<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/NCT03757104</url>
  </required_header>
  <id_info>
    <org_study_id>A0001-BFC398/16</org_study_id>
    <nct_id>NCT03757104</nct_id>
  </id_info>
  <brief_title>Home-based Intervention to Test and Start</brief_title>
  <acronym>HITS</acronym>
  <official_title>Home-based Interventions to Test and Start (HITS): a Cluster-randomized Controlled Trial to Reduce Mortality and Incidence Through HIV Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Africa Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Heidelberg University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>London School of Hygiene and Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Glasgow</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Southampton</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Africa Health Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to establish the causal impact of two interventions - micro-incentives and a&#xD;
      male-sensitive HIV- specific decision support app - on population-level HIV viral load and&#xD;
      HIV-related mortality in men, as well as on population-based HIV incidence in young women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Research aim:&#xD;
&#xD;
      The primary aim of the home-based intervention to test and start (HITS) trial is to establish&#xD;
      whether (i) the provision of two micro-incentives and (ii) a male-sensitive and HIV-specific&#xD;
      decision support app will reduce population-level HIV viral load and HIV-related mortality in&#xD;
      men, as well as population-level HIV incidence in young women.&#xD;
&#xD;
      Specific objectives&#xD;
&#xD;
        1. Establish the causal impact of two micro-incentives (aimed at increasing uptake of&#xD;
           home-based HIV testing and linkage to care, respectively) on:&#xD;
&#xD;
             1. Population-level HIV viral load in men&#xD;
&#xD;
             2. Population-level HIV-related mortality in men&#xD;
&#xD;
             3. Population-level HIV incidence in young women.&#xD;
&#xD;
        2. Establish the causal impact of a male-sensitive and HIV-specific decision- support app&#xD;
           (called EPIC-HIV) on:&#xD;
&#xD;
             1. Population-level HIV viral load in men&#xD;
&#xD;
             2. Population-level HIV-related mortality in men&#xD;
&#xD;
             3. Population-level HIV incidence in young women.&#xD;
&#xD;
        3. Establish the causal impact of the two conditional micro-incentives on:&#xD;
&#xD;
             1. HIV status knowledge in men and women&#xD;
&#xD;
             2. HIV knowledge in men and women&#xD;
&#xD;
             3. HIV treatment knowledge in men and women&#xD;
&#xD;
             4. HIV treatment utilization in men and women&#xD;
&#xD;
             5. Sexual behavior in men and women&#xD;
&#xD;
             6. Healthcare utilization in men and women&#xD;
&#xD;
             7. Household healthcare expenditures&#xD;
&#xD;
             8. Household wealth&#xD;
&#xD;
             9. Retention in HIV care in men and women&#xD;
&#xD;
        4. Establish the causal impact of the male-sensitive HIV-specific decision support app on:&#xD;
&#xD;
             1. HIV status knowledge in men and women&#xD;
&#xD;
             2. HIV knowledge in men and women&#xD;
&#xD;
             3. HIV treatment knowledge in men and women&#xD;
&#xD;
             4. HIV treatment utilization in men and women&#xD;
&#xD;
             5. Sexual behavior in men and women&#xD;
&#xD;
             6. Healthcare utilization in men and women&#xD;
&#xD;
             7. Household healthcare expenditures&#xD;
&#xD;
             8. Household wealth&#xD;
&#xD;
             9. Retention in HIV care in men and women&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      The investigators hypothesize that each of the two interventions - micro-incentives aimed at&#xD;
      encouraging HIV testing and linkage to HIV care and a male-sensitive HIV-specific decision&#xD;
      support app - will each increase HIV testing and HIV treatment uptake and via this mechanism&#xD;
      lead to reduced population viral load and HIV-related mortality particularly in men. Reduced&#xD;
      viral load among men, in turn, will reduce HIV incidence in young women.&#xD;
&#xD;
      Research design Following a formative phase to develop the design of the two HITS&#xD;
      intervention the investigators will determine the causal impact of the interventions on our&#xD;
      three primary endpoints in a 2x2 factorial cluster-randomized controlled trial with a&#xD;
      baseline adjustment. A mixed- methods approach will be employed that combines the strengths&#xD;
      of rapid formative social science research (that will inform the precise delivery of the HITS&#xD;
      intervention) with a causally rigorous statistical methodology to evaluate the effectiveness&#xD;
      of the HITS intervention.&#xD;
&#xD;
      The HITS intervention will be delivered through the Africa Health Research Institute's (AHRI)&#xD;
      existing HIV surveillance operations. The investigators will randomize 45 communities to the&#xD;
      four interventions. 8 communities each will receive one of the interventions&#xD;
      (micro-incentives only, male-sensitive HIV-specific decision support app only); 8 communities&#xD;
      will receive both interventions and 21 communities will receive standard-of-care. Communities&#xD;
      will be stratified by incidence in young women (2004-2016) to derive a similar baseline&#xD;
      incidence across intervention and standard-of-care communities prior to the implementation of&#xD;
      the intervention. Both men and women will be eligible to receive the financial incentives to&#xD;
      test and link to care, whilst only men will be eligible for the EPIC HIV-specific decision&#xD;
      support application.&#xD;
&#xD;
