<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/NCT03032575</url>
  </required_header>
  <id_info>
    <org_study_id>HPV in MSM with AHI</org_study_id>
    <nct_id>NCT03032575</nct_id>
  </id_info>
  <brief_title>Anal HPV Infection and Risk for Anal High-grade Squamous Intraepithelial Lesion Among Thai MSM With Acute HIV Infection</brief_title>
  <official_title>SEARCH Thailand and Thai Red Cross AIDS Research Centre</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thai Red Cross AIDS Research Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SEARCH Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>amfAR, The Foundation for AIDS Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>TREAT Asia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Thai Red Cross AIDS Research Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      1. To determine the prevalence and incidence of anal HSIL and associated risk factors among&#xD;
      MSM who initiate ART during AHI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anal human papillomavirus (HPV) infection is very common in men who have sex with men&#xD;
      (MSM).1-3 HIV-positive MSM have a higher prevalence of anal HPV infection than HIV-negative&#xD;
      MSM and are more likely to have infection with multiple HPV types.1,2 Spontaneous clearance&#xD;
      of anal HPV infection is less common among HIV- positive compared with HIV-negative MSM.2&#xD;
      Persistent anal HPV infection, particularly with high-risk HPV types, is an important risk&#xD;
      factor for the development of anal cancer.4-6 The incidence of anal cancer among HIV-positive&#xD;
      MSM is very high, ranging from 75 to 137 per 100,000 person-years, and is five times higher&#xD;
      than that in HIV-negative MSM.7-10 Anal high-grade squamous intraepithelial lesion (HSIL) is&#xD;
      the putative precursor of anal cancer.11-13 Anal squamous intraepithelial lesion has a&#xD;
      dynamic picture of temporal progression and regression, but HSIL is much less likely to&#xD;
      regress than low-grade squamous intraepithelial lesion (LSIL).10,14 A recent systematic&#xD;
      review and meta-analysis showed the pooled prevalence of anal HSIL to be 29.1% in&#xD;
      HIV-positive MSM and 21.5% in HIV-negative MSM.15 Anal HSIL incidence ranged from 8.5 to&#xD;
      15.4% per year in HIV-positive MSM and 3.3 to 6.0% per year in HIV-negative MSM. Although&#xD;
      data are limited, previous studies have shown a 9-15% progression rate from anal HSIL to anal&#xD;
      cancer during a median follow-up of 3 - 5 years. 11-13 Previous research at the Thai Red&#xD;
      Cross AIDS Research Centre has demonstrated high rates of HPV infection and anal HSIL among&#xD;
      Thai MSM, with HIV-positive MSM disproportionately affected. Prevalence of anal infection&#xD;
      with high-risk HPV types was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (p =&#xD;
      0.008).16 Prevalence of anal HSIL was 18.9% in HIV-positive MSM and 11.4% in HIV-negative MSM&#xD;
      (p = 0.1), while incidence of anal HSIL over 12 months was 29% and 8%, respectively&#xD;
      (p=0.001).17 HIV-positive MSM in that study, however, were mainly naïve to antiretroviral&#xD;
      therapy (ART) at enrollment (87% not on ART) and only 10% had undetectable HIV viral load at&#xD;
      baseline.&#xD;
&#xD;
      It is not clear if the higher rates of HPV infection and persistence of infection are due to&#xD;
      HIV infection or to different risk behavior among HIV-positive MSM. Data are inconclusive on&#xD;
      whether the use of ART has an effect on anal HPV infection among HIV-positive MSM.18-19&#xD;
      Furthermore, there is no data on the effect that &quot;early diagnosis&quot; of HIV infection and&#xD;
      &quot;early treatment&quot; with ART might have on incidence and persistence of HPV infection or on the&#xD;
      development of anal HSIL.&#xD;
&#xD;
      We propose a longitudinal, observational study of HPV infection and anal HSIL among&#xD;
      HIV-positive Thai MSM who initiate ART during acute HIV infection (AHI). The hypothesis is&#xD;
      that early HIV diagnosis and early ART within the first 4 weeks of infection will mitigate&#xD;
      immunological and virological factors that increase HPV persistence and anal HSIL incidence&#xD;
      in HIV-positive MSM such that these measure will be significantly lower when compared to&#xD;
      historical controls of chronically-infected HIV-positive Thai MSM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Actual">December 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The prevalence and incidence of anal HSIL among MSM who initiate ART during AHI will be lower than among chronically-infected HIV-positive MSM, Anal HSIL is diagnosed based on histology specimen and cytology (2001 Bethesda system)</measure>
    <time_frame>12 months</time_frame>
    <description>The prevalence of anal HSIL and the incidence of anal HSIL during the follow-up period. Anal HSIL is diagnosed based on histology specimen. A composite anal HSIL outcome (including both cytologic HSIL/ASC-H and histologic HSIL) will also be used.&#xD;
Incidence of HSIL during the follow-up period will be calculated as the number of new diagnoses per person time at risk. 95% confidence intervals (CI) will be calculated assuming a Poisson distribution. Cox proportional hazards regression will be used to identify factors associated with incident HSIL.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Human Papillomavirus Infection</condition>
  <arm_group>
    <arm_group_label>sample size 100</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Study Design: This is a prospective observational cohort of Thai MSM who initiated ART at the time of AHI, defined as the first 30 days after HIV acquisition (Fiebig stages 1 through 5). Volunteers will be examined at baseline to determine the prevalence of HPV infection and HSIL at HIV diagnosis. They will then be followed longitudinally for new incidence of HPV and HSIL, as well as progression or regression of existing lesions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>SEARCH010/RV254</intervention_name>
    <arm_group_label>sample size 100</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 years or above.&#xD;
&#xD;
          2. Born biological male.&#xD;
&#xD;
          3. Self-identifies as MSM or transgender woman.&#xD;
&#xD;
          4. Enrolled in the SEARCH010/RV254 cohort.&#xD;
&#xD;
          5. In the stage of acute HIV infection diagnosed within 7 days (Fiebig I-V).&#xD;
&#xD;
          6. Agrees to start ART during acute HIV infection.&#xD;
&#xD;
          7. Had sex with a male partner at least once in the previous 3 months&#xD;
&#xD;
          8. Consents to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Any history of previous HSIL diagnosis or treatment.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nittaya Phanuphak, M.D.,Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Thai Red Cross AIDS Research Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Thai Red Cross AIDS Research Centre</name>
      <address>
        <city>Pathum Wan</city>
        <state>Bangkok</state>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>April 11, 2023</last_update_submitted>
  <last_update_submitted_qc>April 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Papillomavirus Infections</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/NCT03032575
org study id: HPV in MSM with AHI
nct id: NCT03032575
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
1. To determine the prevalence and incidence of anal HSIL and associated risk factors among
      MSM who initiate ART during AHI.
