Clinical research study involving an experimental combination medication called EVG/COBI/FTC/TDF. This is 1 pill containing 2 experimental medications, EVG and COBI, plus 2 medications already approved for the treatment of HIV-1 infection, FTC and TDF. In this study neither the patient or the investigator will know whether the patient is receiving EVG/COBI/FTC/TDF or the comparator drug ritonavir-boosted atazanavir with FTC/TDF. This is a randomized (by chance, like a flip of a coin) study.

Phase 1

Conditions: Human Immunodeficiency Virus (HIV-1) Infections
MedDRA version: 20.0Level: LLTClassification code 10020192Term: HIV-1System Organ Class: 100000004862
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2012-003708-11-BE

Lead Sponsor: Gilead Sciences Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 510

Inclusion Criteria

For the blinded phase:
1. Female (at birth), age = 18 years
2. Plasma HIV-1 RNA levels = 500 copies/mL at screening
3. Adequate renal function: Estimated glomerular filtration rate = 70 mL/min according to the Cockcroft-Gault formula
4. No prior use of any approved or experimental antiretroviral drug for any length of time
5. Screening genotype report shows sensitivity to FTC, TDF and ATV
6. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
7. Hepatic transaminases (AST and ALT) = 5 × upper limit of normal (ULN)
8. Total bilirubin = 1.5 mg/dL or normal bilirubin
9. Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets = 50,000/mm3; hemoglobin = 8.5 g/dL)
10. Serum amylase = 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is = 5 × ULN)
11. Women of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug. Women who utilize hormonal contraceptives as one of their birth control methods must have used the same method for at least three months prior to study dosing.

For the Open-Label Extension
1. Completed 48 weeks of the blinded phase of the study
2. Plasma HIV-1 RNA level <50 copies/mL at Week 48 or upon retest within protocol-specified window
3. Adequate renal function, estimated glomerular filtration rate = 50 mL/min according to the Cockcroft Gault formula
4. Hepatic transaminases (AST and ALT) = 5 x upper limit of normal (ULN)
5. Total bilirubin = 1.5 mg/dL or normal direct bilirubin
6. Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets = 50,000/mm3; hemoglobin = 8.5 g/dL)
7. Serum amylase = 5 x ULN (subjects with serum amylase > 5 x ULN will remain eligible if serum lipase is = 5 x ULN)
8. Women of childbearing potential
a. Must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug. Women who utilize hormonal contraceptives as one of their birth control methods must have used the same method for at least three months prior to study dosing.
b. Must not be breastfeeding
c. Must have negative pregnancy test
9. Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 484
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion Criteria

• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study
• Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Subjects 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 (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), 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 (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline.
• 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.
• Subjects receiving ongoing therapy with any of the medications contraindicated in the protocol,
including drugs not to be used with EVG, COBI, FTC, TDF, ATV, RTV; or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF STR, Truvada tablets, atazanavir capsules or
ritonavir tablets.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil<br>fumarate versus ritonavir-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate in HIV-1 infected, antiretroviral treatment-naïve adult women as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48;Secondary Objective: To evaluate the safety and tolerability of the two treatment regimens<br>To evaluate the change from baseline in CD4+ cell count;Primary end point(s): The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 of the double-blind phase as defined by the FDA snapshot analysis.;Timepoint(s) of evaluation of this end point: Week 48

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • The change from baseline in CD4+ cell count at Week 48 of the doubleblind phase.<br>• The proportion of subjects receiving open-label EVG/COBI/FTC/TDF with HIV-1 RNA < 50 copies/mL (by FDA snapshot) at Week 48 of the open-label extension (OLE).<br>• The proportion of subjects receiving EVG/COBI/FTC/TAF or ATV/r plus TVD with HIV-RNA <50 copies/mL (By FDA snapshot) at Week 48 of the OLE.<br>• The change in CD4+ cell count at Week 48 of the OLE.;Timepoint(s) of evaluation of this end point: Week 48

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