      In the total of 3x8=24 communities in the intervention arms, an estimated total of 4,667&#xD;
      individuals will receive a HITS intervention. In the 21 communities, 4,900 individuals will&#xD;
      receive the standard-of-care. Outcomes will be assessed in all eligible individuals living in&#xD;
      the 45 communities, which together have an estimated population size of 30,000 adults.&#xD;
&#xD;
      Sample size calculation The study was powered using the outcome of HIV incidence in women&#xD;
      aged 15-30. Using actual Africa Health Research Institute HIV incidence data, the&#xD;
      investigators simulated the HITS intervention introduced in 2011 to 24 of the 45 communities&#xD;
      in the study area. The investigators simulated an intervention that led to a 25% reduction in&#xD;
      arm 1 (micro-incentives), 25% reduction in arm 2 (male-sensitive counselling) and a 32%&#xD;
      reduction in the combined arm. Communities were stratified by baseline incidence (three&#xD;
      strata) in young women (2004-2011) to allow for a similar baseline incidence in intervention&#xD;
      and control communities and the investigators included a random effect in the simulations to&#xD;
      adjust for clustering by community. The results show that the investigators would have been&#xD;
      able to detect this reduction in incidence in &gt;80% of simulation replicates (p&lt;0.05).&#xD;
      Therefore, if the investigators were to introduce the HITS intervention in 2018 and follow&#xD;
      young women up for at least 3 years post intervention (ie utilize a total of 17 years of&#xD;
      incidence data - 2004 to 2021) the investigators would be in excess of 90% powered to detect&#xD;
      such a reduction in incidence in this critical age-group.&#xD;
&#xD;
      Research methodology Research site:&#xD;
&#xD;
      The trial will be managed from the Africa Health Research Institute, formerly Africa Centre&#xD;
      that conducts a large longitudinal Demographic and Health surveillance. Participants will be&#xD;
      enrolled during the routine HIV surveillance study (Population Intervention Program) -&#xD;
      trained fieldworkers visit participants at home once a year to conduct household surveys&#xD;
      using tablet computers and offer point of care HIV testing to all individuals aged 15+.&#xD;
&#xD;
      Study procedures:&#xD;
&#xD;
      In those arms of this cluster Randomized Controlled Trial (RCT) that include the once-off&#xD;
      two-stage micro-incentive scheme, consenting men and women will be offered a first&#xD;
      opportunity to earn a R50 food voucher (redeemable in a local supermarket) conditional on HIV&#xD;
      testing. If a participant tests positive for HIV, he/she will have the opportunity to receive&#xD;
      a second R50 food voucher conditional on linking within 6 weeks following the HIV test to one&#xD;
      of the 11 local primary care clinics where HIV treatment and care are available.&#xD;
&#xD;
      In those arms of this cluster RCT that include the male-sensitive HIV-specific decision&#xD;
      support app, men will be offered EPIC-HIV (a first version, so-called EPIC-HIV-1) prior HIV&#xD;
      counseling and testing. EPIC-HIV-1 is aimed at increasing HIV testing uptake. Those&#xD;
      participants who do not link to care within a month of the HIV test will be offered a second&#xD;
      version of EPIC-HIV (so-called EPIC-HIV-2) at home to encourage linkage to care.&#xD;
&#xD;
      Follow up of participants:&#xD;
&#xD;
      Participants will be followed up routinely through the AHRI's ongoing population-based HIV&#xD;
      surveillance. All participants will be followed up for at least 3 years.&#xD;
&#xD;
      Linkage to care will be routinely established via the AHRI's ongoing linkage of clinical&#xD;
      records for all patients in the local public sector ART program in the demographic&#xD;
      surveillance.&#xD;
&#xD;
      Data management: Data will be collected and managed by AHRI Research Data Management within&#xD;
      PIP databases as per AHRI comprehensive study operating procedures (SOPs). The Population&#xD;
      Intervention Platform (PIP) database has strictly restricted access via a data enclave on a&#xD;
      secure server.&#xD;
&#xD;
      Data analysis:&#xD;
&#xD;
      All primary analyses (of both primary and secondary endpoints) will be intent-to-treat (ITT).&#xD;
&#xD;
      For the binary primary outcomes - HIV testing uptake, HIV treatment linkage, and&#xD;
      population-level HIV viral suppression - the investigators will use generalized linear models&#xD;
      with a Poisson distribution, log link function, and robust error terms to determine effect&#xD;
      sizes (risk ratios).&#xD;
&#xD;
      For the two survival-analytical primary endpoints - population-level mortality among men and&#xD;
      population-level HIV incidence among women - the investigators will use the Cox proportional&#xD;
      hazards model to determine effect sizes (hazard ratios). If the proportional hazards&#xD;
      assumption of the Cox model is violated, the investigators will use appropriate alternative&#xD;
      survival analytical models.&#xD;
&#xD;
      In all primary analyses, the investigators will adjust for both baseline endpoints and&#xD;
      clustering. For the survival analytical endpoints, the investigators will use data from the&#xD;
      period 2004-2017 for baseline endpoint adjustment.&#xD;
&#xD;
      In addition, to the ITT analyses, the investigators will measure intervention effects&#xD;
      adjusted for non-compliance using instrumental variable (IV) approaches&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 6, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Factorial Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HIV testing uptake at point of test offer in men</measure>
    <time_frame>Baseline</time_frame>
    <description>% received the rapid HIV test at home among those offered the test in men</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV treatment linkage at 1 year in men</measure>
    <time_frame>year 1</time_frame>
    <description>% who visited study clinics and initiated antiretroviral therapy (ART) in men</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Population-level HIV viral suppression in men</measure>
    <time_frame>year 1</time_frame>
    <description>Change in proportion with detectable viremia in men; HIV testing and viral load measurements are performed on the dried blood spot (DBS) samples collected during the annual survey</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Population-level HIV-related mortality in men</measure>
    <time_frame>year 3</time_frame>
    <description>Change in HIV-related mortality rate measured as the number of HIV-related deaths per 1000 person-years of observation in men</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Population-level HIV incidence in young women (15-30 years of age)</measure>
    <time_frame>year 3</time_frame>
    <description>Change in HIV incidence rate (number of HIV sero-conversions per 100 person-years of follow up) in young women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HIV testing uptake at point of test offer in women</measure>
    <time_frame>Baseline</time_frame>
    <description>% received rapid HIV test at home among those offered the test in women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV treatment linkage at 1 year in women</measure>
    <time_frame>year 1</time_frame>
    <description>% who visited study clinics and initiated ART in women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV viral suppression (both sexes)</measure>
    <time_frame>year 1</time_frame>
    <description>Change in proportion with detectable viremia in both men and women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV viral suppression (both sexes)</measure>
    <time_frame>year 3</time_frame>
    <description>Change in proportion with detectable viremia in both men and women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV viral suppression in women</measure>
    <time_frame>year 1</time_frame>
    <description>Change in proportion with detectable viremia in women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV viral suppression in women</measure>
    <time_frame>year 3</time_frame>
    <description>Change in proportion with detectable viremia in women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV viral suppression in men</measure>
    <time_frame>year 3</time_frame>
    <description>Change in proportion with detectable viremia in men; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population level HIV incidence (both sexes)</measure>
    <time_frame>year 3</time_frame>
    <description>Change in HIV incidence rate (number of HIV sero-conversions per 100 person-years of follow up) in both men and women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV-related mortality (both sexes)</measure>
    <time_frame>year 3</time_frame>
    <description>Change in HIV-related mortality rate measured as the number of HIV-related deaths per 1000 person-years of observation in both men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level all-cause mortality (both sexes)</measure>
    <time_frame>year 3</time_frame>
    <description>Change in all-cause mortality rate measured as the number of all-cause deaths per 1000 person-years of observation in both men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV-related mortality in women</measure>
    <time_frame>year 3</time_frame>
    <description>Change in HIV-related mortality rate measured as the number of HIV-related deaths per 1000 person-years of observation in women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Population-level HIV incidence in men</measure>
    <time_frame>year 3</time_frame>
    <description>Change in HIV incidence rate (number of HIV sero-conversions per 100 person-years of follow up) in men; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV status knowledge in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% ever received a test result for HIV in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV prevention knowledge in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reporting ever hearing about pre-exposure prophylaxis (PrEP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV treatment utilization in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reporting ever taking up ART for own health in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported condom use in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reporting condom use at last sex in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tuberculosis (TB) healthcare utilization in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reported starting TB treatment in the past 12 months in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetes Healthcare utilization in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reported starting diabetes treatment in the past 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypertension healthcare utilization in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reported starting blood pressure treatment in the past 12 months in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Household wealth (household assets)</measure>
    <time_frame>year 3</time_frame>
    <description>Number of household assets (selected from a predefined list of 32 assets)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Household wealth (food security)</measure>
    <time_frame>year 3</time_frame>
    <description>% of adults in the household ever cutting the size of meals or missing meals due to insufficient money for food in the past 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partnership patterns in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% reporting having more than one sexual partner in the past 12 months in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retention in HIV care in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% who are retained in care (% patients having an ART clinic visit in previous 3 months) at 1 year post-initiation in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retention in HIV care in men and women</measure>
    <time_frame>year 3</time_frame>
    <description>% who are retained in care (% patients having an ART clinic visit in previous 3 months) at 3 years post-initiation in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient viral suppression in men and women</measure>
    <time_frame>year 1</time_frame>
    <description>% who are remain virally suppressed (% patients where virus is undetectable) 1 year post-initiation in men and women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient viral suppression in men and women</measure>
    <time_frame>year 3</time_frame>
    <description>% who are remain virally suppressed (% patients where virus is undetectable) 3-years post-initiation in men and women</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">4667</enrollment>
  <condition>HIV</condition>
  <condition>HIV Testing</condition>
  <condition>Linkage to Care</condition>
  <arm_group>
    <arm_group_label>micro-incentives</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>micro-incentives only (8 communities)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EPIC-HIV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Empowered through informed choice for HIV [male sensitive HIV specific decision support app] (males only in 8 communities)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>micro-incentive and EPIC-HIV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>micro-incentives as well as EPIC [male sensitive HIV specific decision support app] (8 communities)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>micro-incentive</intervention_name>
    <description>Residents in these communities are eligible to receive a R50 food voucher conditional on undergoing a home-based HIV test. If diagnosed with HIV, residents are eligible to receive a second R50 food voucher when they link to care within 6 weeks of the HIV test</description>
    <arm_group_label>micro-incentives</arm_group_label>
    <other_name>Food voucher</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>EPIC-HIV</intervention_name>
    <description>Men in these communities are eligible to receive a tablet-based male-sensitive HIV decision support app (EPIC-HIV 1)to encourage them to test for HIV at home. If diagnosed with HIV and do not link to care within a month of HIV test, they become eligible to receive a tablet-based male HIV specific decision support app (EPIC-HIV 2) to encourage them to link to HIV care.</description>
    <arm_group_label>EPIC-HIV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>micro-incentive and EPIC-HIV</intervention_name>
    <description>micro-incentives: Residents in these communities are eligible to receive a R50 food voucher conditional on undergoing a home-based HIV test. If diagnosed with HIV, residents are eligible to receive a second R50 food voucher when they link to care within 6 weeks of the HIV test.&#xD;
EPIC-HIV 1:&#xD;
Men in these communities are eligible to receive a tablet-based male-sensitive HIV specific decision support app (EPIC-HIV 1) to encourage them to test for HIV at home. If diagnosed with HIV and do not link to care within a month of HIV test, they become eligible to receive a tablet-based male HIV specific decision support app (EPIC-HIV 2) to encourage them to link to HIV care.</description>
    <arm_group_label>micro-incentive and EPIC-HIV</arm_group_label>
    <other_name>Food Voucher and EPIC-HIV</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  15 years old and above&#xD;
&#xD;
          -  Resident members of households within the Population Intervention Platform&#xD;
&#xD;
          -  Have consented to participate in Population Intervention Platform&#xD;
&#xD;
        additional eligibility criteria for EPIC-HIV&#xD;
&#xD;
        -Male&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refused to take part in Population Intervention Platform&#xD;
&#xD;
          -  Participant reported to already be on ART&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frank Tanser, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Africa Health Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sashin Harilall</last_name>
    <phone>0312604113</phone>
    <phone_ext>4113</phone_ext>
    <email>sharilall@ahri.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thulile Mathenjwa</last_name>
    <phone>0355507500</phone>
    <phone_ext>7624</phone_ext>
    <email>tmathenjwa@ahri.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>AHRI</name>
      <address>
        <city>Mtubatuba</city>
        <state>KwaZulu Natal</state>
        <zip>3935</zip>
        <country>South Africa</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Frank Tanser, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 27, 2018</last_update_submitted>
  <last_update_submitted_qc>November 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Africa Health Research Institute</investigator_affiliation>
    <investigator_full_name>Frank</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03757104
org study id: A0001-BFC398/16
nct id: NCT03757104
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to establish the causal impact of two interventions - micro-incentives and a
      male-sensitive HIV- specific decision support app - on population-level HIV viral load and
      HIV-related mortality in men, as well as on population-based HIV incidence in young women.
Research aim:

      The primary aim of the home-based intervention to test and start (HITS) trial is to establish
      whether (i) the provision of two micro-incentives and (ii) a male-sensitive and HIV-specific
      decision support app will reduce population-level HIV viral load and HIV-related mortality in
      men, as well as population-level HIV incidence in young women.

      Specific objectives

        1. Establish the causal impact of two micro-incentives (aimed at increasing uptake of
           home-based HIV testing and linkage to care, respectively) on:

             1. Population-level HIV viral load in men

             2. Population-level HIV-related mortality in men

             3. Population-level HIV incidence in young women.

        2. Establish the causal impact of a male-sensitive and HIV-specific decision- support app
           (called EPIC-HIV) on:

             1. Population-level HIV viral load in men

             2. Population-level HIV-related mortality in men

             3. Population-level HIV incidence in young women.

        3. Establish the causal impact of the two conditional micro-incentives on:

             1. HIV status knowledge in men and women

             2. HIV knowledge in men and women

             3. HIV treatment knowledge in men and women

             4. HIV treatment utilization in men and women

             5. Sexual behavior in men and women

             6. Healthcare utilization in men and women

             7. Household healthcare expenditures

             8. Household wealth

             9. Retention in HIV care in men and women

        4. Establish the causal impact of the male-sensitive HIV-specific decision support app on:

             1. HIV status knowledge in men and women

             2. HIV knowledge in men and women

             3. HIV treatment knowledge in men and women

             4. HIV treatment utilization in men and women

             5. Sexual behavior in men and women

             6. Healthcare utilization in men and women

             7. Household healthcare expenditures

             8. Household wealth

             9. Retention in HIV care in men and women

      Hypothesis:

      The investigators hypothesize that each of the two interventions - micro-incentives aimed at
      encouraging HIV testing and linkage to HIV care and a male-sensitive HIV-specific decision
      support app - will each increase HIV testing and HIV treatment uptake and via this mechanism
      lead to reduced population viral load and HIV-related mortality particularly in men. Reduced
      viral load among men, in turn, will reduce HIV incidence in young women.

