<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/NCT02263326</url>
  </required_header>
  <id_info>
    <org_study_id>ASPIRE</org_study_id>
    <nct_id>NCT02263326</nct_id>
  </id_info>
  <brief_title>Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure</brief_title>
  <acronym>ASPIRE</acronym>
  <official_title>Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Babafemi Taiwo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ViiV Healthcare</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      HIV-1 infected subjects with CD4 nadir &gt; 200 cells/mm3, no history of virologic failure and&#xD;
      plasma HIV RNA &lt;50 copies/mL for at least 48 weeks while on any United States Department of&#xD;
      Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen&#xD;
      will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their&#xD;
      current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as&#xD;
      confirmed plasma HIV-1 RNA &gt; 50 copies/mL before or at Week 24&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      DESIGN HIV-1 infected subjects with CD4 nadir &gt; 200 cells/mm3, no history of virologic&#xD;
      failure and plasma HIV RNA &lt;50 copies/mL for at least 48 weeks while on any United States&#xD;
      Department of Health and Human Services (DHHS) recommended or alternative three-drug&#xD;
      antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or&#xD;
      continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic&#xD;
      failure defined as confirmed plasma HIV-1 RNA &gt; 50 copies/mL before or at Week 24&#xD;
&#xD;
      All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count,&#xD;
      hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who&#xD;
      experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual&#xD;
      viremia.&#xD;
&#xD;
      DURATION 48 weeks&#xD;
&#xD;
      SAMPLE SIZE 90 subjects&#xD;
&#xD;
      POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir &gt; 200 cells/mm3,&#xD;
      no baseline resistance, no history of virologic failure, and HIV RNA &lt;50 copies/mL for at&#xD;
      least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug&#xD;
      regimen&#xD;
&#xD;
      REGIMEN Subjects will be randomized (1:1) to:&#xD;
&#xD;
      Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily OR Arm 2: Continue current DHHS&#xD;
      recommended or alternative three-drug antiretroviral regimen&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Participants With Treatment Failure</measure>
    <time_frame>24 weeks</time_frame>
    <description>Proportion of participants with treatment failure (defined as virologic failure (HIV RNA &gt;50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Virologic Success</measure>
    <time_frame>48 weeks</time_frame>
    <description>Proportion of participants with virologic success (&lt;50 copies/mL) based on FDA snapshot definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CD4 Count From Baseline to Week 48</measure>
    <time_frame>Baseline and 48 weeks</time_frame>
    <description>Change in CD4 count between arms will be presented in the attached statistical analysis table</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Total Cholesterol From Baseline to Week 48</measure>
    <time_frame>Baseline and 48 weeks</time_frame>
    <description>Change in Total Cholesterol between arms will be presented in the attached statistical analysis table</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in LDL Cholesterol From Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
    <description>Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Creatinine Clearance From Baseline to Week 48</measure>
    <time_frame>Baseline and Week 48</time_frame>
    <description>Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug Resistance Associated Mutations</measure>
    <time_frame>48 weeks</time_frame>
    <description>Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Residual Viremia by HIV-1 Single-copy Assay</measure>
    <time_frame>48 weeks</time_frame>
    <description>Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>HIV Infection</condition>
  <arm_group>
    <arm_group_label>dolutegravir plus lamivudine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dolutegravir 50 mg plus lamivudine 300 mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continue current ART regimen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dolutegravir</intervention_name>
    <description>50 mg tablet by mouth once daily for 48 weeks</description>
    <arm_group_label>dolutegravir plus lamivudine</arm_group_label>
    <other_name>TIVICAY, DTG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lamivudine</intervention_name>
    <description>300 mg tablet by mouth once daily for 48 weeks</description>
    <arm_group_label>dolutegravir plus lamivudine</arm_group_label>
    <other_name>EPIVIR, 3TC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continue current antiretroviral regimen</intervention_name>
    <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
    <arm_group_label>Continue current ART regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 Infection&#xD;
&#xD;
          -  HIV-1 RNA &lt;50 copies/mL on all measurements within 48 weeks prior to study entry while&#xD;
             on any DHHS recommended or alternative three-drug antiretroviral regimen. (A history&#xD;
             of switching for simplification and/or tolerability is allowed. At least two&#xD;
             measurements within the previous 48 weeks are required prior to study screening.)&#xD;
&#xD;
          -  No history of virologic failure, defined as consecutive HIV RNA &gt; 50 copies/mL after&#xD;
             12 months of initiating ART. An isolated (non-consecutive) HIV RNA &gt; 50 copies/mL (but&#xD;
             less than 400 copies/mL) is permitted after 12 months of initiating ART but not in the&#xD;
             48-week window prior to study entry.&#xD;
&#xD;
          -  Screening plasma HIV RNA &lt; 20 copies/mL using the COBAS AmpliPrep/COBAS TaqMan HIV-1&#xD;
             Test V2.0, obtained within 45 days prior to study entry&#xD;
&#xD;
          -  Nadir CD4 count &gt;200 cells/mm&#xD;
&#xD;
          -  Pretreatment genotype documenting no mutations in the protease or reverse&#xD;
             transcriptase genes&#xD;
&#xD;