Anal human papillomavirus (HPV) infection is very common in men who have sex with men
      (MSM).1-3 HIV-positive MSM have a higher prevalence of anal HPV infection than HIV-negative
      MSM and are more likely to have infection with multiple HPV types.1,2 Spontaneous clearance
      of anal HPV infection is less common among HIV- positive compared with HIV-negative MSM.2
      Persistent anal HPV infection, particularly with high-risk HPV types, is an important risk
      factor for the development of anal cancer.4-6 The incidence of anal cancer among HIV-positive
      MSM is very high, ranging from 75 to 137 per 100,000 person-years, and is five times higher
      than that in HIV-negative MSM.7-10 Anal high-grade squamous intraepithelial lesion (HSIL) is
      the putative precursor of anal cancer.11-13 Anal squamous intraepithelial lesion has a
      dynamic picture of temporal progression and regression, but HSIL is much less likely to
      regress than low-grade squamous intraepithelial lesion (LSIL).10,14 A recent systematic
      review and meta-analysis showed the pooled prevalence of anal HSIL to be 29.1% in
      HIV-positive MSM and 21.5% in HIV-negative MSM.15 Anal HSIL incidence ranged from 8.5 to
      15.4% per year in HIV-positive MSM and 3.3 to 6.0% per year in HIV-negative MSM. Although
      data are limited, previous studies have shown a 9-15% progression rate from anal HSIL to anal
      cancer during a median follow-up of 3 - 5 years. 11-13 Previous research at the Thai Red
      Cross AIDS Research Centre has demonstrated high rates of HPV infection and anal HSIL among
      Thai MSM, with HIV-positive MSM disproportionately affected. Prevalence of anal infection
      with high-risk HPV types was 57.5% in HIV-positive and 36.6% in HIV-negative MSM (p =
      0.008).16 Prevalence of anal HSIL was 18.9% in HIV-positive MSM and 11.4% in HIV-negative MSM
      (p = 0.1), while incidence of anal HSIL over 12 months was 29% and 8%, respectively
      (p=0.001).17 HIV-positive MSM in that study, however, were mainly naïve to antiretroviral
      therapy (ART) at enrollment (87% not on ART) and only 10% had undetectable HIV viral load at
      baseline.

      It is not clear if the higher rates of HPV infection and persistence of infection are due to
      HIV infection or to different risk behavior among HIV-positive MSM. Data are inconclusive on
      whether the use of ART has an effect on anal HPV infection among HIV-positive MSM.18-19
      Furthermore, there is no data on the effect that "early diagnosis" of HIV infection and
      "early treatment" with ART might have on incidence and persistence of HPV infection or on the
      development of anal HSIL.

      We propose a longitudinal, observational study of HPV infection and anal HSIL among
      HIV-positive Thai MSM who initiate ART during acute HIV infection (AHI). The hypothesis is
      that early HIV diagnosis and early ART within the first 4 weeks of infection will mitigate
      immunological and virological factors that increase HPV persistence and anal HSIL incidence
      in HIV-positive MSM such that these measure will be significantly lower when compared to
      historical controls of chronically-infected HIV-positive Thai MSM.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The prevalence and incidence of anal HSIL among MSM who initiate ART during AHI will be lower than among chronically-infected HIV-positive MSM, Anal HSIL is diagnosed based on histology specimen and cytology (2001 Bethesda system)
time frame: 12 months
description: The prevalence of anal HSIL and the incidence of anal HSIL during the follow-up period. Anal HSIL is diagnosed based on histology specimen. A composite anal HSIL outcome (including both cytologic HSIL/ASC-H and histologic HSIL) will also be used.
Incidence of HSIL during the follow-up period will be calculated as the number of new diagnoses per person time at risk. 95% confidence intervals (CI) will be calculated assuming a Poisson distribution. Cox proportional hazards regression will be used to identify factors associated with incident HSIL.
arm group label: sample size 100
arm group type: Other
description: Study Design: This is a prospective observational cohort of Thai MSM who initiated ART at the time of AHI, defined as the first 30 days after HIV acquisition (Fiebig stages 1 through 5). Volunteers will be examined at baseline to determine the prevalence of HPV infection and HSIL at HIV diagnosis. They will then be followed longitudinally for new incidence of HPV and HSIL, as well as progression or regression of existing lesions.
intervention type: Behavioral
intervention name: SEARCH010/RV254
arm group label: sample size 100
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Nittaya Phanuphak, M.D.,Ph.D.
role: Principal Investigator
affiliation: The Thai Red Cross AIDS Research Centre
facility: 
country: Thailand
responsible party type: Sponsor
mesh term: Infections
mesh term: Papillomavirus Infections