      Research design Following a formative phase to develop the design of the two HITS
      intervention the investigators will determine the causal impact of the interventions on our
      three primary endpoints in a 2x2 factorial cluster-randomized controlled trial with a
      baseline adjustment. A mixed- methods approach will be employed that combines the strengths
      of rapid formative social science research (that will inform the precise delivery of the HITS
      intervention) with a causally rigorous statistical methodology to evaluate the effectiveness
      of the HITS intervention.

      The HITS intervention will be delivered through the Africa Health Research Institute's (AHRI)
      existing HIV surveillance operations. The investigators will randomize 45 communities to the
      four interventions. 8 communities each will receive one of the interventions
      (micro-incentives only, male-sensitive HIV-specific decision support app only); 8 communities
      will receive both interventions and 21 communities will receive standard-of-care. Communities
      will be stratified by incidence in young women (2004-2016) to derive a similar baseline
      incidence across intervention and standard-of-care communities prior to the implementation of
      the intervention. Both men and women will be eligible to receive the financial incentives to
      test and link to care, whilst only men will be eligible for the EPIC HIV-specific decision
      support application.

      In the total of 3x8=24 communities in the intervention arms, an estimated total of 4,667
      individuals will receive a HITS intervention. In the 21 communities, 4,900 individuals will
      receive the standard-of-care. Outcomes will be assessed in all eligible individuals living in
      the 45 communities, which together have an estimated population size of 30,000 adults.

      Sample size calculation The study was powered using the outcome of HIV incidence in women
      aged 15-30. Using actual Africa Health Research Institute HIV incidence data, the
      investigators simulated the HITS intervention introduced in 2011 to 24 of the 45 communities
      in the study area. The investigators simulated an intervention that led to a 25% reduction in
      arm 1 (micro-incentives), 25% reduction in arm 2 (male-sensitive counselling) and a 32%
      reduction in the combined arm. Communities were stratified by baseline incidence (three
      strata) in young women (2004-2011) to allow for a similar baseline incidence in intervention
      and control communities and the investigators included a random effect in the simulations to
      adjust for clustering by community. The results show that the investigators would have been
      able to detect this reduction in incidence in >80% of simulation replicates (p<0.05).
      Therefore, if the investigators were to introduce the HITS intervention in 2018 and follow
      young women up for at least 3 years post intervention (ie utilize a total of 17 years of
      incidence data - 2004 to 2021) the investigators would be in excess of 90% powered to detect
      such a reduction in incidence in this critical age-group.

      Research methodology Research site:

      The trial will be managed from the Africa Health Research Institute, formerly Africa Centre
      that conducts a large longitudinal Demographic and Health surveillance. Participants will be
      enrolled during the routine HIV surveillance study (Population Intervention Program) -
      trained fieldworkers visit participants at home once a year to conduct household surveys
      using tablet computers and offer point of care HIV testing to all individuals aged 15+.

      Study procedures:

      In those arms of this cluster Randomized Controlled Trial (RCT) that include the once-off
      two-stage micro-incentive scheme, consenting men and women will be offered a first
      opportunity to earn a R50 food voucher (redeemable in a local supermarket) conditional on HIV
      testing. If a participant tests positive for HIV, he/she will have the opportunity to receive
      a second R50 food voucher conditional on linking within 6 weeks following the HIV test to one
      of the 11 local primary care clinics where HIV treatment and care are available.

      In those arms of this cluster RCT that include the male-sensitive HIV-specific decision
      support app, men will be offered EPIC-HIV (a first version, so-called EPIC-HIV-1) prior HIV
      counseling and testing. EPIC-HIV-1 is aimed at increasing HIV testing uptake. Those
      participants who do not link to care within a month of the HIV test will be offered a second
      version of EPIC-HIV (so-called EPIC-HIV-2) at home to encourage linkage to care.

      Follow up of participants:

      Participants will be followed up routinely through the AHRI's ongoing population-based HIV
      surveillance. All participants will be followed up for at least 3 years.

      Linkage to care will be routinely established via the AHRI's ongoing linkage of clinical
      records for all patients in the local public sector ART program in the demographic
      surveillance.

      Data management: Data will be collected and managed by AHRI Research Data Management within
      PIP databases as per AHRI comprehensive study operating procedures (SOPs). The Population
      Intervention Platform (PIP) database has strictly restricted access via a data enclave on a
      secure server.

