses taken from Weeks &gt;12 to 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentage of doses taken from Weeks &gt;24 to 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.06</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentage of doses taken from Weeks &gt;36 to 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.50</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days With Dose Taken Within Defined Acceptable Window (+/- 4 Hours) From Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</title>
        <description>For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken within acceptable window divided by the number of days with data reported in the EDM.</description>
        <time_frame>Enrollment through 48 weeks</time_frame>
        <population>Includes participants who started study intervention and with data reported in the adherence EDM up to the COVID-19 pause on March 20, 2020</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days With Dose Taken Within Defined Acceptable Window (+/- 4 Hours) From Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</title>
          <description>For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken within acceptable window divided by the number of days with data reported in the EDM.</description>
          <population>Includes participants who started study intervention and with data reported in the adherence EDM up to the COVID-19 pause on March 20, 2020</population>
          <units>Percentage of days dose taken on time</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Weeks 0 - 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.4" lower_limit="8.4" upper_limit="38.6"/>
                    <measurement group_id="O2" value="62.7" lower_limit="30.1" upper_limit="84.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;12 - 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" lower_limit="0.0" upper_limit="16.7"/>
                    <measurement group_id="O2" value="27.4" lower_limit="7.1" upper_limit="57.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;24 - 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="0.0" upper_limit="9.5"/>
                    <measurement group_id="O2" value="10.7" lower_limit="0.0" upper_limit="35.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;36 - 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                    <count group_id="O2" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.0" upper_limit="4.8"/>
                    <measurement group_id="O2" value="1.2" lower_limit="0.0" upper_limit="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentage of doses taken on time from Weeks 0 - 12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentage of doses taken on time from Weeks &gt;12 - 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of percentages of doses taken on time from Weeks &gt;24 - 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.05</p_value>
            <p_value_desc>p-value equal to a priori threshold for statistical significance</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of doses taken on time from Weeks &gt;36 - 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.49</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence Rate of 7-day Gaps Between Dosing for Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</title>
        <description>For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of 7-day gaps between doses relative to the number of weeks with data reported, times 12. Consecutive gaps of more than 7 days increase the gap count by one, e.g., missing 20 days counts as 2 gaps.</description>
        <time_frame>Enrollment through 48 weeks</time_frame>
        <population>Includes participants who started study intervention and with data reported in the adherence EDM up to the COVID-19 pause on March 20, 2020.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence Rate of 7-day Gaps Between Dosing for Weeks 0-12, &gt;12-24, &gt;24-36 and &gt;36-48</title>
          <description>For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of 7-day gaps between doses relative to the number of weeks with data reported, times 12. Consecutive gaps of more than 7 days increase the gap count by one, e.g., missing 20 days counts as 2 gaps.</description>
          <population>Includes participants who started study intervention and with data reported in the adherence EDM up to the COVID-19 pause on March 20, 2020.</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Weeks 0 - 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.17" lower_limit="3.61" upper_limit="4.82"/>
                    <measurement group_id="O2" value="1.66" lower_limit="1.31" upper_limit="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;12 - 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="45"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.91" lower_limit="6.16" upper_limit="7.75"/>
                    <measurement group_id="O2" value="4.43" lower_limit="3.81" upper_limit="5.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;24 - 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.19" lower_limit="7.28" upper_limit="9.21"/>
                    <measurement group_id="O2" value="6.65" lower_limit="5.84" upper_limit="7.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weeks &gt;36 - 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                    <count group_id="O2" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.54" lower_limit="8.37" upper_limit="10.89"/>
                    <measurement group_id="O2" value="8.81" lower_limit="7.76" upper_limit="10.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of incidence rates from Weeks 0 - 12</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Chi-squared</method>
            <method_desc>Pearson Chi-square test from generalized linear model with Poisson link</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>2.51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.90</ci_lower_limit>
            <ci_upper_limit>3.33</ci_upper_limit>
            <estimate_desc>Risk ratio for SOC arm relative to TERA arm</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of incidence rates from Weeks &gt;12 - 24</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Chi-squared</method>
            <method_desc>Pearson Chi-square test from generalized linear model with Poisson link</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.56</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.29</ci_lower_limit>
            <ci_upper_limit>1.89</ci_upper_limit>
            <estimate_desc>Risk ratio for SOC arm relative to TERA arm</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of incidence rates from Weeks &gt;24 - 36</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.020</p_value>
            <method>Chi-squared</method>
            <method_desc>Pearson Chi-square test from generalized linear model with Poisson link</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.03</ci_lower_limit>
            <ci_upper_limit>1.47</ci_upper_limit>
            <estimate_desc>P-value from Pearson Chi-square test from generalized linear model with Poisson link</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of incidence rates from Weeks &gt;36 - 48</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.39</p_value>
            <method>Chi-squared</method>
            <method_desc>Pearson Chi-square test from generalized linear model with Poisson link</method_desc>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.90</ci_lower_limit>
            <ci_upper_limit>1.30</ci_upper_limit>
            <estimate_desc>Risk ratio for SOC arm relative to TERA arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Week 48</title>
        <description>Participants with HIV-1 RNA &lt; 200 copies/mL at Week 48 are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or with no HIV-1 RNA measurement after 44 weeks follow-up are classified as failures.</description>
        <time_frame>48 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention. Excludes participants who died from non-HIV-related causes before Week 48.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at Week 48</title>
          <description>Participants with HIV-1 RNA &lt; 200 copies/mL at Week 48 are classified as successes. Participants with HIV-1 RNA &gt;= 200 copies/mL or with no HIV-1 RNA measurement after 44 weeks follow-up are classified as failures.</description>
          <population>Includes participants who started study intervention. Excludes participants who died from non-HIV-related causes before Week 48.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.3"/>
                    <measurement group_id="O2" value="25.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>2.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.4</ci_lower_limit>
            <ci_upper_limit>21.1</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants achieving HIV-1 RNA &lt; 200 copies/mL in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks</title>
        <description>Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are &lt; 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is &lt; 200 copies/mL. Otherwise, the participant is classified as a failure.</description>
        <time_frame>12, 24, 36, and 48 weeks post enrollment</time_frame>
        <population>Includes participants who started study intervention. Excludes participants who died from non-HIV-related causes before Week 48.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC)</title>
            <description>Standard of care for adherence support at site</description>
          </group>
          <group group_id="O2">
            <title>TERA Intervention (TERA)</title>
            <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With HIV-1 RNA &lt; 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks</title>
          <description>Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are &lt; 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is &lt; 200 copies/mL. Otherwise, the participant is classified as a failure.</description>
          <population>Includes participants who started study intervention. Excludes participants who died from non-HIV-related causes before Week 48.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0"/>
                    <measurement group_id="O2" value="11.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.71</p_value>
            <method>Fisher Exact</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>4.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.0</ci_lower_limit>
            <ci_upper_limit>19.4</ci_upper_limit>
            <estimate_desc>Risk difference reflects percentage of participants achieving sustained virologic control in TERA arm minus SOC arm</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From study entry to study completion (approximately 48 weeks)</time_frame>
      <desc>In addition to collection of serious adverse events, the study collected 'Untoward events' of Grade 3 or higher and related to the study. Untoward events were defined as unexpected occurrences involving study participants, study staff, or the community where the study was taking place, that may reasonably be judged as related to study procedures and that led to harm, distress, or increased risk of harm or distress, but that did not otherwise meet the definition of an adverse event.</desc>
      <group_list>
        <group group_id="E1">
          <title>Standard of Care (SOC)</title>
          <description>Standard of care for adherence support at site</description>
        </group>
        <group group_id="E2">
          <title>TERA Intervention (TERA)</title>
          <description>Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac event</sub_title>
                <description>Resulted in death</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Esophageal candidiasis and pelvic inflammatory disease</sub_title>
                <description>Resulted in hospitalization</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Axillary abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>HSV proctitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Facial cellulitis and MRSA positive wound of the tragus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>AIDS</sub_title>
                <description>Resulted in death</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Gunshot wound to head</sub_title>
                <description>Resulted in death</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax acute recurrent with shortness of breath, hypoxia and hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Accrual was closed before reaching the targeted enrollment of 120 participants. Study visits were paused on March 20, 2020 due to the outbreak of COVID-19, interrupting systematic collection of secondary outcome measures. Statistical comparisons between arms therefore had lower than anticipated power to detect differences. For EDM data, the time the device was opened can only be assumed to correspond with when the participant took their antiretroviral dose.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Rachel Goolsby - Research Manager</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>9198430685</phone>
      <email>rwgoolsby@unc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03292432
org study id: ATN 152
secondary id: 5U24HD089880-02
nct id: NCT03292432
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
Youth Living with HIV (YLWH) often face unique challenges achieving high and sustained rates
      of adherence to their antiretroviral therapy (ART). Poor adherence can lead to unsuppressed
      virus, more advanced HIV disease and poorer health outcomes, eventually exhausting treatment
      options. To date however, there are few demonstrated interventions for youth failing first
      line therapy. This study evaluated a novel intervention that used remote coaching through
      video enabled counseling sessions, an Electronic Dose Monitoring (EDM) pill bottle that
      notified an adherence coach when youth failed to open/close the device around dose time, and
      problem solving outreach by the coach in response to not dosing from the EDM. This intensive
      'boot camp' strategy was implemented for 12 weeks followed by observation through 48 weeks.
This was a Phase II, two-arm, randomized, open-label study. Eligible participants had failed
      ART therapy, defined as having a detectable plasma Human Immunodeficiency Virus - Type 1
      Ribonucleic Acid (HIV-1 RNA) ≥200 copies/ml within 45 days of enrollment despite having been
      prescribed ART for at least 24 weeks. They could continue the same ART regimen or start a new
      once daily regimen. Participants were stratified by age (<18 vs. ≥18 years of age) and
      randomized in equal proportions to receive the study intervention (TERA) or standard of care
      (SOC), with no enrollment limits in each stratum. Target accrual was 120 participants to be
      enrolled over one year.

