<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/NCT03242980</url>
  </required_header>
  <id_info>
    <org_study_id>SAVIR</org_study_id>
    <nct_id>NCT03242980</nct_id>
  </id_info>
  <brief_title>Short Adherence Intervention for Viral Re-suppression</brief_title>
  <acronym>SAVIR</acronym>
  <official_title>Short Adherence Intervention for Viral Re-suppression (SAVIR) Study: A Stepped Wedge Randomized Controlled Study to Assess the Effect of Standardized Adherence Counselling in Individuals With Unsuppressed Viral Load in Lesotho</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Swiss Tropical &amp; Public Health Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SolidarMed</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ministry of Health, Lesotho</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Basel</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Swiss Tropical &amp; Public Health 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>
      In the era of test-and-treat, with anticipated high numbers of patients who will have&#xD;
      unsuppressed viral load (VL) due to poor adherence, simple, short and standardized adherence&#xD;
      interventions with documented efficacy will be needed. Achieving re-suppression in patients&#xD;
      with unsuppressed VL is beneficial for the health of the individual, important to reduce the&#xD;
      risk of transmission and has a direct cost implication because patients with sustained&#xD;
      unsuppressed VL will ultimately be switched to more expensive 2nd-line regimens.&#xD;
&#xD;
      Information is still largely lacking on how to best address adherence problems among patients&#xD;
      with unsuppressed VL. VL monitoring is recognized as a useful tool to reinforce adherence in&#xD;
      patients with unsuppressed VL. The Lesotho Guidelines recommend redoing a VL 8-12 weeks after&#xD;
      the first enhanced adherence counselling. To date no study has been published clearly&#xD;
      demonstrating higher re-suppression rates after enhanced adherence counselling for patients&#xD;
      with unsuppressed VL.&#xD;
&#xD;
      This project aims to test an adherence intervention for HIV-positive individuals on&#xD;
      first-line ART who have an unsuppressed viral load. A step wedged study will be used to&#xD;
      compare the effectiveness of a short, standardized adherence counselling followed by an SMS&#xD;
      reminder to the standard of care (≥ 2 unstructured adherence counselling sessions) in terms&#xD;
      of viral re-suppression rates and switches to 2nd line ART.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to a lack of routine viral load (VL) monitoring in Lesotho until now, most health care&#xD;
      workers in the districts lack the necessary information on how to manage patients with&#xD;
      elevated viral loads. The CART-1 study found re-suppression rates of only 30% with only 70%&#xD;
      returning for a second VL. From these estimates, it is clear that the current practice for&#xD;
      managing these patients must be improved. A simple intervention has been designed that could&#xD;
      be feasibly adapted at all health centres in Lesotho.&#xD;
&#xD;
      To ensure that the effect of this intervention is measured and to avoid a long delay in&#xD;
      adopting the intervention, a stepped wedge design was chosen. In addition the study would&#xD;
      thus not disrupt the on-going staggered roll-out of routine viral load provision to patients&#xD;
      on ART at the 12 health facilities. Stepped wedge designs are a form of clustered study in&#xD;
      which the intervention is delivered to groups rather than individuals. In this case, the&#xD;
      cluster is the hospital or health centre. Each health centre will undergo a time period with&#xD;
      the standard of care and then will be randomly selected to cross-over to the intervention at&#xD;
      different time points, until all of the health centres have crossed-over to receive the&#xD;
      intervention. Data on the endpoint will be collected continuously at all health centres. The&#xD;
      use of a step wedged study is pragmatic - the intervention is offered to exert its expected&#xD;
      benefits and research insight is a secondary aim. This innovative design will lead to much&#xD;
      stronger evidence than observational studies.&#xD;
&#xD;
      Routine VL (viral load) monitoring started in Butha-Buthe hospital in December 2015, in&#xD;
      Seboche Hospital in May 2016 and the remaining 10 health centres in June 2016. Once each&#xD;
      hospital/health center has implemented routine VL monitoring for a least 12 weeks, the&#xD;
      standardized adherence intervention will be rolled out to the hospitals/health centers in a&#xD;
      randomized fashion. Every 12 weeks starting in May 2017, two hospitals/health centers will be&#xD;
      randomly selected to start with the adherence intervention.&#xD;
&#xD;
      Randomization times will be separated by 12 weeks to allow for implementation and assessment&#xD;
      of the intervention within each time period. Final data collection will occur in October&#xD;
      2018. All nurses at the centres will be trained in the standardized adherence counselling by&#xD;
      an experienced professional counselor and an experienced ART nurse prior to the introduction&#xD;
      of the intervention.&#xD;
&#xD;
      The tracing of patients who do not show up for adherence counselling sessions or confirmatory&#xD;
      VL will be done according to the current system in use at the health centre (usually contact&#xD;
