A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: dolutegravir
Intervention description: 50 mg twice daily
Intervention MeSH terms: Dolutegravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 183.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GSK1349572; resistance to raltegravir or elvitegravir; Integrase inhibitor; ART-experienced; dolutegravir

Summary:

      The purpose of this trial is to assess the antiviral activity and safety of a dolutegravir
      (DTG) containing regimen in HIV-1 infected, antiretroviral therapy (ART)-experienced adults
      with current or historical failure on an integrase inhibitor (INI) containing regimen. The
      study will assess DTG 50mg twice daily administered initially with the current failing ART
      regimen but then with an optimised background ART regimen (OBR) after Day 7. The first
      analyses will be conducted after the last subject enrolled has completed 24 weeks. Subjects
      may remain on study after Week 24.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Screening plasma HIV-1 RNA ≥500 copies/mL

          -  ART-experienced, INI-experienced, DTG naïve

          -  Experienced virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen

          -  The subject's HIV-1 shows resistance to RAL or ELV at Screening or at prior time point
             of virological failure on RAL or ELV

          -  Documented resistance to at least one drug from each of three or more of all approved
             classes of ART

          -  Be able to receive at least one fully active drug as part of the OBR from Day 8

          -  Women capable of becoming pregnant must use appropriate contraception during the study
             (as defined by the protocol)

          -  Willing and able to understand and provide signed and dated written informed consent
             prior to Screening.

        Exclusion Criteria:

          -  Women who are pregnant or breast feeding

          -  An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not
             requiring systemic therapy or CD4+ <200c/mm3)

          -  Moderate to severe hepatic impairment as defined by Child-Pugh classification

          -  Anticipated need for HCV therapy during the first 24 weeks of the study

          -  Recent history of any upper or lower gastrointestinal bleed, with the exception of
             anal or rectal bleeding

          -  Allergy or intolerance to the study drugs or their components or drugs of their class

          -  Malignancy within the past 6 months

          -  Treatment with an HIV-1 therapeutic vaccine within 90 days of Screening

          -  Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any
             immunomodulator within 28 days of Screening

          -  Treatment with any agent, other than licensed ART, with documented activity against
             HIV-1 in vitro within 28 days of first dose of investigational product

          -  Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine
             may be used if coadministered with lopinivir/ritonavir or darunavir/ritonavir)

          -  Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within
             28 days prior to Screening

          -  Verified Grade 4 laboratory abnormality at Screening

          -  ALT> 5 times the upper limit of normal (ULN) at Screening

          -  ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening