<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/NCT01691768</url>
  </required_header>
  <id_info>
    <org_study_id>CAPRISA008</org_study_id>
    <nct_id>NCT01691768</nct_id>
    <nct_alias>NCT01645813</nct_alias>
  </id_info>
  <brief_title>Implementation Effectiveness and Safety of Tenofovir Gel Provision Through Family Planning Services</brief_title>
  <official_title>Open-Label Randomized Controlled Trial to Assess the Implementation Effectiveness and Safety of 1% Tenofovir Gel Provision Through Family Planning Services in KwaZulu-Natal, South Africa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for the AIDS Programme of Research in South Africa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CONRAD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>FHI 360</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute for Healthcare Improvement</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for the AIDS Programme of Research in South Africa</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effectiveness of an implementation model which&#xD;
      integrates tenofovir gel provision into existing family planning services.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The CAPRISA 008 trial is a two-arm, open-label, randomized controlled trial that is being&#xD;
      conducted at the CAPRISA eThekwini and CAPRISA Vulindlela Clinics and their neighboring&#xD;
      public sector family planning services in KwaZulu-Natal, South Africa. Up to 700 consenting&#xD;
      sexually active, HIV-uninfected women aged 18 years and older who previously participated in&#xD;
      an antiretroviral (ARV) prevention study will be enrolled and followed for a maximum 30&#xD;
      months. All women will be provided with 1% tenofovir gel but will be randomised to either&#xD;
      receive their gel through a public sector family planning services with 2-3 monthly provision&#xD;
      (intervention arm) or through the CAPRISA research clinics with monthly provision (control&#xD;
      arm).&#xD;
&#xD;
      All women in the trial will be provided with the standard package of HIV prevention and&#xD;
      reproductive health services. Participants in both study arms will be provided with a supply&#xD;
      of single-use, pre-filled applicators of 1% tenofovir gel. While in the study, participants&#xD;
      will be advised and supported to follow the CAPRISA 004 pre- and post-dosing strategy, namely&#xD;
      BAT24, where the first dose of tenofovir gel is applied within 12 hours before anticipated&#xD;
      coitus and a second dose as soon as possible but within 12 hours after coitus, with a maximum&#xD;
      of two doses of gel in a 24-hour period.&#xD;
&#xD;
      The primary objective of this trial is to assess the effectiveness of an implementation model&#xD;
      for tenofovir gel provision through family planning services.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 2/Phase 3</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Number of Returned Used Applicators Per Month (i.e in 30 Days)</measure>
    <time_frame>Between 2012 to 2015, up to 28 months</time_frame>
    <description>The primary endpoint is the mean number of returned used applicators per month. Since participants in the intervention arm followed two and three monthly schedule (as opposed to monthly in the intervention arm), the number of returned used applicators per month for each participant will be estimated as the total number of returned applicators at that visit divided by the number of days since the previous visit, multiplied by 30. Thus a uniform distribution of gel use will be assumed in participants whom we did not see monthly. Intent to treat and per protocol analyses were carried out of this outcome. Intent to treat population includes all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data. The per protocol population is a subset of the intent to treat population.The per-protocol analysis excluded visits where no gel had been dispensed for &gt;120 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HIV Incidence Rates</measure>
    <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
    <description>Time to HIV infection was calculated as the difference between estimated date of infection (midpoint between the last negative HIV test date and the first confirmed positive HIV test date) and enrolment date, plus one. Where a participant has a positive PCR and a negative rapid test on the same date, the date of infection is calculated as 14 days prior to this date. Women who do not become HIV positive before their last study visit will be censored on the day of their last negative HIV test. Their follow-up time will be calculated as the difference between date of censoring and enrolment date, plus one.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy Incidence Rates</measure>
    <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
    <description>Time to pregnancy, was as the difference between the estimated date of conception and the enrolment date, plus one. The date of conception was defined as 14 days after the last normal menstrual period or the estimated date of delivery minus 40 weeks if the first date of last normal menstrual period is not available or the midpoint between the date of the first positive pregnancy test and the date of the previous negative pregnancy test. The censoring time for a woman who did not become pregnant during the study equals the difference between the calculated censoring date and the enrolment date, plus one.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Adherence &gt;80%.</measure>
    <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
    <description>Self-reported adherence to the tenofovir gel dosing strategy.Gel adherence was defined as the estimated proportion of reported sex acts covered by two gel doses and calculated for each woman by dividing half the number of returned used applicators each month by the number of reported sex acts that month.For participants attending 2-3 monthly clinic visits, their number of gels used in the last 30 days will be estimated as the total number of returned used gels, divided by the number of days between the current and the previous visit, times 30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV Viral Load Among HIV Seroconverters</measure>
    <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
    <description>This is mean log transformed HIV viral load measured at the first visit post HIV infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tenofovir Resistance Among HIV Seroconverters</measure>
    <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Human Papillomavirus Incidence Rates</measure>
    <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
    <description>For the calculation of the incidence rate, seroconversion was assumed to have occurred at the midpoint between the first positive HPV test and the previous HPV negative test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up</measure>
    <time_frame>All participants with drug levels at 12 months of follow-up</time_frame>
    <description>Percentage of participants with detectable tenofovir levels from vaginal samples at 12 months of follow-up. All drug levels below limit of quantification were considered to be undetectable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Product Acceptability</measure>
    <time_frame>At study completion, up to 28 months</time_frame>
    <description>This is the number of participants who reported that they liked the study product. The questionnaire was administered at study exit, therefore participants who were loss to follow-up and those who died could not complete the questionnaire.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">372</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1% tenofovir gel</intervention_name>
    <description>Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years and older&#xD;
&#xD;
          -  Women who previously participated in an ARV prevention study&#xD;
&#xD;
          -  Currently utilizing or agreeing to attend designated public sector family planning&#xD;
             services&#xD;
&#xD;
          -  Able and willing to provide first person informed consent to be screened for, and to&#xD;
             enroll in, the study&#xD;
&#xD;
          -  Able and willing to provide adequate locator information for study retention purposes&#xD;
&#xD;
          -  Sexually active (at least one coital act in the last 3 months prior to screening)&#xD;
&#xD;
          -  HIV negative (by HIV testing performed by study staff within 30 days of enrollment)&#xD;
&#xD;
          -  Negative pregnancy test performed by study staff within 21 days of enrollment&#xD;
&#xD;
          -  Agree to use a non-barrier form of contraceptive&#xD;
&#xD;
          -  Agree to adhere to study visits and procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a creatinine clearance &lt; 50ml/min&#xD;
&#xD;
          -  Has any other condition that, based on the opinion of the Investigator or designee,&#xD;
             would preclude provision of informed consent, make participation in the study unsafe,&#xD;
             complicate interpretation of study outcome data, or otherwise interfere with achieving&#xD;
             the study objectives&#xD;
      </textblock>
    </criteria>
    <gender>Female</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>Quarraisha Abdool Karim, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for the AIDS Programme of Research in South Africa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CAPRISA eThekwini Clinical Research Site</name>
      <address>
        <city>Durban</city>
        <state>KwaZulu-Natal</state>
        <zip>4001</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CAPRISA Vulindlela Clinical Research Site</name>
      <address>
        <city>Pietermaritzburg</city>
        <state>KwaZulu-Natal</state>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <link>
    <url>http://www.caprisa.org</url>
    <description>Centre for the AIDS Programme of Research in South Africa web site</description>
  </link>
  <reference>
    <citation>Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19. Erratum In: Science. 2011 Jul 29;333(6042):524.</citation>
    <PMID>20643915</PMID>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>July 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>October 10, 2019</results_first_submitted>
  <results_first_submitted_qc>November 7, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 26, 2019</results_first_posted>
  <last_update_submitted>November 7, 2019</last_update_submitted>
  <last_update_submitted_qc>November 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for the AIDS Programme of Research in South Africa</investigator_affiliation>
    <investigator_full_name>Dr Quarraisha Abdool Karim</investigator_full_name>
    <investigator_title>Associate Scientific Director</investigator_title>
  </responsible_party>
  <keyword>microbicides</keyword>
  <keyword>women</keyword>
  <keyword>HIV prevention</keyword>
  <keyword>PrEP</keyword>
  <keyword>Tenofovir gel</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>448 were assessed for eligibility and 382 were randomized. However, only 372 were eligible for study participation. Of the 10 who were ineligibly enrolled: 6 were HIV positive at enrollment, 2 were co-enrolled in another trial, 1 had no post-randomization follow-up data and 1 was pregnant at enrollment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intervention</title>
          <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="189"/>
                <participants group_id="P2" count="183"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="174"/>
                <participants group_id="P2" count="167"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Relocated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent to treat population was analyzed. All participants who were randomized and met the pre-enrollment eligibility criteria.</population>
      <group_list>
        <group group_id="B1">
          <title>Intervention</title>
          <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="189"/>
            <count group_id="B2" value="183"/>
            <count group_id="B3" value="372"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="189"/>
                    <count group_id="B2" value="183"/>
                    <count group_id="B3" value="372"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.5" spread="5.8"/>
                    <measurement group_id="B2" value="29.3" spread="5.3"/>
                    <measurement group_id="B3" value="29.4" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="189"/>
                    <count group_id="B2" value="183"/>
                    <count group_id="B3" value="372"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="372"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="189"/>
                    <count group_id="B2" value="183"/>
                    <count group_id="B3" value="372"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="372"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>South Africa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="189"/>
                    <count group_id="B2" value="183"/>
                    <count group_id="B3" value="372"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="372"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex acts in past 30 days</title>
          <units>Acts</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="189"/>
                    <count group_id="B2" value="183"/>
                    <count group_id="B3" value="372"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4" lower_limit="3" upper_limit="8"/>
                    <measurement group_id="B2" value="4" lower_limit="2" upper_limit="8"/>
                    <measurement group_id="B3" value="4" lower_limit="2" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Contraception</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="189"/>
                    <count group_id="B2" value="183"/>
                    <count group_id="B3" value="372"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Injectable</title>
                  <measurement_list>
                    <measurement group_id="B1" value="139"/>
                    <measurement group_id="B2" value="140"/>
                    <measurement group_id="B3" value="279"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Oral</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Sterilized</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HSV-2 prevalence</title>
          <population>A total of 9 participants had equivocal results and 2 had missing results.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="182"/>
                    <count group_id="B2" value="179"/>
                    <count group_id="B3" value="361"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="174"/>
                    <measurement group_id="B2" value="159"/>
                    <measurement group_id="B3" value="333"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HPV prevalence</title>
          <population>Total of 5 participants had equivocal and 2 had missing results.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="186"/>
                    <count group_id="B2" value="179"/>
                    <count group_id="B3" value="365"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Number of Returned Used Applicators Per Month (i.e in 30 Days)</title>
        <description>The primary endpoint is the mean number of returned used applicators per month. Since participants in the intervention arm followed two and three monthly schedule (as opposed to monthly in the intervention arm), the number of returned used applicators per month for each participant will be estimated as the total number of returned applicators at that visit divided by the number of days since the previous visit, multiplied by 30. Thus a uniform distribution of gel use will be assumed in participants whom we did not see monthly. Intent to treat and per protocol analyses were carried out of this outcome. Intent to treat population includes all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data. The per protocol population is a subset of the intent to treat population.The per-protocol analysis excluded visits where no gel had been dispensed for &gt;120 days.</description>
        <time_frame>Between 2012 to 2015, up to 28 months</time_frame>
        <population>Intent to treat population and the per protocol population (excluding all subsequent data collected from participants who were not dispensed product for more than 120 days).</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Number of Returned Used Applicators Per Month (i.e in 30 Days)</title>
          <description>The primary endpoint is the mean number of returned used applicators per month. Since participants in the intervention arm followed two and three monthly schedule (as opposed to monthly in the intervention arm), the number of returned used applicators per month for each participant will be estimated as the total number of returned applicators at that visit divided by the number of days since the previous visit, multiplied by 30. Thus a uniform distribution of gel use will be assumed in participants whom we did not see monthly. Intent to treat and per protocol analyses were carried out of this outcome. Intent to treat population includes all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data. The per protocol population is a subset of the intent to treat population.The per-protocol analysis excluded visits where no gel had been dispensed for &gt;120 days.</description>
          <population>Intent to treat population and the per protocol population (excluding all subsequent data collected from participants who were not dispensed product for more than 120 days).</population>
          <units>Used gel applicators per month</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="189"/>
                <count group_id="O2" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Intent to treat analyses</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="189"/>
                    <count group_id="O2" value="183"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" lower_limit="4.7" upper_limit="5.7"/>
                    <measurement group_id="O2" value="5.7" lower_limit="5.2" upper_limit="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Per protocol analyses</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="176"/>
                    <count group_id="O2" value="175"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" lower_limit="5.0" upper_limit="6.1"/>
                    <measurement group_id="O2" value="5.8" lower_limit="5.3" upper_limit="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Intent to treat population (all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data) was used for this analyses.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>We estimated that we would need to enrol 700 women after taking into account the anticipated loss-to follow-up in order to provide 90% power to demonstrate whether gel use in women attending family planning (intervention) services is similar to, but no more than 20% lower than, gel use among women attending CAPRISA research clinics (control).</non_inferiority_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.16</ci_lower_limit>
            <ci_upper_limit>0.21</ci_upper_limit>
            <estimate_desc>The least square mean from the intervention arm was the minuend and the least square mean from the control arm was the subtrahend.</estimate_desc>
            <other_analysis_desc>The primary endpoint was compared using univariate linear mixed model with compound symmetry structure.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This is the analyses from the per protocol population (excluding all subsequent data collected from participants who were not dispensed product for more than 120 days).</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>We estimated that we would need to enrol 700 women after taking into account the anticipated loss-to follow-up in order to provide 90% power to demonstrate whether gel use in women attending family planning (intervention) services is similar to, but no more than 20% lower than, gel use among women attending CAPRISA research clinics (control)</non_inferiority_desc>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-0.25</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.98</ci_lower_limit>
            <ci_upper_limit>0.48</ci_upper_limit>
            <estimate_desc>We calculated the difference in means between the two arms. The mean from the intervention arm was the minuend and the mean from the control arm was the subtrahend.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>HIV Incidence Rates</title>
        <description>Time to HIV infection was calculated as the difference between estimated date of infection (midpoint between the last negative HIV test date and the first confirmed positive HIV test date) and enrolment date, plus one. Where a participant has a positive PCR and a negative rapid test on the same date, the date of infection is calculated as 14 days prior to this date. Women who do not become HIV positive before their last study visit will be censored on the day of their last negative HIV test. Their follow-up time will be calculated as the difference between date of censoring and enrolment date, plus one.</description>
        <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
        <population>Intent to treat population(all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data).</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of Quality Improvement methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>HIV Incidence Rates</title>
          <description>Time to HIV infection was calculated as the difference between estimated date of infection (midpoint between the last negative HIV test date and the first confirmed positive HIV test date) and enrolment date, plus one. Where a participant has a positive PCR and a negative rapid test on the same date, the date of infection is calculated as 14 days prior to this date. Women who do not become HIV positive before their last study visit will be censored on the day of their last negative HIV test. Their follow-up time will be calculated as the difference between date of censoring and enrolment date, plus one.</description>
          <population>Intent to treat population(all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data).</population>
          <units>Incidence rate/100 women years</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="189"/>
                <count group_id="O2" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="1.8" upper_limit="6.0"/>
                    <measurement group_id="O2" value="3.6" lower_limit="1.9" upper_limit="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The power was not calculated for all the secondary outcomes.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.928</p_value>
            <method>z-test</method>
            <method_desc>We used z-test to compare incidence rates between the arms. We did not use log-rank test because we did not present survival curves.</method_desc>
            <param_type>Incidence rate ratio</param_type>
            <param_value>0.96</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.40</ci_lower_limit>
            <ci_upper_limit>2.35</ci_upper_limit>
            <estimate_desc>We calculated incidence rate ratio, where the HIV incidence rate for the intervention arm represents the numerator and the HIV incidence rate for the control arm represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pregnancy Incidence Rates</title>
        <description>Time to pregnancy, was as the difference between the estimated date of conception and the enrolment date, plus one. The date of conception was defined as 14 days after the last normal menstrual period or the estimated date of delivery minus 40 weeks if the first date of last normal menstrual period is not available or the midpoint between the date of the first positive pregnancy test and the date of the previous negative pregnancy test. The censoring time for a woman who did not become pregnant during the study equals the difference between the calculated censoring date and the enrolment date, plus one.</description>
        <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
        <population>Intent to treat population(all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data).</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of Quality Improvement methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Pregnancy Incidence Rates</title>
          <description>Time to pregnancy, was as the difference between the estimated date of conception and the enrolment date, plus one. The date of conception was defined as 14 days after the last normal menstrual period or the estimated date of delivery minus 40 weeks if the first date of last normal menstrual period is not available or the midpoint between the date of the first positive pregnancy test and the date of the previous negative pregnancy test. The censoring time for a woman who did not become pregnant during the study equals the difference between the calculated censoring date and the enrolment date, plus one.</description>
          <population>Intent to treat population(all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data).</population>
          <units>Incidence rate/100 women years</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="189"/>
                <count group_id="O2" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" lower_limit="2.8" upper_limit="7.9"/>
                    <measurement group_id="O2" value="5.1" lower_limit="2.9" upper_limit="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Power was not calculated for all the secondary outcomes.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.895</p_value>
            <method>z-test</method>
            <method_desc>We used z-test to compare pregnancy incidence rates between the arms. We did not use log-rank test because we did not present survival curves.</method_desc>
            <param_type>incidence rate ratio</param_type>
            <param_value>0.96</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.45</ci_lower_limit>
            <ci_upper_limit>2.04</ci_upper_limit>
            <estimate_desc>We calculated incidence rate ratio, where the pregnancy incidence rate for the intervention arm represents the numerator and the pregnancy incidence rate for the control arm represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Adherence &gt;80%.</title>
        <description>Self-reported adherence to the tenofovir gel dosing strategy.Gel adherence was defined as the estimated proportion of reported sex acts covered by two gel doses and calculated for each woman by dividing half the number of returned used applicators each month by the number of reported sex acts that month.For participants attending 2-3 monthly clinic visits, their number of gels used in the last 30 days will be estimated as the total number of returned used gels, divided by the number of days between the current and the previous visit, times 30.</description>
        <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
        <population>This is a subset of intent to treat population. It includes all participants who returned used gel applicators and also reported sex during follow-up.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of Quality Improvement methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Adherence &gt;80%.</title>
          <description>Self-reported adherence to the tenofovir gel dosing strategy.Gel adherence was defined as the estimated proportion of reported sex acts covered by two gel doses and calculated for each woman by dividing half the number of returned used applicators each month by the number of reported sex acts that month.For participants attending 2-3 monthly clinic visits, their number of gels used in the last 30 days will be estimated as the total number of returned used gels, divided by the number of days between the current and the previous visit, times 30.</description>
          <population>This is a subset of intent to treat population. It includes all participants who returned used gel applicators and also reported sex during follow-up.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="188"/>
                <count group_id="O2" value="181"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.2" lower_limit="63.1" upper_limit="76.7"/>
                    <measurement group_id="O2" value="65.2" lower_limit="57.8" upper_limit="72.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Power was not calculated for all secondary outcomes.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.304</p_value>
            <method>Regression, Log-binomial</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.94</ci_lower_limit>
            <ci_upper_limit>1.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>HIV Viral Load Among HIV Seroconverters</title>
        <description>This is mean log transformed HIV viral load measured at the first visit post HIV infection.</description>
        <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
        <population>All participants who became HIV infected</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of Quality Improvement methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>HIV Viral Load Among HIV Seroconverters</title>
          <description>This is mean log transformed HIV viral load measured at the first visit post HIV infection.</description>
          <population>All participants who became HIV infected</population>
          <units>log10 copies/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4" spread="1.3"/>
                    <measurement group_id="O2" value="4.8" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.455</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tenofovir Resistance Among HIV Seroconverters</title>
        <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
        <population>Due to lack of funding, tenofovir resistance testing was not done in this study. However, we do have stored samples to fall back onto, should we secure funding.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of Quality Improvement methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Tenofovir Resistance Among HIV Seroconverters</title>
          <population>Due to lack of funding, tenofovir resistance testing was not done in this study. However, we do have stored samples to fall back onto, should we secure funding.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Human Papillomavirus Incidence Rates</title>
        <description>For the calculation of the incidence rate, seroconversion was assumed to have occurred at the midpoint between the first positive HPV test and the previous HPV negative test.</description>
        <time_frame>Between 2012 and 2015, up to 28 months</time_frame>
        <population>This is the subset of intent to treat population. It includes all participants who had HPV negative results at randomisation.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Human Papillomavirus Incidence Rates</title>
          <description>For the calculation of the incidence rate, seroconversion was assumed to have occurred at the midpoint between the first positive HPV test and the previous HPV negative test.</description>
          <population>This is the subset of intent to treat population. It includes all participants who had HPV negative results at randomisation.</population>
          <units>Incidence rate/100 women years</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="166"/>
                <count group_id="O2" value="168"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.2" upper_limit="2.9"/>
                    <measurement group_id="O2" value="3.0" lower_limit="1.4" upper_limit="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.097</p_value>
            <method>z-test</method>
            <param_type>incidence rate ratio</param_type>
            <param_value>0.33</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.06</ci_lower_limit>
            <ci_upper_limit>1.32</ci_upper_limit>
            <estimate_desc>We calculated incidence rate ratio, where the HPV incidence rate for the intervention arm represents the numerator and the HPV incidence rate for the control arm represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up</title>
        <description>Percentage of participants with detectable tenofovir levels from vaginal samples at 12 months of follow-up. All drug levels below limit of quantification were considered to be undetectable.</description>
        <time_frame>All participants with drug levels at 12 months of follow-up</time_frame>
        <population>All participants with drug levels measured at 12 months of follow-up</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up</title>
          <description>Percentage of participants with detectable tenofovir levels from vaginal samples at 12 months of follow-up. All drug levels below limit of quantification were considered to be undetectable.</description>
          <population>All participants with drug levels measured at 12 months of follow-up</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="157"/>
                <count group_id="O2" value="156"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.5" lower_limit="32.2" upper_limit="47.3"/>
                    <measurement group_id="O2" value="43.6" lower_limit="36.1" upper_limit="51.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.462</p_value>
            <method>Regression, Log-binomial</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.70</ci_lower_limit>
            <ci_upper_limit>1.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Product Acceptability</title>
        <description>This is the number of participants who reported that they liked the study product. The questionnaire was administered at study exit, therefore participants who were loss to follow-up and those who died could not complete the questionnaire.</description>
        <time_frame>At study completion, up to 28 months</time_frame>
        <population>Participants who completed product acceptability questionnaire at study exit</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of Quality Improvement methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
          </group>
        </group_list>
        <measure>
          <title>Product Acceptability</title>
          <description>This is the number of participants who reported that they liked the study product. The questionnaire was administered at study exit, therefore participants who were loss to follow-up and those who died could not complete the questionnaire.</description>
          <population>Participants who completed product acceptability questionnaire at study exit</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="184"/>
                <count group_id="O2" value="177"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="180"/>
                    <measurement group_id="O2" value="170"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Between 2012 and 2015, up to 28 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intervention</title>
          <description>1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of QI methodology to promote reliable service delivery&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics&#xD;
1% tenofovir gel: Participants will be randomized to receive 1% tenofovir gel through either:&#xD;
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or&#xD;
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="189"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Anal sphincter atony</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Crohn's disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Oesophageal candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Post procedural sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Hand fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Soft tissue mass</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Ameloblastoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Complication of pregnancy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Gestational hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Pre-eclampsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Premature labour</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Ruptured ectopic pregnancy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Schizoaffective disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Calculus ureteric</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="189"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Neurogenic bladder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Anoplasty</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="189"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Caesarean section</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="189"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 15.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="166" subjects_at_risk="189"/>
                <counts group_id="E2" subjects_affected="181" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis allergic</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="189"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="189"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" events="15" subjects_affected="14" subjects_at_risk="189"/>
                <counts group_id="E2" events="19" subjects_affected="17" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="22" subjects_affected="21" subjects_at_risk="189"/>
                <counts group_id="E2" events="60" subjects_affected="45" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Body tinea</sub_title>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="189"/>
                <counts group_id="E2" events="18" subjects_affected="17" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="189"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="20" subjects_affected="15" subjects_at_risk="189"/>
                <counts group_id="E2" events="22" subjects_affected="18" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="27" subjects_affected="23" subjects_at_risk="189"/>
                <counts group_id="E2" events="112" subjects_affected="66" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Pelvic inflammatory disease</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="189"/>
                <counts group_id="E2" events="19" subjects_affected="16" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="22" subjects_affected="20" subjects_at_risk="189"/>
