<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/NCT01694420</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00035447</org_study_id>
    <secondary_id>IN-US-236-0124</secondary_id>
    <nct_id>NCT01694420</nct_id>
  </id_info>
  <brief_title>Treatment of Acute HIV Infection With Quad Fixed-dose Combination (FDC) Tablet</brief_title>
  <acronym>PHI04</acronym>
  <official_title>Treatment of Acute HIV Infection With the Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate, A Pilot Study of Response to Therapy and HIV Pathogenesis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, single arm, 48-week open-label study of FDC ELV/COBI/FTC/TDF&#xD;
      [Stribild] in acute HIV infection. Study sites will be members of the Duke-UNC Acute HIV&#xD;
      Infection Study Consortium. Participants will be enrolled for 96 weeks. Clinical care and&#xD;
      study drug (ELV/COBI/FTC/TDF) will be provided for the first 48 weeks. After week 48,&#xD;
      clinical care but not study drug will be provided through week 96. A study participant&#xD;
      suppressed at week 48 can continue on FDC ELV/COBI/FTC/TDF.&#xD;
&#xD;
      The primary hypothesis is that once daily fixed-dose combination elvitegravir (ELV),&#xD;
      cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) will rapidly&#xD;
      reduce viral replication to &lt;50 copies RNA/ml in participants with acute HIV infection. The&#xD;
      secondary hypotheses to be considered are 1) virologic response rates as measured by plasma&#xD;
      HIV RNA levels will be non-inferior or superior to a historical group of participants from&#xD;
      the PHI cohort treated with EFV/FTC/TDF, 2) compared to historical controls treated with&#xD;
      EFV/FTC/TDF, plasma HIV RNA will decrease more rapidly in PHI participants treated with&#xD;
      ELV/COBI/FTC/TDF, 3) compared to historical controls treated with EFV/FTC/TDF, immune&#xD;
      activation as measured by the proportion CD4+ and CD8+ cells expressing HLA-DR and CD38+ will&#xD;
      decrease more rapidly in PHI participants treated with ELV/COBI/FTC/TDF, 4)in a subset of&#xD;
      participants samples will be obtained from compartments such as the gastrointestinal tract,&#xD;
      and lymphoid tissues to assess changes over time in parameters such as HIV-1 RNA, immunologic&#xD;
      responses to HIV, and tissue and anatomic reservoirs. We hypothesize that treatment with the&#xD;
      ELV/COBI/FTC/TDF will demonstrate improved viral clearance in these compartments as compared&#xD;
      to historical controls treated with EFV/FTC/TDF. 5) in a subset of participants who remain&#xD;
      suppressed on therapy, resting CD4 cells with replication-competent HIV-1 (latent reservoir)&#xD;
      will be quantitated and compared to similar measurements in PHI participants treated with&#xD;
      EFV/FTC/TDF. In addition, we will compare these results to those measured in HIV-1 infected&#xD;
      participants treated and 6) ELV/COBI/FTC/TDF will be well tolerated, and the proportion of&#xD;
      participants who require treatment modification will be less than that observed in&#xD;
      participants treated with EFV/FTC/TDF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      None desired&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With a Viral Load Measurement of &lt;200 Copies/mL at Week 24</measure>
    <time_frame>24 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Virologic Efficacy of the Fixed Dose Combination (FDC) ELV/COBI/FTC/TDF Given Once Daily to Participants With Acute HIV Infection as Determined by the Proportion of Treated Participants With HIV-1 RNA to &lt;50 Copies/mL at Week 48</measure>
    <time_frame>48 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune Activation as Measured by the Proportion of CD4+ and CD8+ Cells Expressing HLA-DR and CD38+</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Virologic Decline in the First 48 Weeks of Treatment Comparing FDC ELV/COBI/FTC/TDF to FDC EFV/FTC/TDF</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Participants With Grade 3 or Grade 4 Adverse Events</measure>
    <time_frame>48 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Adverse Events Related to Study Drug</measure>
    <time_frame>48 weeks</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Quad FDC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>(FDC) ELV/COBI/FTC/TDF</intervention_name>
    <description>Antiretroviral treatment</description>
    <arm_group_label>Quad FDC</arm_group_label>
    <other_name>STRIBILD</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Acute HIV infection is defined as:&#xD;
&#xD;
          1. A positive 4th generation HIV Ag/Ab Combination Assay and HIV RNA (NAAT or viral load)&#xD;
             and one of the following within 30 days of study entry:&#xD;
&#xD;
               -  a negative HIV rapid test&#xD;
&#xD;
               -  negative/indeterminate Western Blot&#xD;
&#xD;
             OR&#xD;
&#xD;
          2. A negative or indeterminate HIV antibody, antigen, or nucleic acid amplification test&#xD;
             (NAAT) and any one of the following within 30 days of study entry:&#xD;
&#xD;
               -  A detectable HIV nucleic acid in blood confirmed by a second NAAT&#xD;
&#xD;
               -  Positive p24 antigen&#xD;
&#xD;
               -  A positive HIV antibody test according to standard criteria obtained within 45&#xD;
                  days after an initial negative or indeterminate HIV antibody, antigen, or nucleic&#xD;
