<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/NCT04491422</url>
  </required_header>
  <id_info>
    <org_study_id>REC REF 0105-2020</org_study_id>
    <nct_id>NCT04491422</nct_id>
  </id_info>
  <brief_title>Same-Day PrEP Initiation and Sexual Health for Transgender Women</brief_title>
  <official_title>Same-Day PrEP Initiation and Sexual Health for Transgender Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Makerere University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Harvard Medical School (HMS and HSDM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Makerere University</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>
      Transgender women (trans women; assigned male sex at birth but identify as female) are at&#xD;
      high risk for HIV infection, and are an important, under-researched population in sub-Saharan&#xD;
      Africa. Trans women have a 13 times greater risk of acquiring HIV than adults aged 15-49&#xD;
      years in the general population, and in Africa, trans women have nearly twice the HIV&#xD;
      prevalence (25%) of men who have sex with men [MSM] (14%). Oral pre-exposure prophylaxis&#xD;
      (PrEP) is an effective prevention tool that could change the trajectory of the HIV epidemic&#xD;
      among the 25 million trans women globally, yet its use has been suboptimal in this vulnerable&#xD;
      population. Same-day PrEP initiation is feasible and acceptable and improves retention in&#xD;
      PrEP care in resource-rich settings. Same-day initiation of emtricitabine/tenofovir&#xD;
      alafenamide (F/TAF), a new PrEP regimen, has not to our knowledge previously been evaluated&#xD;
      as PrEP in African trans women. F/TAF is potentially more efficacious and safer than&#xD;
      emtricitabine/tenofovir disoproxil fumarate (F/TDF) as shown in the recent DISCOVER trial.&#xD;
      However, concerns about drug-drug interactions between feminizing hormonal therapy (FHT) and&#xD;
      PrEP are a key potential adherence barrier for trans women. While PrEP drugs do not lower FHT&#xD;
      levels, FHT decreases plasma TFV and (emtricitabine) FTC levels. Little is known about FHT&#xD;
      use among African trans women taking F/TAF or how concerns about F/TAF-FHT interactions may&#xD;
      influence PrEP adherence. Moreover, interventions to support PrEP adherence in this&#xD;
      population are needed. Feedback about PrEP use has been shown to potentially improve PrEP&#xD;
      adherence among MSM but has not been utilized among trans women. Key knowledge gaps include:&#xD;
      1) whether same-day PrEP can be successfully implemented for African trans women, 2) the&#xD;
      impact of drug-level feedback on PrEP adherence, and 3) how use of FHT may influence PrEP&#xD;
      adherence.&#xD;
&#xD;
      To address these questions, this protocol describes a randomized trial to evaluate the&#xD;
      feasibility and acceptability of same day initiation of F/TAF PrEP, evaluate impact of&#xD;
      drug-level feedback on PrEP adherence and characterize PrEP persistence, and in-depth&#xD;
      interviews to explore how self-care interventions for sexual health influence prevention&#xD;
      choices among trans women and their sexual partners. This will be the first clinical trial,&#xD;
      to our knowledge, to evaluate F/TAF as PrEP for HIV-negative trans women in sub-Saharan&#xD;
      Africa.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall goal of this study is to evaluate the feasibility and acceptability of same-day&#xD;
      F/TAF initiation and characterize F/TAF persistence among trans women taking PrEP. This&#xD;
      research will be conducted at the Infectious Diseases Institute, Makerere University in&#xD;
      Kampala, Uganda and consists of 3 complementary aims. In Aims 1 and 2, the investigators will&#xD;
      assess the feasibility and acceptability of same-day F/TAF initiation and characterize PrEP&#xD;
      persistence. In Aim 3, the investigators will use qualitative methods to explore how&#xD;
      self-care interventions for sexual health influence prevention choices among trans women and&#xD;
      their sexual partners. Study subjects will be accrued using respondent driven sampling (RDS)&#xD;
      and enrolled at the study clinic where F/TAF will be initiated same day. Participants will be&#xD;
      randomized in a 1:1 ratio to either the intervention arm (quarterly integrated next steps&#xD;
      counseling [iNSC] using point-of-care [POC] urine tenofovir [TFV] levels) or the control arm&#xD;
      (standard adherence counseling without drug level feedback). In Aim 3, the investigators will&#xD;
      use qualitative methods to explore how self-care interventions for sexual health influence&#xD;
      prevention choices among trans women and their sexual partners. The overall goal will be to&#xD;
      assess whether POC urine testing and iNSC counseling increase PrEP uptake and persistence&#xD;
      over 12 months. This study for trans women is guided by the cardinal ethical principles of&#xD;
      justice, respect for persons and beneficence. The local trans community will be involved in&#xD;
      study design and implementation.&#xD;
&#xD;
      Aim 1 : Evaluate the feasibility and acceptability of same-day F/TAF PrEP initiation among&#xD;
      African trans women.&#xD;
&#xD;
      Approach: The investigators will recruit up to 200 trans women. All study participants who&#xD;
      meet study eligibility criteria will be consented and enrolled at the study clinic.&#xD;
      Randomization will occur through REDCap. Participants will start PrEP on the day of&#xD;
      enrollment and receive F/TAF for 12 months. Free HIV and sexually transmitted infection (STI)&#xD;
      testing and treatment will be provided to all participants.&#xD;
&#xD;
      Aim 2 : Characterize F/TAF persistence and test the impact of drug level feedback among&#xD;
      African trans women taking PrEP.&#xD;
&#xD;
      Approach: Using a factorial design within the Aim 1 study, all F/TAF users will be randomized&#xD;
      to real-time drug level feedback and adherence counseling using a POC urine TFV lateral-flow&#xD;
      immunoassay versus standard counseling alone. Socio-behavioral surveys will assess potential&#xD;
      factors influencing adherence, including gender dysphoria and FHT.&#xD;
&#xD;
      Aim 3 : Explore how self-care interventions for sexual health influence HIV/STI prevention&#xD;
      choices among African trans women and their sexual partners.&#xD;
&#xD;
      Approach: To clarify how same-day PrEP initiation, FHT use and self-collection of samples&#xD;
      (SCS) for STI testing may influence prevention choices, the investigators will conduct&#xD;
      in-depth interviews with participants and their sexual partners to assess perceptions and&#xD;
      experiences with same-day PrEP, real-time drug level feedback, use of FHT, SCS, and how&#xD;
      self-care interventions could empower trans women to engage in prevention services.&#xD;
&#xD;
      Hypothesis: Same-day PrEP initiation will be a feasible and acceptable entryway into PrEP&#xD;
      care among trans women.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 2, 2021</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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>Participants will be randomized in a 1:1 ratio to either quarterly Integrated Next Steps Counseling (iNSC) using point-of-care (POC) urine tenofovir (TFV) levels [intervention arm] or standard adherence counseling without drug level feedback [control arm].</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of same-day initiation of F/TAF as PrEP as measured by participant engagement until the end of study</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion retained on PrEP at months 3, 6, 9 and 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acceptability of peer-delivered combination HIV prevention as measured by the System Usability Scale</measure>
    <time_frame>12 months</time_frame>
    <description>System Usability Scale scores range from 0 to 100; higher scores mean better acceptability</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adoption of same-day PrEP initiation as measured by structured questionnaires</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion initiating same-day PrEP at enrollment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fidelity to iNSC assessed through audio-recorded drug level feedback counseling sessions</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of research nurses successfully implementing iNSC</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PrEP persistence as measured by intracellular tenofovir diphosphate levels in dried blood spots at months 3, 6, 9, 12</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion with tenofovir diphosphate levels &gt;900 fmol per punch</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sexual risk behaviors assessed through structured questionnaires</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion reporting unprotected sex, sexual frequency</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>STI incidence assessed through GeneXpert testing</measure>
    <time_frame>12 months</time_frame>
    <description>Neisseria gonorrhoeae and Chlamydia trachomatis incidence</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>HIV</condition>
  <condition>PrEP</condition>
  <condition>Transgender Women</condition>
  <condition>Sexually Transmitted Diseases, Bacterial</condition>
  <arm_group>
    <arm_group_label>Integrated Next Steps Counseling using poi</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>At quarterly visits, intervention arm participants will receive iNSC Support Level 1 to address PrEP adherence and sexual health needs. Those with urine TFV levels &lt;1000 ng/mL will receive iNSC Support Level 2, in which participant responses to two 7-item questionnaires on PrEP adherence and sexual health will guide problem solving on improved dosing.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard adherence counseling</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control arm participants will receive standard adherence counseling.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Integrated Next Steps Counseling with Real-Time Drug Level Feedback</intervention_name>
    <description>Integrated next steps counseling with real-time drug level feedback using point-of-care urine tenofovir testing at quarterly visits</description>
    <arm_group_label>Integrated Next Steps Counseling using poi</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Report male sex assigned at birth but currently identify as female&#xD;
&#xD;
          -  Age ≥18, or if 14-17 years, qualification as a mature or emancipated minor due to&#xD;
             having a sexually transmitted infection or cater for own livelihood&#xD;
&#xD;
          -  Report unprotected anal intercourse in the past 6 months&#xD;
&#xD;
          -  Able and willing to provide written informed consent&#xD;
&#xD;
          -  Possess a valid recruitment coupon&#xD;
&#xD;
          -  HIV-uninfected based on negative HIV rapid tests at the enrollment visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently enrolled in a biomedical HIV prevention study&#xD;
&#xD;
          -  Any clinically significant or chronic medical condition that is considered progressive&#xD;
             or in the opinion of the investigator would make the participant unsuitable for the&#xD;
             study, including severe infections requiring treatment such as tuberculosis, alcohol&#xD;
             or drug abuse, or mental illness which precludes provision of informed consent&#xD;
&#xD;
          -  Not planning to remain in the geographic area for the duration of the study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Self-identify as transgender women</gender_description>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Mujugira, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Infectious Diseases Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Andrew Mujugira, PhD</last_name>
    <phone>+256 754 173 225</phone>
    <email>amujugira@idi.co.ug</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yvonne Kamara, BA</last_name>
    <phone>+256 777 008 598</phone>
    <email>ykamara@idi.co.ug</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Infectious Diseases Institute Kasangati</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Miriam Nampala, MA</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Uganda</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>December 2, 2021</last_update_submitted>
  <last_update_submitted_qc>December 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sexually Transmitted Diseases</mesh_term>
    <mesh_term>Sexually Transmitted Diseases, Bacterial</mesh_term>
  </condition_browse>
  <!-- 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/NCT04491422
org study id: REC REF 0105-2020
nct id: NCT04491422
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
Transgender women (trans women; assigned male sex at birth but identify as female) are at
      high risk for HIV infection, and are an important, under-researched population in sub-Saharan
      Africa. Trans women have a 13 times greater risk of acquiring HIV than adults aged 15-49
      years in the general population, and in Africa, trans women have nearly twice the HIV
      prevalence (25%) of men who have sex with men [MSM] (14%). Oral pre-exposure prophylaxis
      (PrEP) is an effective prevention tool that could change the trajectory of the HIV epidemic
      among the 25 million trans women globally, yet its use has been suboptimal in this vulnerable
      population. Same-day PrEP initiation is feasible and acceptable and improves retention in
      PrEP care in resource-rich settings. Same-day initiation of emtricitabine/tenofovir
      alafenamide (F/TAF), a new PrEP regimen, has not to our knowledge previously been evaluated
      as PrEP in African trans women. F/TAF is potentially more efficacious and safer than
      emtricitabine/tenofovir disoproxil fumarate (F/TDF) as shown in the recent DISCOVER trial.
      However, concerns about drug-drug interactions between feminizing hormonal therapy (FHT) and
      PrEP are a key potential adherence barrier for trans women. While PrEP drugs do not lower FHT
      levels, FHT decreases plasma TFV and (emtricitabine) FTC levels. Little is known about FHT
      use among African trans women taking F/TAF or how concerns about F/TAF-FHT interactions may
      influence PrEP adherence. Moreover, interventions to support PrEP adherence in this
      population are needed. Feedback about PrEP use has been shown to potentially improve PrEP
      adherence among MSM but has not been utilized among trans women. Key knowledge gaps include:
      1) whether same-day PrEP can be successfully implemented for African trans women, 2) the
      impact of drug-level feedback on PrEP adherence, and 3) how use of FHT may influence PrEP
      adherence.