      Data analysis:

      All primary analyses (of both primary and secondary endpoints) will be intent-to-treat (ITT).

      For the binary primary outcomes - HIV testing uptake, HIV treatment linkage, and
      population-level HIV viral suppression - the investigators will use generalized linear models
      with a Poisson distribution, log link function, and robust error terms to determine effect
      sizes (risk ratios).

      For the two survival-analytical primary endpoints - population-level mortality among men and
      population-level HIV incidence among women - the investigators will use the Cox proportional
      hazards model to determine effect sizes (hazard ratios). If the proportional hazards
      assumption of the Cox model is violated, the investigators will use appropriate alternative
      survival analytical models.

      In all primary analyses, the investigators will adjust for both baseline endpoints and
      clustering. For the survival analytical endpoints, the investigators will use data from the
      period 2004-2017 for baseline endpoint adjustment.

      In addition, to the ITT analyses, the investigators will measure intervention effects
      adjusted for non-compliance using instrumental variable (IV) approaches
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: HIV testing uptake at point of test offer in men
time frame: Baseline
description: % received the rapid HIV test at home among those offered the test in men
measure: HIV treatment linkage at 1 year in men
time frame: year 1
description: % who visited study clinics and initiated antiretroviral therapy (ART) in men
measure: Population-level HIV viral suppression in men
time frame: year 1
description: Change in proportion with detectable viremia in men; HIV testing and viral load measurements are performed on the dried blood spot (DBS) samples collected during the annual survey
measure: Population-level HIV-related mortality in men
time frame: year 3
description: Change in HIV-related mortality rate measured as the number of HIV-related deaths per 1000 person-years of observation in men
measure: Population-level HIV incidence in young women (15-30 years of age)
time frame: year 3
description: Change in HIV incidence rate (number of HIV sero-conversions per 100 person-years of follow up) in young women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: HIV testing uptake at point of test offer in women
time frame: Baseline
description: % received rapid HIV test at home among those offered the test in women
measure: HIV treatment linkage at 1 year in women
time frame: year 1
description: % who visited study clinics and initiated ART in women
measure: Population-level HIV viral suppression (both sexes)
time frame: year 1
description: Change in proportion with detectable viremia in both men and women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: Population-level HIV viral suppression (both sexes)
time frame: year 3
description: Change in proportion with detectable viremia in both men and women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: Population-level HIV viral suppression in women
time frame: year 1
description: Change in proportion with detectable viremia in women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: Population-level HIV viral suppression in women
time frame: year 3
description: Change in proportion with detectable viremia in women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: Population-level HIV viral suppression in men
time frame: year 3
description: Change in proportion with detectable viremia in men; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: Population level HIV incidence (both sexes)
time frame: year 3
description: Change in HIV incidence rate (number of HIV sero-conversions per 100 person-years of follow up) in both men and women; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: Population-level HIV-related mortality (both sexes)
time frame: year 3
description: Change in HIV-related mortality rate measured as the number of HIV-related deaths per 1000 person-years of observation in both men and women
measure: Population-level all-cause mortality (both sexes)
time frame: year 3
description: Change in all-cause mortality rate measured as the number of all-cause deaths per 1000 person-years of observation in both men and women
measure: Population-level HIV-related mortality in women
time frame: year 3
description: Change in HIV-related mortality rate measured as the number of HIV-related deaths per 1000 person-years of observation in women
measure: Population-level HIV incidence in men
time frame: year 3
description: Change in HIV incidence rate (number of HIV sero-conversions per 100 person-years of follow up) in men; HIV testing and viral load measurements are performed on the DBS samples collected during the annual survey
measure: HIV status knowledge in men and women
time frame: year 1
description: % ever received a test result for HIV in men and women
measure: HIV prevention knowledge in men and women
time frame: year 1
