Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: dolutegravir 50 mg OAD; darunavir 800mg OAD; ritonavir 100mg OAD
Intervention description: 1 x 50 mg tablet OAD; 2 x 400mg tablets OAD; 1 x 100mg tablet OAD
Intervention MeSH terms: Ritonavir; Darunavir; Dolutegravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 488.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ritonavir; HIV; HAART; darunavir; antiretroviral; dolutegravir; GSK1349572

Summary:

      This study will be conducted in approximately 468 HIV-1 infected antiretroviral therapy
      (ART)-naïve subjects. Subjects will be randomized 1:1 to receive dolutegravir (DTG) 50 mg
      once daily (approximately 234 subjects) or darunavir/ritonavir (DRV/r) 800 mg/100 mg once
      daily (approximately 234 subjects), each in combination with fixed-dose dual nucleoside
      reverse transriptase inhibitor (NRTI) therapy (either abacavir/lamivudine (ABC/3TC) or
      tenofovir/emtricitabine (TDF/FTC). Subjects will be stratified by screening HIV-1 RNA and
      background NRTI selection. The primary analysis will take place after the last subject
      completes 48 weeks on therapy; an additional analysis will be conducted after the last
      subject completes Week 96 on study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected adults greater than or equal to 18 years of age. Females are eligible
             to enter and participate in the study if she is (1) non-childbearing potential, (2)
             child bearing potential with negative pregnancy test at screening and Day 1 and agrees
             to use protocol-specified methods of birth control while on study.

          -  HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to
             1000copies/mL

          -  Antiretroviral-naïve (less than or equal to 10 days of prior therapy with any
             antiretroviral agent following a diagnosis of HIV-1 infection)

          -  Signed and dated written informed consent is obtained from the subject or the
             subject's legal representative prior to screening

        Exclusion Criteria:

          -  Women who are pregnant or breastfeeding

          -  Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C
             disease [CDC, 1993], except cutaneous Kaposi's sarcoma not requiring systemic therapy

          -  Subjects with moderate to severe hepatic impairment (Class B or C) as determined by
             Child-Pugh classification

          -  Anticipated need for Hepatitis C virus (HCV) therapy during the study

          -  History or presence of allergy or intolerance to the study drugs or their components
             or drugs of their class

          -  History of malignancy within the past 5 years or ongoing malignancy other than
             cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous
             squamous cell carcinoma; other localized malignancies require agreement between the
             investigator and the Study medical monitor for inclusion of the subject

          -  Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening

          -  Treatment with any of the following agents within 28 days of Screening: radiation
             therapy; cytotoxic chemotherapeutic agents; any immunomodulators

          -  Treatment with any agent, except recognized ART as allowed above, with documented
             activity against HIV-1 in vitro within 28 days of first dose of investigational
             product

          -  Exposure to an experimental drug or experimental vaccine within either 28 days, 5
             half-lives of the test agent, or twice the duration of the biological effect of the
             test agent, whichever is longer, prior to the first dose of investigational product

          -  Any evidence of primary viral resistance based on the presence of any major
             resistance-associated mutation [IAS-USA, 2010] in the Screening result or, if known,
             any historical resistance test result

          -  Any verified Grade 4 laboratory abnormality. Any acute laboratory abnormality at
             Screening, which, in the opinion of the Investigator, would preclude the subject's
             participation in the study of an investigational compound is exclusionary

          -  Alanine aminotransferase (ALT) greater than 5 times the upper limit of normal

          -  ALT greater than 3 times the upper limit of normal and bilirubin greater than or equal
             to 1.5 times the upper limit of normal (with greater than 35% direct bilirubin)

          -  Subject has creatinine clearance of less than 50 mL/min via Cockroft-Gault method

          -  Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal
             bleed, with the exception of anal or rectal bleeding