                  acid amplification.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Acute HIV Infection (as defined above) within 30 days of study entry.&#xD;
&#xD;
          2. Age &gt;18 years.&#xD;
&#xD;
          3. ART-naive (&lt;14 days of previous antiretroviral treatment. Exceptions are:&#xD;
             Post-exposure prophylaxis (PEP) if participant was documented as HIV-negative at least&#xD;
             3 months after completion of PEP.&#xD;
&#xD;
          4. Lab values within 30 days prior to study entry:&#xD;
&#xD;
               1. Absolute neutrophil count &gt;500/mm3&#xD;
&#xD;
               2. Hemoglobin &gt; 8.5 g/dL for men and &gt; 8.0 g/dL for women&#xD;
&#xD;
               3. Platelet count &gt;50,000/mm3&#xD;
&#xD;
               4. AST (SGOT)&gt; .2.5 x ULN&#xD;
&#xD;
               5. ALT (SGPT)&gt; .2.5 x ULN&#xD;
&#xD;
               6. Total bilirubin &lt;2.5 x ULN&#xD;
&#xD;
               7. Calculated creatinine clearance (Cockcroft-Gault formula) &gt; 70mL/min:&#xD;
&#xD;
          5. For women of reproductive potential, a negative pregnancy test within 72 hours prior&#xD;
             to initiating antiretroviral study medications. Reproductive potential is defined as&#xD;
             females who have reached menarche and have not been post-menopausal for at least 24&#xD;
             consecutive months, or have not undergone surgical sterilization.&#xD;
&#xD;
          6. Female study participants must use a reliable form of barrier contraception, such as a&#xD;
             condom, even if they also use other methods of birth control. All participants must&#xD;
             continue to use contraception for 12 weeks after stopping study medications.&#xD;
             Acceptable methods of barrier contraception include: condoms (male or female),&#xD;
             diaphragm, or cervical cap. These can be used alone or in tandem with hormonal or IUD&#xD;
             method.&#xD;
&#xD;
          7. Ability and willingness of participant to give written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who are pregnant or breast-feeding.&#xD;
&#xD;
          2. Women with a positive pregnancy test prior to study drug administration.&#xD;
&#xD;
          3. Men who have sex with women, and women of reproductive potential unwilling or unable&#xD;
             to use an acceptable, reliable barrier method of contraception for the entire study&#xD;
             period and 12 weeks afterwards.&#xD;
&#xD;
          4. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine,&#xD;
             systemic cytotoxic chemotherapy, or investigational therapy within 30 days of study&#xD;
             entry (Prednisone 10 mg QD or less is permitted.&#xD;
&#xD;
          5. Known allergy/sensitivity to study drugs&#xD;
&#xD;
          6. Difficulty swallowing pills&#xD;
&#xD;
          7. Inability to communicate effectively with study personnel&#xD;
&#xD;
          8. Incarceration; prisoner recruitment and participation are not permitted&#xD;
&#xD;
          9. Active drug or alcohol use that, in the opinion of the site investigator, would&#xD;
             interfere with participation in the study&#xD;
&#xD;
         10. Any active psychiatric illness that, in the opinion of the investigator, could&#xD;
             confound the analysis of the neurological examination or neuropsychological test&#xD;
             results&#xD;
&#xD;
         11. Active brain infection (except for HIV-1), brain neoplasm, space-occupying brain&#xD;
             lesion requiring acute or chronic therapy&#xD;
&#xD;
         12. Serious illness requiring systemic treatment and/or hospitalization until patient&#xD;
             either completes therapy or is clinically stable on therapy for at least 7 days prior&#xD;
             to study entry&#xD;
&#xD;
         13. Known cardiac conduction disease&#xD;
&#xD;
         14. Prior treatment with any other experimental drug within 30 days of initiating study&#xD;
             treatment&#xD;
&#xD;
         15. Unable to discontinue any current medications that are excluded during study treatment&#xD;
&#xD;
         16. Life expectancy less than twelve months&#xD;
&#xD;
         17. Acute Viral Hepatitis, including, but not limited to, Hepatitis A, B, or C&#xD;
&#xD;
         18. Chronic Hepatitis B Infection documented by a detectable serum Hepatitis B surface&#xD;
             antigen (HBsAg) or plasma HBV DNA&#xD;
&#xD;
         19. Calculated creatinine clearance (Cockcroft-Gault formula) &lt;70mL/min&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mehri McKellar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UNC at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gay CL, Mayo AJ, Mfalila CK, Chu H, Barry AC, Kuruc JD, McGee KS, Kerkau M, Sebastian J, Fiscus SA, Margolis DM, Hicks CB, Ferrari G, Eron JJ; Duke-UNC Acute HIV Infection Consortium. Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection. AIDS. 2011 Apr 24;25(7):941-9. doi: 10.1097/QAD.0b013e3283463c07.</citation>
    <PMID>21487250</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <results_first_submitted>October 31, 2016</results_first_submitted>
  <results_first_submitted_qc>October 31, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 23, 2016</results_first_posted>
  <last_update_submitted>March 14, 2017</last_update_submitted>
  <last_update_submitted_qc>March 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants for this study are recruited from AHI participants referred to our ID clinics. Referrals are generated from the NC STAT Program and from clinical diagnoses made by both internal and external health care clinics.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Quad FDC</title>
          <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </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="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Quad FDC</title>
          <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="33"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Viral Load Measurement of &lt;200 Copies/mL at Week 24</title>
        <time_frame>24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quad FDC</title>
            <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Viral Load Measurement of &lt;200 Copies/mL at Week 24</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Virologic Efficacy of the Fixed Dose Combination (FDC) ELV/COBI/FTC/TDF Given Once Daily to Participants With Acute HIV Infection as Determined by the Proportion of Treated Participants With HIV-1 RNA to &lt;50 Copies/mL at Week 48</title>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quad FDC</title>
            <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Virologic Efficacy of the Fixed Dose Combination (FDC) ELV/COBI/FTC/TDF Given Once Daily to Participants With Acute HIV Infection as Determined by the Proportion of Treated Participants With HIV-1 RNA to &lt;50 Copies/mL at Week 48</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immune Activation as Measured by the Proportion of CD4+ and CD8+ Cells Expressing HLA-DR and CD38+</title>
        <time_frame>48 weeks</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Quad FDC</title>
            <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Immune Activation as Measured by the Proportion of CD4+ and CD8+ Cells Expressing HLA-DR and CD38+</title>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Virologic Decline in the First 48 Weeks of Treatment Comparing FDC ELV/COBI/FTC/TDF to FDC EFV/FTC/TDF</title>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quad FDC</title>
            <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Virologic Decline in the First 48 Weeks of Treatment Comparing FDC ELV/COBI/FTC/TDF to FDC EFV/FTC/TDF</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HIV RNA &lt;200 copies/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26" lower_limit="7" upper_limit="132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HIV RNA &lt;50 copies/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54" lower_limit="12" upper_limit="251"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Study data compared to data as cited in PubMed ID: 21487250</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Grade 3 or Grade 4 Adverse Events</title>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quad FDC</title>
            <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade 3 or Grade 4 Adverse Events</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Adverse Events Related to Study Drug</title>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quad FDC</title>
            <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events Related to Study Drug</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Quad FDC</title>
          <description>FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks&#xD;
(FDC) ELV/COBI/FTC/TDF: Antiretroviral treatment</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE version 4</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Decreased neutrophils</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated cholesterol</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Shigella colitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>stomach cramping</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Feeling of air stuck in throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Alteration in taste</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>thigh weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated ALT</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Elevated AST</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Elevated lipase</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Chest wall injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased comprehension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Short term memory loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated creatinine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Disseminated itching</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>thinning hair</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Elevated BP during leukapheresis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Tingling around lips during leukaphersis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
              </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>Mehri McKeller, MD</name_or_title>
      <organization>Duke University Medical Center</organization>
      <phone>919-668-0242</phone>
      <email>kara.mcgee@duke.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/NCT01694420
org study id: Pro00035447
secondary id: IN-US-236-0124
nct id: NCT01694420
lead sponsor: 
has dmc: No
This is a multicenter, single arm, 48-week open-label study of FDC ELV/COBI/FTC/TDF
      [Stribild] in acute HIV infection. Study sites will be members of the Duke-UNC Acute HIV
      Infection Study Consortium. Participants will be enrolled for 96 weeks. Clinical care and
      study drug (ELV/COBI/FTC/TDF) will be provided for the first 48 weeks. After week 48,
      clinical care but not study drug will be provided through week 96. A study participant
      suppressed at week 48 can continue on FDC ELV/COBI/FTC/TDF.

      The primary hypothesis is that once daily fixed-dose combination elvitegravir (ELV),
      cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) will rapidly
      reduce viral replication to <50 copies RNA/ml in participants with acute HIV infection. The
      secondary hypotheses to be considered are 1) virologic response rates as measured by plasma
      HIV RNA levels will be non-inferior or superior to a historical group of participants from
      the PHI cohort treated with EFV/FTC/TDF, 2) compared to historical controls treated with
      EFV/FTC/TDF, plasma HIV RNA will decrease more rapidly in PHI participants treated with
      ELV/COBI/FTC/TDF, 3) compared to historical controls treated with EFV/FTC/TDF, immune
      activation as measured by the proportion CD4+ and CD8+ cells expressing HLA-DR and CD38+ will
      decrease more rapidly in PHI participants treated with ELV/COBI/FTC/TDF, 4)in a subset of
      participants samples will be obtained from compartments such as the gastrointestinal tract,
      and lymphoid tissues to assess changes over time in parameters such as HIV-1 RNA, immunologic
      responses to HIV, and tissue and anatomic reservoirs. We hypothesize that treatment with the
      ELV/COBI/FTC/TDF will demonstrate improved viral clearance in these compartments as compared
      to historical controls treated with EFV/FTC/TDF. 5) in a subset of participants who remain
      suppressed on therapy, resting CD4 cells with replication-competent HIV-1 (latent reservoir)
      will be quantitated and compared to similar measurements in PHI participants treated with
      EFV/FTC/TDF. In addition, we will compare these results to those measured in HIV-1 infected
      participants treated and 6) ELV/COBI/FTC/TDF will be well tolerated, and the proportion of
      participants who require treatment modification will be less than that observed in
      participants treated with EFV/FTC/TDF.
None desired
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With a Viral Load Measurement of <200 Copies/mL at Week 24
time frame: 24 weeks
measure: Virologic Efficacy of the Fixed Dose Combination (FDC) ELV/COBI/FTC/TDF Given Once Daily to Participants With Acute HIV Infection as Determined by the Proportion of Treated Participants With HIV-1 RNA to <50 Copies/mL at Week 48
time frame: 48 weeks
measure: Immune Activation as Measured by the Proportion of CD4+ and CD8+ Cells Expressing HLA-DR and CD38+
time frame: 48 weeks
measure: Rate of Virologic Decline in the First 48 Weeks of Treatment Comparing FDC ELV/COBI/FTC/TDF to FDC EFV/FTC/TDF
time frame: 48 weeks
measure: Number of Participants With Grade 3 or Grade 4 Adverse Events
time frame: 48 weeks
measure: Number of Participants With Adverse Events Related to Study Drug
time frame: 48 weeks
arm group label: Quad FDC
arm group type: Experimental
description: FDC elvitegravir + cobicistat + tenofovir + emtricitabine STR once daily for 48 weeks
intervention type: Drug
intervention name: (FDC) ELV/COBI/FTC/TDF
description: Antiretroviral treatment
arm group label: Quad FDC
other name: STRIBILD
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Mehri McKellar, MD
role: Principal Investigator
affiliation: Duke University
facility: 
facility: 
country: United States
citation: Gay CL, Mayo AJ, Mfalila CK, Chu H, Barry AC, Kuruc JD, McGee KS, Kerkau M, Sebastian J, Fiscus SA, Margolis DM, Hicks CB, Ferrari G, Eron JJ; Duke-UNC Acute HIV Infection Consortium. Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection. AIDS. 2011 Apr 24;25(7):941-9. doi: 10.1097/QAD.0b013e3283463c07.
PMID: 21487250
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 