      To address these questions, this protocol describes a randomized trial to evaluate the
      feasibility and acceptability of same day initiation of F/TAF PrEP, evaluate impact of
      drug-level feedback on PrEP adherence and characterize PrEP persistence, and in-depth
      interviews to explore how self-care interventions for sexual health influence prevention
      choices among trans women and their sexual partners. This will be the first clinical trial,
      to our knowledge, to evaluate F/TAF as PrEP for HIV-negative trans women in sub-Saharan
      Africa.
The overall goal of this study is to evaluate the feasibility and acceptability of same-day
      F/TAF initiation and characterize F/TAF persistence among trans women taking PrEP. This
      research will be conducted at the Infectious Diseases Institute, Makerere University in
      Kampala, Uganda and consists of 3 complementary aims. In Aims 1 and 2, the investigators will
      assess the feasibility and acceptability of same-day F/TAF initiation and characterize PrEP
      persistence. In Aim 3, the investigators will use qualitative methods to explore how
      self-care interventions for sexual health influence prevention choices among trans women and
      their sexual partners. Study subjects will be accrued using respondent driven sampling (RDS)
      and enrolled at the study clinic where F/TAF will be initiated same day. Participants will be
      randomized in a 1:1 ratio to either the intervention arm (quarterly integrated next steps
      counseling [iNSC] using point-of-care [POC] urine tenofovir [TFV] levels) or the control arm
      (standard adherence counseling without drug level feedback). In Aim 3, the investigators will
      use qualitative methods to explore how self-care interventions for sexual health influence
      prevention choices among trans women and their sexual partners. The overall goal will be to
      assess whether POC urine testing and iNSC counseling increase PrEP uptake and persistence
      over 12 months. This study for trans women is guided by the cardinal ethical principles of
      justice, respect for persons and beneficence. The local trans community will be involved in
      study design and implementation.