      individual via village health worker or phone if available) and will remain the same during&#xD;
      both the control and intervention period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 18, 2017</start_date>
  <completion_date type="Actual">December 1, 2019</completion_date>
  <primary_completion_date type="Actual">August 1, 2019</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>Sequential Assignment</intervention_model>
    <intervention_model_description>To ensure that the effect of this intervention is measured and to avoid a long delay in adopting the intervention, a stepped wedge design was chosen. In addition the study would thus not disrupt the on-going staggered roll-out of routine viral load provision to patients on ART at the 12 health facilities. Stepped wedge designs are a form of clustered study in which the intervention is delivered to groups rather than individuals.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Re-suppression rates after one elevated viral load</measure>
    <time_frame>Up to 16 weeks</time_frame>
    <description>HIV viral load &lt;1000 copies/ml</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rates of switch to second-line ART</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Any switch to protease-inhibitor based ART</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major drug resistance mutations</measure>
    <time_frame>3 months after 1st elevated VL</time_frame>
    <description>Presence of any major drug resistance mutation in those with 2nd elevated VL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of attrition from care</measure>
    <time_frame>6 months</time_frame>
    <description>No attendance at the clinic within 6 months after informing the patient about his/her first elevated VL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of viral re-suppression</measure>
    <time_frame>6 months after switch</time_frame>
    <description>In those who switched to 2nd line</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">928</enrollment>
  <condition>Adherence, Medication</condition>
  <condition>HIV/AIDS</condition>
  <arm_group>
    <arm_group_label>Enhanced adherence counseling</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Individuals with elevated VL are required to attend a minimum of 2 session of enhanced adherence counselling performed at monthly intervals. A follow-up VL is done at 8 to 12 weeks after the first counselling session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Structured EAC plus SMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The behavioral intervention will consist of structured adherence counseling and a short text message (SMS). A culturally adapted graphical brochure was specifically developed to guide adherence-counselling for individuals with unsuppressed VL.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Structured adherence counseling</intervention_name>
    <description>Patients will undergo one standardized enhanced adherence counselling session. Counselling guidelines and a brochure were specifically developed to guide the adherence counselling for individuals with unsuppressed VL. All nurses at the health centres will be trained on the counselling prior to the cross-over to the intervention. The brochure was developed by culturally adapted by social scientists and contains only 3 key messages. The brochure will be given to the patient to take home.&#xD;
Four weeks after the adherence counselling session, a SMS will be sent to the patient reminding them to take their ART. The content of the text message will be anonymous to protect disclosure and discussed/agreed upon with the patient during the adherence counselling.</description>
    <arm_group_label>Structured EAC plus SMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients receiving VL monitoring at one of the 2 hospitals and 10 health centres&#xD;
             in Butha-Buthe district&#xD;
&#xD;
          -  Patients on first-line ART&#xD;
&#xD;
          -  Patients with a VL≥ 1000 copies/mL after a minimum of 6 months on first-line ART&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving VL monitoring at a non-participating center in Butha-Buthe&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tracy R Glass, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Swiss TPH</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Niklaus Labhardt, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Swiss TPH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boiketsiso Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linakeng Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Makhunoane Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Motete Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Muela Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ngoajane Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Paballong</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rampai Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seboche</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Paul Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Peters Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tsime Health Center</name>
      <address>
        <city>Butha-Buthe</city>
        <country>Lesotho</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lesotho</country>
  </location_countries>
  <reference>
    <citation>Government of Lesotho: NATIONAL GUIDELINES ON THE USE OF ANTIRETROVIRAL THERAPY FOR HIV PREVENTION AND TREATMENT. Fifth Edition 2016.</citation>
  </reference>
  <reference>
    <citation>Conway B. The role of adherence to antiretroviral therapy in the management of HIV infection. J Acquir Immune Defic Syndr. 2007 Jun 1;45 Suppl 1:S14-8. doi: 10.1097/QAI.0b013e3180600766.</citation>
    <PMID>17525686</PMID>
  </reference>
  <reference>
    <citation>Bonner K, Mezochow A, Roberts T, Ford N, Cohn J. Viral load monitoring as a tool to reinforce adherence: a systematic review. J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):74-8. doi: 10.1097/QAI.0b013e31829f05ac.</citation>
    <PMID>23774877</PMID>
  </reference>
  <reference>
    <citation>Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Kershberger B, Khogali M, Lujan J, Antierens A, Teck R, Ellman T, Kosgei R, Reid T. Factors associated with virological failure and suppression after enhanced adherence counselling, in children, adolescents and adults on antiretroviral therapy for HIV in Swaziland. PLoS One. 2015 Feb 19;10(2):e0116144. doi: 10.1371/journal.pone.0116144. eCollection 2015.</citation>
    <PMID>25695494</PMID>
  </reference>
  <reference>
    <citation>Ministry of Health and Social Welfare Lesotho: National Guidelines For HIV Testing And Counselling. National Guidelines For HIV Testing And Counselling 2009.</citation>
  </reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>December 16, 2019</last_update_submitted>
  <last_update_submitted_qc>December 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Swiss Tropical &amp; Public Health Institute</investigator_affiliation>
    <investigator_full_name>Tracy Glass</investigator_full_name>
    <investigator_title>Project Leader</investigator_title>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>Adherence</keyword>
  <keyword>Viral re-suppression</keyword>
  <keyword>Step-wedgged randomized trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03242980
org study id: SAVIR
nct id: NCT03242980
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In the era of test-and-treat, with anticipated high numbers of patients who will have
      unsuppressed viral load (VL) due to poor adherence, simple, short and standardized adherence
      interventions with documented efficacy will be needed. Achieving re-suppression in patients
      with unsuppressed VL is beneficial for the health of the individual, important to reduce the
      risk of transmission and has a direct cost implication because patients with sustained
      unsuppressed VL will ultimately be switched to more expensive 2nd-line regimens.

      Information is still largely lacking on how to best address adherence problems among patients
      with unsuppressed VL. VL monitoring is recognized as a useful tool to reinforce adherence in
      patients with unsuppressed VL. The Lesotho Guidelines recommend redoing a VL 8-12 weeks after
      the first enhanced adherence counselling. To date no study has been published clearly
      demonstrating higher re-suppression rates after enhanced adherence counselling for patients
      with unsuppressed VL.

      This project aims to test an adherence intervention for HIV-positive individuals on
      first-line ART who have an unsuppressed viral load. A step wedged study will be used to
      compare the effectiveness of a short, standardized adherence counselling followed by an SMS
      reminder to the standard of care (≥ 2 unstructured adherence counselling sessions) in terms
      of viral re-suppression rates and switches to 2nd line ART.
Due to a lack of routine viral load (VL) monitoring in Lesotho until now, most health care
      workers in the districts lack the necessary information on how to manage patients with
      elevated viral loads. The CART-1 study found re-suppression rates of only 30% with only 70%
      returning for a second VL. From these estimates, it is clear that the current practice for
      managing these patients must be improved. A simple intervention has been designed that could
      be feasibly adapted at all health centres in Lesotho.

      To ensure that the effect of this intervention is measured and to avoid a long delay in
      adopting the intervention, a stepped wedge design was chosen. In addition the study would
      thus not disrupt the on-going staggered roll-out of routine viral load provision to patients
      on ART at the 12 health facilities. Stepped wedge designs are a form of clustered study in
      which the intervention is delivered to groups rather than individuals. In this case, the
      cluster is the hospital or health centre. Each health centre will undergo a time period with
      the standard of care and then will be randomly selected to cross-over to the intervention at
      different time points, until all of the health centres have crossed-over to receive the
      intervention. Data on the endpoint will be collected continuously at all health centres. The
      use of a step wedged study is pragmatic - the intervention is offered to exert its expected
      benefits and research insight is a secondary aim. This innovative design will lead to much
      stronger evidence than observational studies.

      Routine VL (viral load) monitoring started in Butha-Buthe hospital in December 2015, in
      Seboche Hospital in May 2016 and the remaining 10 health centres in June 2016. Once each
      hospital/health center has implemented routine VL monitoring for a least 12 weeks, the
      standardized adherence intervention will be rolled out to the hospitals/health centers in a
      randomized fashion. Every 12 weeks starting in May 2017, two hospitals/health centers will be
      randomly selected to start with the adherence intervention.

