Safety and Efficacy of COBI-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Condition: HIV; HIV Infections
MeSH terms: HIV Infections
Intervention: COBI; RTV; ATV; FTC/TDF; COBI placebo; RTV placebo
Intervention description: Cobicistat (COBI) 150 mg tablet administered orally once daily; Ritonavir (RTV) 100 mg tablet administered orally once daily; Atazanavir (ATV) 300 mg capsule administered orally once daily; Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily; Placebo to match COBI administered orally once daily; Placebo to match RTV administered orally once daily
Intervention MeSH terms: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Atazanavir Sulfate; Cobicistat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 698.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treatment Naive; HIV 1 Infected

Summary:

      The objective of this study is to evaluate the safety and efficacy of a regimen containing
      cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate
      (Truvada®; FTC/TDF) fixed-dose combination (FDC) versus ritonavir-boosted atazanavir
      (ATV+RTV) plus FTC/TDF FDC in HIV-1 infected, antiretroviral treatment-naive adults.

      Participants will be randomized in a 1:1 ratio. Randomization will be stratified by HIV-1 RNA
      level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to understand and sign a written informed consent form, which must be obtained
             prior to initiation of study procedures

          -  Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at screening

          -  No prior use of any approved or investigational antiretroviral drug for any length of
             time

          -  Screening genotype report must show sensitivity to FTC, TDF and ATV

          -  Normal ECG

          -  Adequate renal function (eGFR calculated using the Cockcroft-Gault equation ≥ 70
             mL/min)

          -  Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

          -  Adequate hematologic function

          -  Serum amylase ≤ 5 x ULN

          -  Males and females of childbearing potential must agree to utilize highly effective
             contraception methods from screening throughout the duration of study treatment and
             for 30 days following the last dose of study drug.

          -  Age ≥ 18 years

          -  Life expectancy ≥ 1 year

        Exclusion Criteria:

          -  A new AIDS-defining condition diagnosed within the 30 days prior to screening

          -  Receiving drug treatment for Hepatitis C, or anticipated to receive treatment for
             Hepatitis C

          -  Subjects experiencing decompensated cirrhosis

          -  Females who are breastfeeding

          -  Positive serum pregnancy test (female of childbearing potential)

          -  Have an implanted defibrillator or pacemaker

          -  Have an ECG PR interval ≥ 220 msec

          -  Current alcohol or substance use judged by the Investigator to potentially interfere
             with subject study compliance.

          -  A history of malignancy within the past 5 years or ongoing malignancy other than
             cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive
             cutaneous squamous carcinoma.

          -  Active, serious infections (other than HIV-1 infection) requiring parenteral
             antibiotic or antifungal therapy within 30 days prior to baseline.

          -  Medications contraindicated for use with COBI, emtricitabine (FTC), tenofovir
             disoproxil fumarate (TDF), atazanavir (ATV), ritonavir (RTV) or subjects with any
             known allergies to the excipients of COBI tablets, Truvada tablets, atazanavir
             capsules or ritonavir tablets.

          -  Participation in any other clinical trial without prior approval from the sponsor is
             prohibited while participating in this trial.

          -  Any other clinical condition or prior therapy that, in the opinion of the
             Investigator, would make the subject unsuitable for the study or unable to comply with
             the dosing requirements.