Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults

• The proportion of subjects with HIV-RNA <20 and <200 copies/mL at Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
  The proportion of subjects with HIV-RNA <20 and <200 copies/mL at Weeks 48 and 96 as defined by FDA snapshot analysis
• The proportion of subjects with HIV-1 RNA <50 copies/mL at Week 96 [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
  The proportion of subjects with HIV-1 RNA <50 copies/mL at Week 96 as defined by FDA snapshot analysis
• Change from Baseline in CD4+ cell count at Weeks 48 and 96 [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
  The change from Baseline in CD4+ cell count at Weeks 48 and 96

• To determine the safety by the percent change from baseline in hip bone mineral density [ Time Frame: 48 Weeks ] [ Designated as safety issue: Yes ]
  To determine the safety of the two treatment regimens as determined by the percent change from baseline in hip bone mineral density at Week 48
• To determine the safety determined by the change from baseline in serum creatinine at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: Yes ]
  To determine the safety of the two treatment regimens as determined by the change from baseline in serum creatinine at Week 48

The purpose of this study is to evaluate the efficacy of a single-tablet regimen (STR)containing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus a STR containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) in HIV-1 positive, antiretroviral treatment naïve adult subjects as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48

Randomized, Double-Blind, multicenter, active-controlled study to evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in achieving HIV-1 RNA < 50 copies/mL at Week 48 as defined by the FDA snapshot analysis in HIV-1 infected subjects

• HIV
• HIV Infections

• Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
  Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir alafenamide 10 mg(E/C/F/TAF) + Placebo to match single tablet regimen of elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (E/C/F/TDF) administered orally QD
• Drug: elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
  Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg (E/C/F/TDF) + placebo to match single tablet regimen of elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) administered orally QD
  Other Name: Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate)

• Experimental: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
  Single tablet regimen of elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir alafenamide 10 mg (E/C/F/TAF) QD+ Placebo to match single-tablet regiment of elvitegravir 150 mg/cobicistat 150 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg (E/C/F/TDF) QD for 96 weeks
  Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
• Active Comparator: elvitegravir/cobicistat/emtricitabine/tenofovir DF
  Single-tablet regimen of elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg (E/C/F/TDF) QD+ Placebo to match single-table regimen of elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) QD for 96 weeks
  Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate

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 ≥ 1,000 copies/mL at screening
• No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PREP), or post-exposure prophylaxis (PEP) up to 6 months prior to screening
• Screening genotype report must show sensitivity to EVG, FTC, TDF
• Normal electrocardiogram (ECG)
• Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
• Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Male subjects and females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
• Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
• Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
• Age ≥ 18 years

Exclusion Criteria:

• A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen (HBsAg) positive
• Hepatitis C antibody positive
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• 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 dosing requirements
• Participation in any other clinical trial (including observational trials) without prior approval
• Subjects receiving ongoing therapy with drugs not to be used with EVG, COBI, FTC, TDF, and TAF or subjects with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF single-tablet regimen tablets