          -  No known resistance to integrase inhibitors&#xD;
&#xD;
          -  Laboratory values obtained within 45 days prior to study entry:&#xD;
&#xD;
        ANC &gt;750 Hemoglobin &gt;10 g/dL Platelets &gt;50,000 Calculated creatinine clearance (CrCl) &gt;50&#xD;
        mL/min&#xD;
&#xD;
          -  Negative serum or urine pregnancy test&#xD;
&#xD;
          -  Men and women age greater or equal to 18 years.&#xD;
&#xD;
          -  Ability to continue current regimen (i.e, have uninterrupted access)&#xD;
&#xD;
          -  No evidence of chronic hepatitis B&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Serious illness or AIDS-related complication within 21 days of screening requiring&#xD;
             systemic treatment and/or hospitalization&#xD;
&#xD;
          -  Treatment within 30 days prior to study entry with immune modulators&#xD;
&#xD;
          -  Vaccination within 7 days&#xD;
&#xD;
          -  Active HCV treatment or anticipated need for treatment within study period. (HCV&#xD;
             infection alone is not exclusionary)&#xD;
&#xD;
          -  Unstable liver disease or severe hepatic impairment&#xD;
&#xD;
          -  Known allergy or hypersensitivity to DTG or lamivudine.&#xD;
&#xD;
          -  Active drug or alcohol use or dependence that could interfere with adherence to study&#xD;
             requirements&#xD;
&#xD;
          -  ALT (alanine aminotransferase) &gt;5 x ULN (upper limit of normal) OR ALT &gt;3 x ULN and&#xD;
             total bilirubin &gt;1.5 x ULN (with 35% direct bilirubin)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Babafemi Taiwo, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornell University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <results_first_submitted>August 24, 2018</results_first_submitted>
  <results_first_submitted_qc>November 8, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 13, 2018</results_first_posted>
  <last_update_submitted>October 10, 2019</last_update_submitted>
  <last_update_submitted_qc>October 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Babafemi Taiwo</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lamivudine</mesh_term>
    <mesh_term>Dolutegravir</mesh_term>
    <mesh_term>Anti-Retroviral Agents</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 25, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT02263326/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dolutegravir Plus Lamivudine</title>
          <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
        </group>
        <group group_id="P2">
          <title>Continue Current ART Regimen</title>
          <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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>
      <group_list>
        <group group_id="B1">
          <title>Dolutegravir Plus Lamivudine</title>
          <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
        </group>
        <group group_id="B2">
          <title>Continue Current ART Regimen</title>
          <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</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="44"/>
            <count group_id="B2" value="45"/>
            <count group_id="B3" value="89"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46" lower_limit="37" upper_limit="56"/>
                    <measurement group_id="B2" value="50" lower_limit="41" upper_limit="53"/>
                    <measurement group_id="B3" value="47" lower_limit="38" upper_limit="54"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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>
              <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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="52"/>
                  </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>CD4 Cell Count</title>
          <units>cells/mm3</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="694" lower_limit="533" upper_limit="1034"/>
                    <measurement group_id="B2" value="646" lower_limit="380" upper_limit="819"/>
                    <measurement group_id="B3" value="680" lower_limit="498" upper_limit="927"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time on Antiretroviral Therapy</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.28" lower_limit="3.81" upper_limit="7.49"/>
                    <measurement group_id="B2" value="6.03" lower_limit="3.72" upper_limit="7.44"/>
                    <measurement group_id="B3" value="5.7" lower_limit="3.72" upper_limit="7.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Current ART Regimen</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Integrase Inhibitor</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Protease Inhibitor</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Nonnucleoside reverse transcriptase inhibitor</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants With Treatment Failure</title>
        <description>Proportion of participants with treatment failure (defined as virologic failure (HIV RNA &gt;50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen</description>
        <time_frame>24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Treatment Failure</title>
          <description>Proportion of participants with treatment failure (defined as virologic failure (HIV RNA &gt;50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0682"/>
                    <measurement group_id="O2" value="0.0667"/>
                  </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>A sample size of 41 participants per arm provided 80% power to show noninferiority of DTG/3TC to cART based on a 12% noninferiority margin, assuming an estimated treatment failure rate of 5% per arm by week 24 and 5% 1-sided type I error rate.</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>We considered DTG/3TC was noninferior to cART if the 90% confidence interval for the difference in proportions, calculated with Miettinen-Nurminen (score) confidence limits, excluded the 12% noninferiority margin.</non_inferiority_desc>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>0.0015</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.098</ci_lower_limit>
            <ci_upper_limit>0.102</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Virologic Success</title>
        <description>Proportion of participants with virologic success (&lt;50 copies/mL) based on FDA snapshot definition</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Virologic Success</title>
          <description>Proportion of participants with virologic success (&lt;50 copies/mL) based on FDA snapshot definition</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9091"/>
                    <measurement group_id="O2" value="0.8889"/>
                  </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>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>The difference in virologic outcomes based on the FDA snapshot algorithm at week 48 (HIV RNA &lt;50 copies/mL) was compared between arms, with 95% confidence intervals.</non_inferiority_desc>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>0.020</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.126</ci_lower_limit>
            <ci_upper_limit>0.165</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in CD4 Count From Baseline to Week 48</title>
        <description>Change in CD4 count between arms will be presented in the attached statistical analysis table</description>
        <time_frame>Baseline and 48 weeks</time_frame>
        <population>Population with CD4 count data available at baseline and week 48</population>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Change in CD4 Count From Baseline to Week 48</title>
          <description>Change in CD4 count between arms will be presented in the attached statistical analysis table</description>
          <population>Population with CD4 count data available at baseline and week 48</population>
          <units>cells/mm^3</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39" lower_limit="-71" upper_limit="188"/>
                    <measurement group_id="O2" value="28" lower_limit="-36" upper_limit="83"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.866</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Cholesterol From Baseline to Week 48</title>
        <description>Change in Total Cholesterol between arms will be presented in the attached statistical analysis table</description>
        <time_frame>Baseline and 48 weeks</time_frame>
        <population>Population with total cholesterol data available at baseline and week 48</population>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Cholesterol From Baseline to Week 48</title>
          <description>Change in Total Cholesterol between arms will be presented in the attached statistical analysis table</description>
          <population>Population with total cholesterol data available at baseline and week 48</population>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="-31" upper_limit="31"/>
                    <measurement group_id="O2" value="-1" lower_limit="-13" upper_limit="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>Other</non_inferiority_type>
            <p_value>0.613</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in LDL Cholesterol From Baseline to Week 48</title>
        <description>Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table</description>
        <time_frame>Baseline and Week 48</time_frame>
        <population>Population with LDL cholesterol data available at baseline and week 48</population>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Change in LDL Cholesterol From Baseline to Week 48</title>
          <description>Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table</description>
          <population>Population with LDL cholesterol data available at baseline and week 48</population>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="-19" upper_limit="27"/>
                    <measurement group_id="O2" value="-3" lower_limit="-16" upper_limit="10"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.420</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Creatinine Clearance From Baseline to Week 48</title>
        <description>Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table</description>
        <time_frame>Baseline and Week 48</time_frame>
        <population>Population with creatinine clearance data available at baseline and week 48</population>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Creatinine Clearance From Baseline to Week 48</title>
          <description>Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table</description>
          <population>Population with creatinine clearance data available at baseline and week 48</population>
          <units>ml/min</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4" lower_limit="-14" upper_limit="4"/>
                    <measurement group_id="O2" value="0" lower_limit="-6" upper_limit="5"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.074</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Drug Resistance Associated Mutations</title>
        <description>Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Drug Resistance Associated Mutations</title>
          <description>Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Residual Viremia by HIV-1 Single-copy Assay</title>
        <description>Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis</description>
        <time_frame>48 weeks</time_frame>
        <population>Participants with HIV-1 single copy assays performed at baseline and week 48 timepoints</population>
        <group_list>
          <group group_id="O1">
            <title>Dolutegravir Plus Lamivudine</title>
            <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>Continue Current ART Regimen</title>
            <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
          </group>
        </group_list>
        <measure>
          <title>Residual Viremia by HIV-1 Single-copy Assay</title>
          <description>Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis</description>
          <population>Participants with HIV-1 single copy assays performed at baseline and week 48 timepoints</population>
          <units>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="36"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="7.0"/>
                    <measurement group_id="O2" value="4.2" spread="6.0"/>
                  </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>Other</non_inferiority_type>
            <p_value>0.76</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.0</ci_lower_limit>