                <counts group_id="E2" events="31" subjects_affected="25" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="36" subjects_affected="27" subjects_at_risk="189"/>
                <counts group_id="E2" events="34" subjects_affected="24" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="189"/>
                <counts group_id="E2" events="20" subjects_affected="17" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Vaginitis bacterial</sub_title>
                <counts group_id="E1" events="12" subjects_affected="11" subjects_at_risk="189"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Vulvovaginitis</sub_title>
                <counts group_id="E1" events="29" subjects_affected="25" subjects_at_risk="189"/>
                <counts group_id="E2" events="49" subjects_affected="39" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pressure diastolic increased</sub_title>
                <counts group_id="E1" events="50" subjects_affected="42" subjects_at_risk="189"/>
                <counts group_id="E2" events="31" subjects_affected="27" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="26" subjects_affected="22" subjects_at_risk="189"/>
                <counts group_id="E2" events="13" subjects_affected="11" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Blood pressure systolic increased</sub_title>
                <counts group_id="E1" events="53" subjects_affected="42" subjects_at_risk="189"/>
                <counts group_id="E2" events="27" subjects_affected="20" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal loss of weight</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="189"/>
                <counts group_id="E2" events="13" subjects_affected="10" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="189"/>
                <counts group_id="E2" events="25" subjects_affected="21" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="189"/>
                <counts group_id="E2" events="19" subjects_affected="19" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="30" subjects_affected="28" subjects_at_risk="189"/>
                <counts group_id="E2" events="91" subjects_affected="62" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital ulceration</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="189"/>
                <counts group_id="E2" events="16" subjects_affected="15" subjects_at_risk="183"/>
              </event>
              <event>
                <sub_title>Vaginal discharge</sub_title>
                <counts group_id="E1" events="91" subjects_affected="67" subjects_at_risk="189"/>
                <counts group_id="E2" events="102" subjects_affected="73" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="12" subjects_affected="11" subjects_at_risk="189"/>
                <counts group_id="E2" events="33" subjects_affected="26" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="18" subjects_affected="18" subjects_at_risk="189"/>
                <counts group_id="E2" events="14" subjects_affected="11" subjects_at_risk="183"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The 2-3 monthly intervals between clinic appointments in the control arm is likely to introduce recall bias in this arm, unlike the monthly intervals in the intervention arm.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Nonhlanhla Yende-Zuma</name_or_title>
      <organization>CAPRISA</organization>
      <phone>+27 31 260 4392</phone>
      <email>nonhlanhla.yende@caprisa.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01691768
org study id: CAPRISA008
nct id: NCT01691768
nct alias: NCT01645813
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to assess the effectiveness of an implementation model which
      integrates tenofovir gel provision into existing family planning services.
The CAPRISA 008 trial is a two-arm, open-label, randomized controlled trial that is being
      conducted at the CAPRISA eThekwini and CAPRISA Vulindlela Clinics and their neighboring
      public sector family planning services in KwaZulu-Natal, South Africa. Up to 700 consenting
      sexually active, HIV-uninfected women aged 18 years and older who previously participated in
      an antiretroviral (ARV) prevention study will be enrolled and followed for a maximum 30
      months. All women will be provided with 1% tenofovir gel but will be randomised to either
      receive their gel through a public sector family planning services with 2-3 monthly provision
      (intervention arm) or through the CAPRISA research clinics with monthly provision (control
      arm).

      All women in the trial will be provided with the standard package of HIV prevention and
      reproductive health services. Participants in both study arms will be provided with a supply
      of single-use, pre-filled applicators of 1% tenofovir gel. While in the study, participants
      will be advised and supported to follow the CAPRISA 004 pre- and post-dosing strategy, namely
      BAT24, where the first dose of tenofovir gel is applied within 12 hours before anticipated
      coitus and a second dose as soon as possible but within 12 hours after coitus, with a maximum
      of two doses of gel in a 24-hour period.

      The primary objective of this trial is to assess the effectiveness of an implementation model
      for tenofovir gel provision through family planning services.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Mean Number of Returned Used Applicators Per Month (i.e in 30 Days)
time frame: Between 2012 to 2015, up to 28 months
description: The primary endpoint is the mean number of returned used applicators per month. Since participants in the intervention arm followed two and three monthly schedule (as opposed to monthly in the intervention arm), the number of returned used applicators per month for each participant will be estimated as the total number of returned applicators at that visit divided by the number of days since the previous visit, multiplied by 30. Thus a uniform distribution of gel use will be assumed in participants whom we did not see monthly. Intent to treat and per protocol analyses were carried out of this outcome. Intent to treat population includes all participants who were randomized, met pre-randomization eligibility criteria and who have post-enrollment follow-up data. The per protocol population is a subset of the intent to treat population.The per-protocol analysis excluded visits where no gel had been dispensed for >120 days.
measure: HIV Incidence Rates
time frame: Between 2012 and 2015, up to 28 months
description: Time to HIV infection was calculated as the difference between estimated date of infection (midpoint between the last negative HIV test date and the first confirmed positive HIV test date) and enrolment date, plus one. Where a participant has a positive PCR and a negative rapid test on the same date, the date of infection is calculated as 14 days prior to this date. Women who do not become HIV positive before their last study visit will be censored on the day of their last negative HIV test. Their follow-up time will be calculated as the difference between date of censoring and enrolment date, plus one.
measure: Pregnancy Incidence Rates
time frame: Between 2012 and 2015, up to 28 months
description: Time to pregnancy, was as the difference between the estimated date of conception and the enrolment date, plus one. The date of conception was defined as 14 days after the last normal menstrual period or the estimated date of delivery minus 40 weeks if the first date of last normal menstrual period is not available or the midpoint between the date of the first positive pregnancy test and the date of the previous negative pregnancy test. The censoring time for a woman who did not become pregnant during the study equals the difference between the calculated censoring date and the enrolment date, plus one.
measure: Percentage of Participants Achieving Adherence >80%.
time frame: Between 2012 and 2015, up to 28 months
description: Self-reported adherence to the tenofovir gel dosing strategy.Gel adherence was defined as the estimated proportion of reported sex acts covered by two gel doses and calculated for each woman by dividing half the number of returned used applicators each month by the number of reported sex acts that month.For participants attending 2-3 monthly clinic visits, their number of gels used in the last 30 days will be estimated as the total number of returned used gels, divided by the number of days between the current and the previous visit, times 30.
measure: HIV Viral Load Among HIV Seroconverters
time frame: Between 2012 and 2015, up to 28 months
description: This is mean log transformed HIV viral load measured at the first visit post HIV infection.
measure: Tenofovir Resistance Among HIV Seroconverters
time frame: Between 2012 and 2015, up to 28 months
measure: Human Papillomavirus Incidence Rates
time frame: Between 2012 and 2015, up to 28 months
description: For the calculation of the incidence rate, seroconversion was assumed to have occurred at the midpoint between the first positive HPV test and the previous HPV negative test.
measure: Percentage of Participants With Detectable Tenofovir Levels From Vaginal Samples at 12 Months of Follow-up
time frame: All participants with drug levels at 12 months of follow-up
description: Percentage of participants with detectable tenofovir levels from vaginal samples at 12 months of follow-up. All drug levels below limit of quantification were considered to be undetectable.
measure: Product Acceptability
time frame: At study completion, up to 28 months
description: This is the number of participants who reported that they liked the study product. The questionnaire was administered at study exit, therefore participants who were loss to follow-up and those who died could not complete the questionnaire.
arm group label: Intervention
arm group type: Experimental
description: 1% tenofovir gel provision through a public sector family planning services with 2-3 monthly provision and monitoring and the use of Quality Improvement methodology to promote reliable service delivery
arm group label: Control
arm group type: Active Comparator
description: monthly 1% tenofovir gel provision and monitoring through CAPRISA research clinics
intervention type: Drug
intervention name: 1% tenofovir gel
description: Participants will be randomized to receive 1% tenofovir gel through either:
Public sector family planning services with 2-3 monthly provision and monitoring of 1% tenofovir gel and the use of QI methodology to promote reliable service delivery (intervention arm), or
The CAPRISA research clinics with monthly provision and monitoring of 1% tenofovir gel (control arm).
arm group label: Control
arm group label: Intervention
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Quarraisha Abdool Karim, PhD
role: Principal Investigator
affiliation: Centre for the AIDS Programme of Research in South Africa
facility: 
facility: 
country: South Africa
url: http://www.caprisa.org
description: Centre for the AIDS Programme of Research in South Africa web site
citation: Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19. Erratum In: Science. 2011 Jul 29;333(6042):524.
PMID: 20643915
responsible party type: Principal Investigator
investigator affiliation: Centre for the AIDS Programme of Research in South Africa
investigator full name: Dr Quarraisha Abdool Karim
investigator title: Associate Scientific Director
mesh term: Tenofovir
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The 2-3 monthly intervals between clinic appointments in the control arm is likely to introduce recall bias in this arm, unlike the monthly intervals in the intervention arm.
point of contact: 