      TERA was a time-limited (12 weeks) intervention approach that (a) used wireless electronic
      dose monitoring (EDM) to identify dose-times passing with no bottle opening, (b) sent a text
      asking about the delay, (c) evaluated response to the text and (d) initiated follow-up by an
      adherence coach depending on the response and if the bottle remained unopened for a
      designated period post dosing. Phone based outreach used problem solving discussion with an
      adherence coach, who could use an agreed-upon contact tree to reach the youth through other
      individuals. This "boot camp" strategy was used to unsettle or disrupt established
      non-adherence behaviors and factors promoting ongoing non-adherence.

      Participants were followed for 48 weeks, with clinic visits at entry and weeks 4, 12, 24, 36
      and 48. Audio computer assisted self-interviews (ACASI) were conducted every 12 weeks to
      collect information on adherence, motivation and skills, social support, mental and physical
      health functioning. Viral loads, medication and medical histories were also collected at each
      study visit.

      The primary objective of the study was to compare HIV-virologic suppression (VLS) rates at 12
      weeks. Secondary objectives included comparing VLS rates and EDM rates of ART adherence at
      24, 36, and 48 weeks as well as patterns of adherence over time.

      Major changes after the start of enrollment:

        1. To address lower than anticipated enrollment, the requirement that participants be
           failing first line ART was dropped in Protocol Version 2.0 (May 9, 2018).

        2. Accrual was closed before reaching the target enrollment of 120 participants on the
           recommendation of the Study Monitoring Committee (September 30, 2019).

        3. Coronavirus disease of 2019 (COVID-19) Updates: On March 20, 2020, the TERA study
           suspended all study activities due to COVID-19. On May 5, 2020, sites were allowed to
           resume TERA study activities whenever their institution allowed human subjects research
           to resume. Participants were encouraged to return for their final Week 48 clinic visits.

      At the time of the study pause, data collection for the Primary Outcome Measures was
      complete, so the analyses proposed in the original Statistical Analysis Plan were not
      affected. Follow-up for the Secondary Outcome Measures involving HIV-1 RNA measurements and
      adherence was incomplete, with 33% of participants still on study. Because of the possibility
      that participant behavior and adherence to ART would differ pre- and post-pandemic, and it
      would not be possible to collect HIV-1 RNA measurements within the required visit windows
      (sites were actively trying to keep patients from coming into care unless urgently needed),
      the Study Team decided to base analyses on data collected prior to the COVID-19 study pause.
      In addition, because the secondary virologic outcome measures were a combination of HIV-1 RNA
      levels and data completeness (classifying participants with no HIV-1 RNA measurement within
      the allowed visit window as "virologic failures"), the analysis population for these outcome
      measures only included participants with sufficient time on study to reach each study visit.

      These changes were implemented on June 2, 2020 in a Letter of Amendment (LOA) to TERA
      Protocol Version 3.1. The LOA detailed three modifications due to COVID-19 study visit
      suspension, but did not affect the existing protocol:

        1. Extension of Week 48 visit window through the end of data collection (October 12, 2020)
           for participants on-study as of March 20, 2020, due to COVID-19 study suspension.

        2. Changed all secondary outcome measures to apply only to data collected prior to COVID-19
           study suspension on March 20, 2020. Only participants who had been on study long enough
           to reach the Week 24, 36 or 48 study visits were included in the analyses.

        3. Virtual/remote site monitoring was implemented for all remaining site monitoring visits.

      On September 24, 2020, the Study Team released a memo to the sites extending the date for the
      Week 48 study visit to October 12, 2020.

      Results for secondary outcome measures 3 to 8 are based on the pre COVID-19 study pause
      database as of March 20, 2020.

      Results for secondary outcome measures 9 and 10 are based on the complete study database as
      of October 12, 2020.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a Phase II, two-arm, randomized, open-label study.
primary purpose: Supportive Care
masking: None (Open Label)
measure: Percentage of Participants With Plasma Human Immunodeficiency Virus - Type I Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/mL at Week 12
time frame: 12 weeks post enrollment
description: Participants with HIV-1 RNA < 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA >= 50 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 12
time frame: 12 weeks post enrollment
description: Participants with HIV-1 RNA < 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA >= 200 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24, 36 and 48
time frame: 24, 36 and 48 weeks post enrollment
description: Participants with HIV-1 RNA < 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA >= 50 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.
measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Weeks 24, 36 and 48
time frame: 24, 36 and 48 weeks post enrollment
description: Participants with HIV-1 RNA < 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA >= 200 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.
measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks
time frame: 48 weeks post enrollment
description: Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are < 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is < 200 copies/mL. Otherwise, the participant is classified as a failure.
measure: Percentage of Days With Dose Taken From Weeks 0-12, >12-24, >24-36 and >36-48
time frame: Enrollment through 48 weeks
description: For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken divided by the number of days with data reported in the Electronic Monitoring Device (EDM).
measure: Percentage of Days With Dose Taken Within Defined Acceptable Window (+/- 4 Hours) From Weeks 0-12, >12-24, >24-36 and >36-48
time frame: Enrollment through 48 weeks
description: For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken within acceptable window divided by the number of days with data reported in the EDM.
measure: Incidence Rate of 7-day Gaps Between Dosing for Weeks 0-12, >12-24, >24-36 and >36-48
time frame: Enrollment through 48 weeks
description: For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of 7-day gaps between doses relative to the number of weeks with data reported, times 12. Consecutive gaps of more than 7 days increase the gap count by one, e.g., missing 20 days counts as 2 gaps.
measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48
time frame: 48 weeks post enrollment
description: Participants with HIV-1 RNA < 200 copies/mL at Week 48 are classified as successes. Participants with HIV-1 RNA >= 200 copies/mL or with no HIV-1 RNA measurement after 44 weeks follow-up are classified as failures.
measure: Percentage of Participants With HIV-1 RNA < 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks
time frame: 12, 24, 36, and 48 weeks post enrollment
description: Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are < 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is < 200 copies/mL. Otherwise, the participant is classified as a failure.
arm group label: Standard of Care (SOC)
arm group type: Active Comparator
description: Standard of Care for adherence support at Site
arm group label: TERA Intervention (TERA)
arm group type: Experimental
description: Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks.
intervention type: Behavioral
intervention name: TERA Intervention (TERA)
description: A sequence of adherence support strategies implemented at care visits and as needed on the basis of EDM data. Components include: (1) remote education/preparation with an adherence coach conducted with VSee software (video conferencing) at site at baseline, week 4 and week 12; (2) one-way text alert at dose time when bottle has not yet been opened for that dosing window (users can disable this on request); (3) missed dose two-way outreach text asking "What's the plan?" which gets sent to both the participant's phone and a study phone; and (4) implementation of the coach-outreach (phone, text, remote counseling) triggered by missed doses or as a check-in to inquire about the well-being of the youth (once per week when no other contact with coach occurred the week prior).
arm group label: TERA Intervention (TERA)
intervention type: Behavioral
intervention name: Standard of Care (SOC)
description: Cell-phone reminders, patient-education, adherence planning (medication management), and checking-in on adherence at clinical care visits, as well as Viral load (VL) monitoring with patient feedback on VL, are used at sites. Less common, but available as a general service at some sites, on several websites, and at many pharmacies, youth may also receive text messages at dose times, for appointment reminders, and for refill reminders.
arm group label: Standard of Care (SOC)
criteria: 
gender: All
minimum age: 13 Years
maximum age: 24 Years
healthy volunteers: Accepts Healthy Volunteers
last name: K. Rivet Amico, PhD
role: Principal Investigator
affiliation: University of Michigan School of Public Health
last name: Michael Hudgens, PhD
role: Study Director
affiliation: University of North Carolina, Chapel Hill
last name: Aditya H Gaur, MD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
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country: United States
citation: Amico KR, Dunlap A, Dallas R, Lindsey J, Heckman B, Flynn P, Lee S, Horvath K, West Goolsby R, Hudgens M, Filipowicz T, Polier M, Hill E, Mueller Johnson M, Miller J, Neilan A, Ciaranello A, Gaur A. Triggered Escalating Real-Time Adherence Intervention to Promote Rapid HIV Viral Suppression Among Youth Living With HIV Failing Antiretroviral Therapy: Protocol for a Triggered Escalating Real-Time Adherence Intervention. JMIR Res Protoc. 2019 Mar 18;8(3):e11416. doi: 10.2196/11416.
PMID: 30882360
responsible party type: Sponsor
mesh term: HIV Infections
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Accrual was closed before reaching the targeted enrollment of 120 participants. Study visits were paused on March 20, 2020 due to the outbreak of COVID-19, interrupting systematic collection of secondary outcome measures. Statistical comparisons between arms therefore had lower than anticipated power to detect differences. For EDM data, the time the device was opened can only be assumed to correspond with when the participant took their antiretroviral dose.
point of contact: 