            <ci_upper_limit>4.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>48 weeks</time_frame>
      <desc>After study entry, all laboratory values greater than or equal to Grade 3, any laboratory values that lead to a change in study treatment, and all renal, liver function tests, and lipid values, regardless of grade, were reported. All Grade ≥3 signs/symptoms, any signs/symptoms regardless of grade that lead to a change in treatment, or that meet Expedited Adverse Event (EAE), SAE, or ICH guidelines.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dolutegravir Plus Lamivudine</title>
          <description>dolutegravir 50 mg plus lamivudine 300 mg once daily&#xD;
dolutegravir: 50 mg tablet by mouth once daily for 48 weeks&#xD;
lamivudine: 300 mg tablet by mouth once daily for 48 weeks</description>
        </group>
        <group group_id="E2">
          <title>Continue Current ART Regimen</title>
          <description>Continue current DHHS recommended or alternative three-drug antiretroviral regimen&#xD;
Continue current antiretroviral regimen: Continue current DHHS recommended or alternative three-drug antiretroviral regimen</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Grade 4 myocardial infarctions</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Grade 4 viral syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>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="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Grade 3 bilirubinemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="45"/>
              </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>
    <point_of_contact>
      <name_or_title>Babafemi Taiwo</name_or_title>
      <organization>Northwestern University</organization>
      <phone>312-695-5085</phone>
      <email>b-taiwo@northwestern.edu</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/NCT02263326
org study id: ASPIRE
nct id: NCT02263326
lead sponsor: 
collaborator: 
has dmc: Yes
HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and
      plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of
      Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen
      will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their
      current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as
      confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24
DESIGN HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic
      failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States
      Department of Health and Human Services (DHHS) recommended or alternative three-drug
      antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or
      continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic
      failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24

      All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count,
      hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who
      experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual
      viremia.

      DURATION 48 weeks

      SAMPLE SIZE 90 subjects

      POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir > 200 cells/mm3,
      no baseline resistance, no history of virologic failure, and HIV RNA <50 copies/mL for at
      least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug
      regimen

      REGIMEN Subjects will be randomized (1:1) to:

      Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily OR Arm 2: Continue current DHHS
      recommended or alternative three-drug antiretroviral regimen
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Participants With Treatment Failure
time frame: 24 weeks
description: Proportion of participants with treatment failure (defined as virologic failure (HIV RNA >50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen
measure: Proportion of Participants With Virologic Success
time frame: 48 weeks
description: Proportion of participants with virologic success (<50 copies/mL) based on FDA snapshot definition
measure: Change in CD4 Count From Baseline to Week 48
time frame: Baseline and 48 weeks
description: Change in CD4 count between arms will be presented in the attached statistical analysis table
measure: Change in Total Cholesterol From Baseline to Week 48
time frame: Baseline and 48 weeks
description: Change in Total Cholesterol between arms will be presented in the attached statistical analysis table
measure: Change in LDL Cholesterol From Baseline to Week 48
time frame: Baseline and Week 48
description: Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table
measure: Change in Creatinine Clearance From Baseline to Week 48
time frame: Baseline and Week 48
description: Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table
measure: Drug Resistance Associated Mutations
time frame: 48 weeks
description: Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure
measure: Residual Viremia by HIV-1 Single-copy Assay
time frame: 48 weeks
description: Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis
arm group label: dolutegravir plus lamivudine
arm group type: Experimental
description: dolutegravir 50 mg plus lamivudine 300 mg once daily
arm group label: Continue current ART regimen
arm group type: Active Comparator
description: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
intervention type: Drug
intervention name: dolutegravir
description: 50 mg tablet by mouth once daily for 48 weeks
arm group label: dolutegravir plus lamivudine
other name: TIVICAY, DTG
intervention type: Drug
intervention name: lamivudine
description: 300 mg tablet by mouth once daily for 48 weeks
arm group label: dolutegravir plus lamivudine
other name: EPIVIR, 3TC
intervention type: Drug
intervention name: Continue current antiretroviral regimen
description: Continue current DHHS recommended or alternative three-drug antiretroviral regimen
arm group label: Continue current ART regimen
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Babafemi Taiwo, MBBS
role: Principal Investigator
affiliation: Northwestern University
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country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Northwestern University
investigator full name: Babafemi Taiwo
investigator title: Professor
mesh term: HIV Infections
mesh term: Lamivudine
mesh term: Dolutegravir
mesh term: Anti-Retroviral Agents
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 