description: % reporting ever hearing about pre-exposure prophylaxis (PrEP)
measure: HIV treatment utilization in men and women
time frame: year 1
description: % reporting ever taking up ART for own health in men and women
measure: Reported condom use in men and women
time frame: year 1
description: % reporting condom use at last sex in men and women
measure: Tuberculosis (TB) healthcare utilization in men and women
time frame: year 1
description: % reported starting TB treatment in the past 12 months in men and women
measure: Diabetes Healthcare utilization in men and women
time frame: year 1
description: % reported starting diabetes treatment in the past 12 months
measure: Hypertension healthcare utilization in men and women
time frame: year 1
description: % reported starting blood pressure treatment in the past 12 months in men and women
measure: Household wealth (household assets)
time frame: year 3
description: Number of household assets (selected from a predefined list of 32 assets)
measure: Household wealth (food security)
time frame: year 3
description: % of adults in the household ever cutting the size of meals or missing meals due to insufficient money for food in the past 12 months
measure: Partnership patterns in men and women
time frame: year 1
description: % reporting having more than one sexual partner in the past 12 months in men and women
measure: Retention in HIV care in men and women
time frame: year 1
description: % who are retained in care (% patients having an ART clinic visit in previous 3 months) at 1 year post-initiation in men and women
measure: Retention in HIV care in men and women
time frame: year 3
description: % who are retained in care (% patients having an ART clinic visit in previous 3 months) at 3 years post-initiation in men and women
measure: Patient viral suppression in men and women
time frame: year 1
description: % who are remain virally suppressed (% patients where virus is undetectable) 1 year post-initiation in men and women
measure: Patient viral suppression in men and women
time frame: year 3
description: % who are remain virally suppressed (% patients where virus is undetectable) 3-years post-initiation in men and women
arm group label: micro-incentives
arm group type: Experimental
description: micro-incentives only (8 communities)
arm group label: EPIC-HIV
arm group type: Experimental
description: Empowered through informed choice for HIV [male sensitive HIV specific decision support app] (males only in 8 communities)
arm group label: micro-incentive and EPIC-HIV
arm group type: Experimental
description: micro-incentives as well as EPIC [male sensitive HIV specific decision support app] (8 communities)
arm group label: control
arm group type: No Intervention
description: standard of care
intervention type: Behavioral
intervention name: micro-incentive
description: Residents in these communities are eligible to receive a R50 food voucher conditional on undergoing a home-based HIV test. If diagnosed with HIV, residents are eligible to receive a second R50 food voucher when they link to care within 6 weeks of the HIV test
arm group label: micro-incentives
other name: Food voucher
intervention type: Behavioral
intervention name: EPIC-HIV
description: Men in these communities are eligible to receive a tablet-based male-sensitive HIV decision support app (EPIC-HIV 1)to encourage them to test for HIV at home. If diagnosed with HIV and do not link to care within a month of HIV test, they become eligible to receive a tablet-based male HIV specific decision support app (EPIC-HIV 2) to encourage them to link to HIV care.
arm group label: EPIC-HIV
intervention type: Behavioral
intervention name: micro-incentive and EPIC-HIV
description: micro-incentives: Residents in these communities are eligible to receive a R50 food voucher conditional on undergoing a home-based HIV test. If diagnosed with HIV, residents are eligible to receive a second R50 food voucher when they link to care within 6 weeks of the HIV test.
EPIC-HIV 1:
Men in these communities are eligible to receive a tablet-based male-sensitive HIV specific decision support app (EPIC-HIV 1) to encourage them to test for HIV at home. If diagnosed with HIV and do not link to care within a month of HIV test, they become eligible to receive a tablet-based male HIV specific decision support app (EPIC-HIV 2) to encourage them to link to HIV care.
arm group label: micro-incentive and EPIC-HIV
other name: Food Voucher and EPIC-HIV
criteria: 
gender: All
minimum age: 15 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Frank Tanser, PhD
role: Principal Investigator
affiliation: Africa Health Research Institute
last name: Sashin Harilall
phone: 0312604113
phone ext: 4113
email: sharilall@ahri.org
last name: Thulile Mathenjwa
phone: 0355507500
phone ext: 7624
email: tmathenjwa@ahri.org
facility: 
status: Recruiting
investigator: 
country: South Africa
responsible party type: Principal Investigator
investigator affiliation: Africa Health Research Institute
investigator full name: Frank
investigator title: Professor
sharing ipd: Undecided