      Aim 1 : Evaluate the feasibility and acceptability of same-day F/TAF PrEP initiation among
      African trans women.

      Approach: The investigators will recruit up to 200 trans women. All study participants who
      meet study eligibility criteria will be consented and enrolled at the study clinic.
      Randomization will occur through REDCap. Participants will start PrEP on the day of
      enrollment and receive F/TAF for 12 months. Free HIV and sexually transmitted infection (STI)
      testing and treatment will be provided to all participants.

      Aim 2 : Characterize F/TAF persistence and test the impact of drug level feedback among
      African trans women taking PrEP.

      Approach: Using a factorial design within the Aim 1 study, all F/TAF users will be randomized
      to real-time drug level feedback and adherence counseling using a POC urine TFV lateral-flow
      immunoassay versus standard counseling alone. Socio-behavioral surveys will assess potential
      factors influencing adherence, including gender dysphoria and FHT.

      Aim 3 : Explore how self-care interventions for sexual health influence HIV/STI prevention
      choices among African trans women and their sexual partners.

      Approach: To clarify how same-day PrEP initiation, FHT use and self-collection of samples
      (SCS) for STI testing may influence prevention choices, the investigators will conduct
      in-depth interviews with participants and their sexual partners to assess perceptions and
      experiences with same-day PrEP, real-time drug level feedback, use of FHT, SCS, and how
      self-care interventions could empower trans women to engage in prevention services.

      Hypothesis: Same-day PrEP initiation will be a feasible and acceptable entryway into PrEP
      care among trans women.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomized in a 1:1 ratio to either quarterly Integrated Next Steps Counseling (iNSC) using point-of-care (POC) urine tenofovir (TFV) levels [intervention arm] or standard adherence counseling without drug level feedback [control arm].
primary purpose: Prevention
masking: None (Open Label)
measure: Feasibility of same-day initiation of F/TAF as PrEP as measured by participant engagement until the end of study
time frame: 12 months
description: Proportion retained on PrEP at months 3, 6, 9 and 12
measure: Acceptability of peer-delivered combination HIV prevention as measured by the System Usability Scale
time frame: 12 months
description: System Usability Scale scores range from 0 to 100; higher scores mean better acceptability
measure: Adoption of same-day PrEP initiation as measured by structured questionnaires
time frame: 12 months
description: Proportion initiating same-day PrEP at enrollment
measure: Fidelity to iNSC assessed through audio-recorded drug level feedback counseling sessions
time frame: 12 months
description: Proportion of research nurses successfully implementing iNSC
measure: PrEP persistence as measured by intracellular tenofovir diphosphate levels in dried blood spots at months 3, 6, 9, 12
time frame: 12 months
description: Proportion with tenofovir diphosphate levels >900 fmol per punch
measure: Sexual risk behaviors assessed through structured questionnaires
time frame: 12 months
description: Proportion reporting unprotected sex, sexual frequency
measure: STI incidence assessed through GeneXpert testing
time frame: 12 months
description: Neisseria gonorrhoeae and Chlamydia trachomatis incidence
arm group label: Integrated Next Steps Counseling using poi
arm group type: Active Comparator
description: At quarterly visits, intervention arm participants will receive iNSC Support Level 1 to address PrEP adherence and sexual health needs. Those with urine TFV levels <1000 ng/mL will receive iNSC Support Level 2, in which participant responses to two 7-item questionnaires on PrEP adherence and sexual health will guide problem solving on improved dosing.
arm group label: Standard adherence counseling
arm group type: No Intervention
description: Control arm participants will receive standard adherence counseling.
intervention type: Combination Product
intervention name: Integrated Next Steps Counseling with Real-Time Drug Level Feedback
description: Integrated next steps counseling with real-time drug level feedback using point-of-care urine tenofovir testing at quarterly visits
arm group label: Integrated Next Steps Counseling using poi
criteria: 
gender: Male
gender based: Yes
gender description: Self-identify as transgender women
minimum age: 14 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Andrew Mujugira, PhD
role: Principal Investigator
affiliation: Infectious Diseases Institute
last name: Andrew Mujugira, PhD
phone: +256 754 173 225
email: amujugira@idi.co.ug
last name: Yvonne Kamara, BA
phone: +256 777 008 598
email: ykamara@idi.co.ug
facility: 
status: Recruiting
contact: 
country: Uganda
responsible party type: Sponsor
mesh term: Sexually Transmitted Diseases
mesh term: Sexually Transmitted Diseases, Bacterial