A Study to Determine Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) in Human Immunodeficiency Virus (HIV)-1 Infected Antiretroviral Therapy (ART) Naïve Women (ARIA)
Condition: Infection, Human Immunodeficiency Virus; HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Intervention: Dolutegravir/abacavir/lamivudine FDC; Atazanavir; Ritonavir; Tenofovir/emtricitabine FDC
Intervention description: Dolutegravir/abacavir/lamivudine FDC tablets, 50 mg/600 mg/300 mg; Atazanavir capsule 300 mg; Ritonavir tablet 100 mg; Tenofovir/emtricitabine FDC tablet 300 mg/200 mg of FTC
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Tenofovir; Lamivudine; Emtricitabine; Dolutegravir; Abacavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 499.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: antiretroviral therapy naïve; women; once daily; HIV infection; atazanavir; tenofovir/emtricitabine; dolutegravir/abacavir/lamivudine fixed dose combination; integrase inhibitor; ritonavir

Summary:

      This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC
      fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV)
      and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in
      HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety
      and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of
      subjects will be screened in order to ensure a total of approximately 474 subjects will be
      randomized (237 in each study arm)
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected females (gender at birth) >=18 years of age

          -  Women capable of becoming pregnant must use appropriate contraception during the study
             (as defined by the protocol)

          -  HIV-1 infection as documented by Screening plasma HIV-1 RNA >=500 c/mL.

          -  Documentation that the subject is negative for the HLA-B*5701 allele.

          -  Antiretroviral-naïve (<=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

          -  Women who plan to become pregnant during the first 48 weeks of the study

          -  Any subject who has had a medical intervention for gender reassignment

          -  Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C
             disease

          -  Subjects with any degree of hepatic impairment

          -  Subjects positive for hepatitis B at Screening, or anticipated need for HCV therapy
             during the study

          -  History or presence of allergy to the study drugs or their components or drugs of
             their class

          -  Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or
             resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial
             neoplasia

          -  poses a significant suicidality risk

          -  History of osteoporosis with fracture or requiring pharmacologic therapy

          -  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 that alter immune
             responses;

          -  Treatment with any agent, with documented activity against HIV-1 in vitro within 28
             days of first dose of investigational product (IP)

          -  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 IP

          -  Any evidence of primary viral resistance based on the presence of any major
             resistance-associated mutation in the Screening result or, if known, any historical
             resistance test result

          -  Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid
             abnormalities (total cholesterol, triglycerides, High Density Lipoprotein (HDL)
             cholesterol, Low Density Lipoprotein (LDL) cholesterol)

          -  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

          -  Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), or ALT ≥
             3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin)

          -  Subject has CrCL of <50 mL/min via Cockroft-Gault method

          -  Corrected QT interval (QTc (Bazett)) ≥450msec or QTc (Bazett) ≥480msec for subjects
             with bundle branch block.