      Randomization times will be separated by 12 weeks to allow for implementation and assessment
      of the intervention within each time period. Final data collection will occur in October
      2018. All nurses at the centres will be trained in the standardized adherence counselling by
      an experienced professional counselor and an experienced ART nurse prior to the introduction
      of the intervention.

      The tracing of patients who do not show up for adherence counselling sessions or confirmatory
      VL will be done according to the current system in use at the health centre (usually contact
      individual via village health worker or phone if available) and will remain the same during
      both the control and intervention period.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: To ensure that the effect of this intervention is measured and to avoid a long delay in adopting the intervention, a stepped wedge design was chosen. In addition the study would thus not disrupt the on-going staggered roll-out of routine viral load provision to patients on ART at the 12 health facilities. Stepped wedge designs are a form of clustered study in which the intervention is delivered to groups rather than individuals.
primary purpose: Health Services Research
masking: None (Open Label)
measure: Re-suppression rates after one elevated viral load
time frame: Up to 16 weeks
description: HIV viral load <1000 copies/ml
measure: Rates of switch to second-line ART
time frame: Up to 6 months
description: Any switch to protease-inhibitor based ART
measure: Major drug resistance mutations
time frame: 3 months after 1st elevated VL
description: Presence of any major drug resistance mutation in those with 2nd elevated VL
measure: Rates of attrition from care
time frame: 6 months
description: No attendance at the clinic within 6 months after informing the patient about his/her first elevated VL
measure: Rates of viral re-suppression
time frame: 6 months after switch
description: In those who switched to 2nd line
arm group label: Enhanced adherence counseling
arm group type: No Intervention
description: Individuals with elevated VL are required to attend a minimum of 2 session of enhanced adherence counselling performed at monthly intervals. A follow-up VL is done at 8 to 12 weeks after the first counselling session.
arm group label: Structured EAC plus SMS
arm group type: Experimental
description: The behavioral intervention will consist of structured adherence counseling and a short text message (SMS). A culturally adapted graphical brochure was specifically developed to guide adherence-counselling for individuals with unsuppressed VL.
intervention type: Behavioral
intervention name: Structured adherence counseling
description: Patients will undergo one standardized enhanced adherence counselling session. Counselling guidelines and a brochure were specifically developed to guide the adherence counselling for individuals with unsuppressed VL. All nurses at the health centres will be trained on the counselling prior to the cross-over to the intervention. The brochure was developed by culturally adapted by social scientists and contains only 3 key messages. The brochure will be given to the patient to take home.
Four weeks after the adherence counselling session, a SMS will be sent to the patient reminding them to take their ART. The content of the text message will be anonymous to protect disclosure and discussed/agreed upon with the patient during the adherence counselling.
arm group label: Structured EAC plus SMS
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Tracy R Glass, PhD
role: Principal Investigator
affiliation: Swiss TPH
last name: Niklaus Labhardt, MD
role: Study Chair
affiliation: Swiss TPH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Lesotho
citation: Government of Lesotho: NATIONAL GUIDELINES ON THE USE OF ANTIRETROVIRAL THERAPY FOR HIV PREVENTION AND TREATMENT. Fifth Edition 2016.
citation: Conway B. The role of adherence to antiretroviral therapy in the management of HIV infection. J Acquir Immune Defic Syndr. 2007 Jun 1;45 Suppl 1:S14-8. doi: 10.1097/QAI.0b013e3180600766.
PMID: 17525686
citation: Bonner K, Mezochow A, Roberts T, Ford N, Cohn J. Viral load monitoring as a tool to reinforce adherence: a systematic review. J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):74-8. doi: 10.1097/QAI.0b013e31829f05ac.
PMID: 23774877
citation: Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Kershberger B, Khogali M, Lujan J, Antierens A, Teck R, Ellman T, Kosgei R, Reid T. Factors associated with virological failure and suppression after enhanced adherence counselling, in children, adolescents and adults on antiretroviral therapy for HIV in Swaziland. PLoS One. 2015 Feb 19;10(2):e0116144. doi: 10.1371/journal.pone.0116144. eCollection 2015.
PMID: 25695494
citation: Ministry of Health and Social Welfare Lesotho: National Guidelines For HIV Testing And Counselling. National Guidelines For HIV Testing And Counselling 2009.
responsible party type: Principal Investigator
investigator affiliation: Swiss Tropical & Public Health Institute
investigator full name: Tracy Glass
investigator title: Project Leader
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
sharing ipd: No