Phase 3b Open Label Study to Evaluate Switching From Regimens Consisting of a Non-nucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV 1 Infected Patients

• To evaluate the safety and tolerability of the two regimens through Week 96 [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
  To evaluate the safety and tolerability of the two regimens through Week 96
• To evaluate the efficacy of the two regimens through 96 weeks of treatment [ Time Frame: 96 Weeks ] [ Designated as safety issue: No ]
  To evaluate the efficacy of the two regimens through 96 weeks of treatment

The purpose of this study is to evaluate the non-inferiority of Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (EVG/COBI/FTC/TDF) relative to regimens consisting of a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) plus Emtricitabine and Tenofovir DF (FTC/TDF) in maintaining HIV 1 RNA < 50 copies/mL at Week 48 in virologically suppressed, HIV 1 infected subjects.

Randomized, open-label, multicenter, active-controlled study to evaluate switching from regimens consisting of a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) plus FTC/TDF to EVG/COBI/FTC/TDF in virologically suppressed, HIV 1 infected subjects.

• Acquired Immunodeficiency Syndrome
• HIV Infections

• Drug: elvitegravir/cobicistat/emtricitabine/tenofovir df
  Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg single tablet regimen administered orally QD with food.
• Drug: NNRTI plus FTC/TDF

  Current antiretroviral drug regimen consisting of a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) plus FTC/TDF administered orally.

  Efavirenz, nevirapine, and rilpivirine are the only allowed NNRTI agents in combination with FTC/TDF and may include the single tablet regimens, EFV/FTC/TDF or FTC/RPV/TDF.

  Other Names:

  • Truvada®
  • Atripla®

• Experimental: elvitegravir/cobicistat/emtricitabine/tenofovir df
  Switch to the single tablet regimen (STR) consisting of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) for 48 weeks (n = 280)
  Intervention: Drug: elvitegravir/cobicistat/emtricitabine/tenofovir df
• Active Comparator: NNRTI plus FTC/TDF
  Remain on current antiretroviral regimen consisting of a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) plus FTC/TDF for 48 weeks (n = 140) (Efavirenz, nevirapine, and rilpivirine are the only allowed NNRTI agents in combination with FTC/TDF, and may include the STRs: EFV/FTC/TDF or FTC/RPV/TDF).
  Intervention: Drug: NNRTI plus FTC/TDF

Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Be stable on the current formulation(s) of an antiretroviral (ARV) regimen consisting of a NNRTI plus FTC/TDF for ≥ 6 consecutive months preceding the screening visit. This includes subjects that began a regimen with individual drug components and subsequently simplified to include a fixed-dose combination formulation of the same drugs.
• Be on the first of second antiretroviral regimen documented undetectable plasma HIV 1 RNA levels for ≥ 6 months preceding the screening visit
• No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) for any length of time
• Documented historical genotype prior to starting initial antiretroviral therapy showing no known resistance to TDF or FTC
• HIV RNA < 50 copies/mL at the screening visit
• Normal ECG
• Hepatic transaminases ≤ 5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL
• Adequate hematologic function
• Serum amylase ≤ 5 × ULN
• Estimated glomerular filtration rate ≥ 70 mL/min
• Females of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 12 weeks for subjects on EFV/FTC/TDF or efavirenz or 30 days for the rest of subjects 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
• Male subjects must agree to utilize protocol recommended methods of contraception during heterosexual intercourse or be non-heterosexually active, and practice sexual abstinence from the screening visit.
• Age ≥ 18 years

Exclusion Criteria:

• New AIDS-defining condition diagnosed within the 30 days prior to screening
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study
• Experiencing decompensated cirrhosis
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance abuse that would interfere with compliance
• A 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 carcinoma. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and must not be anticipated to require systemic therapy during the study.
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study
• Subjects receiving ongoing therapy with any of the medications, including drugs not to be used with EVG, COBI, FTC, TDF; or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF tablets, or FTC/TDF tablets
• No anticipated need to initiate drugs during the study that are contraindicated
• Receiving other investigational drugs
• Participation in any other clinical trial
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements