Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01363011
• Collaborator: (none)
• Enrollment: 106
• Locations: 51
• Arms: 2
• Duration (Months): 45.1
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is to characterize the effect of cobicistat-based regimens on parameters of renal function in participants with HIV infection and who have mild to moderate renal impairment, and to assess the safety and tolerability of the regimens in order to generate appropriate dosing recommendations.

Condition or Disease	Intervention/Treatment	Phase
Acquired Immunodeficiency Syndrome; HIV Infections	Drug: E/C/F/TDF; Drug: COBI; Drug: ATV; Drug: DRV; Drug: NRTI	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Open-label Safety Study of Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E/C/F/TDF (Cohort 1) Participants who have not received prior antiretroviral (ARV) treatment and who are virologically unsuppressed at baseline will initiate treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) single-tablet regimen (STR) for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.	Drug: E/C/F/TDF; E/C/F/TDF (150/150/200/300 mg) STR administered orally once daily; Other Names: Stribild®
Experimental: COBI+PI+2 NRTI (Cohort 2) Participants who have received prior ARV treatment and who are virologically suppressed at baseline will continue their treatment regimen, switching the regimen's pharmacoenhancer component from ritonavir to cobicistat (COBI), and continuing their existing protease inhibitor (PI; either atazanavir (ATV) or darunavir (DRV)) plus 2 nucleoside reverse transcriptase inhibitor (NRTI) regimen for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.	Drug: COBI; COBI 150 mg tablet administered with food orally once daily; Other Names: Tybost® ; Drug: ATV; ATV 300 mg tablet administered orally once daily; Other Names: Reyataz® ; Drug: DRV; DRV 800 mg tablet administered orally once daily; Other Names: Prezista® ; Drug: NRTI; Participants will receive 2 investigator-selected NRTIs, which may include abacavir (ABC), lamivudine (3TC)/zidovudine (ZDV), didanosine (DDI), emtricitabine (FTC), ABC/3TC, 3TC, tenofovir disoproxil fumarate (TDF), or FTC/TDF, administered according to prescribing information.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1) [Baseline; Week 24]

   Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 1 (treatment-naive).

2. Change From Baseline in eGFR-CG at Week 24 (Cohort 2) [Baseline; Week 24]

   Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 2 (treatment-experienced).

3. Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1) [Baseline; Week 24]

   Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.

4. Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2) [Baseline; Week 24]

   Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.

5. Change From Baseline in eGFR Using the Chronic Kidney Disease, Epidemiology Collaboration (CKD-EPI) Formula Based on Cystatin C Equation at Week 24 (Cohort 1) [Baseline; Week 24]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.

6. Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2) [Baseline; Week 24]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.

7. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1) [Baseline; Week 24]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.

8. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2) [Baseline; Week 24]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.

9. Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1) [Baseline; Weeks 2, 4, and 24]

   Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 1 (treatment-naive). aGFR was calculated using iohexol plasma clearance.

10. Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2) [Baseline; Weeks 2, 4, and 24]

    Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 2 (treatment-experienced). aGFR was calculated using iohexol plasma clearance.

11. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1) [Week 24]

    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.

12. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2) [Week 24]

    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.

Secondary Outcome Measures

1. Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

2. Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2) [Baseline; Week 48]

   Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

3. Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

4. Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

5. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

6. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

7. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

8. Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2) [Baseline; Weeks 48 and 96]

   Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.

9. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1) [Weeks 48 and 96]

   The percentage of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.

10. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2) [Weeks 48 and 96]

    The percentage of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.

11. Percentage of Participants Who Experienced Adverse Events (Cohort 1) [Up to 147 weeks plus 30 days]

    Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 1 (treatment-naive). A participant was counted once if they had a qualifying event.

12. Percentage of Participants Who Experienced Adverse Events (Cohort 2) [Up to 166 weeks plus 30 days]

    Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 2 (treatment-experienced). A participant was counted once if they had a qualifying event.

13. Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1) [Up to 147 weeks plus 30 days]

    Laboratory abnormalities were summarized for Cohort 1 (treatment-naive) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.

14. Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2) [Up to 166 weeks plus 30 days]

    Laboratory abnormalities were summarized for Cohort 2 (treatment-experienced) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.

15. Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    AUCtau was analyzed for Cohort 1 (treatment-naive) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

16. Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    AUCtau was analyzed for Cohort 2 (treatment-experienced) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

17. Plasma Pharmacokinetics of COBI: Cmax (Cohort 1) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    Cmax was analyzed for Cohort 1 (treatment-naive) and was defined as the maximum observed concentration of drug in plasma.

18. Plasma Pharmacokinetics of COBI: Cmax (Cohort 2) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    Cmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the maximum observed concentration of drug in plasma.

19. Plasma Pharmacokinetics of COBI: Ctau (Cohort 1) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    Ctau was analyzed for Cohort 1 (treatment-naive) and was defined as the observed drug concentration at the end of the dosing interval.

20. Plasma Pharmacokinetics of COBI: Ctau (Cohort 2) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    Ctau was analyzed for Cohort 2 (treatment-experienced) and was defined as the observed drug concentration at the end of the dosing interval.

21. Plasma Pharmacokinetics of COBI: Tmax (Cohort 1) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.

22. Plasma Pharmacokinetics of COBI: Tmax (Cohort 2) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.

23. Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    t1/2 was analyzed for Cohort 1 (treatment-naive) and was defined as the estimate of the terminal elimination half-life of the drug.

24. Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2) [Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.]

    t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Cohort 1 (treatment-naive)

• Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening

• Screening genotype report must show sensitivity to FTC and TDF

• No prior use of any approved or investigational antiretroviral drug for any length of time

Cohort 2 (treatment-experienced, pharmacoenhancer switch)

• Subjects must be receiving ATV 300 mg/ritonavir (RTV) 100 mg plus 2 NRTIs OR DRV 800 mg/RTV 100 mg plus 2 NRTIs for at least 6 months prior to screening

• Plasma HIV-1 RNA concentrations at undetectable levels in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening

• Subjects experiencing intolerance to RTV (as determined by the investigator)

Both groups

• The ability to understand and sign a written informed consent form

• Normal ECG

• Mild to moderate renal function

• Stable renal function

• Hepatic transaminases (AST and ALT) ≤ 5 x the upper limit of the normal range (ULN)

• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert's Syndrome or hyperbilirubinemia due to atazanavir therapy may have total bilirubin up to 5 x ULN)

• 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

Exclusion Criteria:

• 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)

• 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

• Receiving ongoing therapy with any of medications contraindicated for use with elvitegravir (EVG), COBI, FTC, TDF, ATV, DRV; or subjects with any known allergies to the excipients of E/C/F/TDF STR, COBI tablets, ATV capsules or DRV tablets or contraindicated for the 2 NRTIs as part of the PI/co regimen

• Participation in any other clinical trial without prior approval

• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spectrum Medical Group	Phoenix	Arizona	United States	85012
2	Health for Life Clinic	Little Rock	Arkansas	United States	72207
3	AHF Research Center	Beverly Hills	California	United States	90211
4	Kaiser Permanente	Los Angeles	California	United States	90027
5	Peter J. Ruane, M.D., Inc.	Los Angeles	California	United States	90036
6	Anthony Mills, MD, Inc.	Los Angeles	California	United States	90069
7	Orange Coast Medical Group	Newport Beach	California	United States	92663
8	East Bay AIDS Center	Oakland	California	United States	94609
9	University of California, Davis	Sacramento	California	United States	01105
10	Metropolis Medical	San Francisco	California	United States	94115
11	National Jewish Health	Denver	Colorado	United States	80206
12	Yale University School of Medicine AIDS Program	New Haven	Connecticut	United States	06520
13	Whitman Walker Clinic	Washington	District of Columbia	United States	20009
14	Medical Faculty Associates	Washington	District of Columbia	United States	20037
15	Therafirst Medical Center	Fort Lauderdale	Florida	United States	33308
16	Broward Health	Fort Lauderdale	Florida	United States	33311
17	Gary J. Richmond.M.D.,P.A.	Fort Lauderdale	Florida	United States	33316
18	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982
19	Orlando Immunology Center	Orlando	Florida	United States	32803
20	IDOCF/ValueHealthMD, LLC	Orlando	Florida	United States	32806
21	Infectious Disease Specialists of Atlanta	Decatur	Georgia	United States	30033
22	Mercer University/ Mercer Medicine Clinical Research	Macon	Georgia	United States	31201
23	Northstar Medical Center	Chicago	Illinois	United States	60657
24	The Research Institute	Springfield	Massachusetts	United States	01105
25	Central West Clinical Research, Inc.	St.Louis	Missouri	United States	63108
26	ID Care	Hillsborough	New Jersey	United States	08844
27	North Shore University Hospital	Manhasset	New York	United States	11030
28	Chelsea Village Medical	New York	New York	United States	10011
29	Mount Sinai Downtown Comprehensive Health Program	New York	New York	United States	10011
30	AIDS Care	Rochester	New York	United States	14607
31	Carolinas Medical Center	Charlotte	North Carolina	United States	28207
32	Southwest Infectious Disease Clinical Research, Inc.	Addison	Texas	United States	75001
33	Tarrant County Infectious Disease Associates	Fort Worth	Texas	United States	76104
34	Therapeutic Concepts, PA	Houston	Texas	United States	77004
35	Taylor Square Private Clinic	Darlinghurst		Australia	2010
36	Infectious Diseases Unit - The Alfred Hospital	Melbourne		Australia	3004
37	Holdsworth House Medical Practice	Sydney		Australia	2010
38	Landeskrankenhaus Graz West	Graz		Austria	8020
39	Otto Wagner Spital	Wien		Austria	1140
40	Sunnybrook Health Sciences Center	Toronto	Ontario	Canada	M4N3M5
41	Clinique Medicale du Quartier Latin	Montreal		Canada	H2L5B1
42	Instituto Dominicano de Estudio Virologicos	Santo Domingo		Dominican Republic	99999
43	Center for HIV and Hepatogastroenterology	Düsseldorf		Germany	40237
44	Hospital Civil de Guadalajara "Fray Antonio Alcalde"	Guadalajara		Mexico	44280
45	Clinical Research Puerto Rico	San Juan		Puerto Rico	00909
46	HOPE Clinical Research	San Juan		Puerto Rico	00909
47	Brighton and Sussex University Hospitals NHS Trust	Brighton		United Kingdom	BN2 1ES
48	Barts & the London NHS Trust	London		United Kingdom	E1 1BB
49	Homerton University Hospital	London		United Kingdom	SE5 0DJ
50	Guy's King's and St. Thomas' School of Medicine	London		United Kingdom	SE5 9RJ
51	St Stephen's AIDS Trust	London		United Kingdom	SW10 9NH

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Javier Szwarcberg, MD, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01363011
• Other Study ID Numbers: GS-US-236-0118
• First Posted: Jun 1, 2011
• Last Update Posted: May 2, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Gilead Sciences: HIV-1; Treatment Naive; Treatment Experienced
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Darunavir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 40 study sites in Australia, Europe, and North America. The first participant was screened on 13 May 2011. The last study visit occurred on 16 February 2015.
Pre-assignment Detail	177 participants were screened.

Arm/Group Title	E/C/F/TDF (Cohort 1)	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had not received prior antiretroviral (ARV) treatment and who were virologically unsuppressed at baseline initiated treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) (150/150/200/300 mg) single-tablet regimen (STR) once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to cobicistat (Tybost®; COBI) 150 mg, while continuing the other components of their ARV regimen (atazanavir (ATV) 300 mg or darunavir (DRV) 800 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTI)) for up to 96 weeks. These 2 NRTIs may have included abacavir (ABC), lamivudine (3TC)/zidovudine (ZDV), didanosine (DDI), emtricitabine (FTC), ABC/3TC, 3TC, tenofovir disoproxil fumarate (TDF), or emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF), administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Period Title: Main Study
STARTED	33	73
COMPLETED	29	64
NOT COMPLETED	4	9
Period Title: Main Study
STARTED	18	49
COMPLETED	13	41
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	E/C/F/TDF (Cohort 1)	COBI+PI+2 NRTIs (Cohort 2)	Total
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.	Total of all reporting groups
Overall Participants	33	73	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (12.1)	54 (9.5)	53 (10.5)
Sex: Female, Male (Count of Participants)
Female	6 18.2%	13 17.8%	19 17.9%
Male	27 81.8%	60 82.2%	87 82.1%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	1 3%	0 0%	1 0.9%
Asian	0 0%	1 1.4%	1 0.9%
Black or African Heritage	13 39.4%	14 19.2%	27 25.5%
White	14 42.4%	56 76.7%	70 66%
Other	5 15.2%	2 2.7%	7 6.6%
Race/Ethnicity, Customized (participants) [Number]
Hispanic/Latino	9 27.3%	19 26%	28 26.4%
Non-Hispanic/Latino	24 72.7%	54 74%	78 73.6%
Region of Enrollment (participants) [Number]
United States	19 57.6%	33 45.2%	52 49.1%
Mexico	0 0%	9 12.3%	9 8.5%
Canada	4 12.1%	2 2.7%	6 5.7%
Dominican Republic	5 15.2%	1 1.4%	6 5.7%
Austria	0 0%	2 2.7%	2 1.9%
Australia	1 3%	5 6.8%	6 5.7%
Germany	0 0%	3 4.1%	3 2.8%
United Kingdom	4 12.1%	18 24.7%	22 20.8%
HIV Disease Status (participants) [Number]
Asymptomatic	28 84.8%	37 50.7%	65 61.3%
Symptomatic HIV Infection	3 9.1%	18 24.7%	21 19.8%
AIDS	2 6.1%	18 24.7%	20 18.9%
Hepatitis B Virus (HBV) Surface Antigen Status (participants) [Number]
Positive	1 3%	4 5.5%	5 4.7%
Negative	32 97%	69 94.5%	101 95.3%
Hepatitis C Virus (HCV) Antibody Status (participants) [Number]
Positive	2 6.1%	10 13.7%	12 11.3%
Negative	30 90.9%	63 86.3%	93 87.7%
Indeterminate	1 3%	0 0%	1 0.9%
HIV-1 RNA Category (participants) [Number]
< 50 copies/mL	0 0%	73 100%	73 68.9%
≥ 50 to < 1,000 copies/mL	0 0%	0 0%	0 0%
≥ 1,000 to ≤ 100,000 copies/mL	24 72.7%	0 0%	24 22.6%
> 100,000 copies/mL	9 27.3%	0 0%	9 8.5%
CD4 Cell Count (participants) [Number]
≤ 50 cells/µL	1 3%	0 0%	1 0.9%
51 to ≤ 200 cells/µL	3 9.1%	3 4.1%	6 5.7%
201 to ≤ 350 cells/µL	13 39.4%	5 6.8%	18 17%
351 to ≤ 500 cells/µL	10 30.3%	16 21.9%	26 24.5%
> 500 cells/µL	6 18.2%	49 67.1%	55 51.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1)
Description	Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 1 (treatment-naive).
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (treatment-naive only): participants in the treatment-naive group who were randomized and received at least one dose of study drug

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Baseline (n = 33)	72.9
Change at Week 24 (n = 30)	-5.2

2. Primary Outcome

Title	Change From Baseline in eGFR-CG at Week 24 (Cohort 2)
Description	Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 2 (treatment-experienced).
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (treatment-experienced only): participants in the treatment-experienced group who were randomized and received at least one dose of study drug

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Baseline (n = 73)	71.4
Change at Week 24 (n = 67)	-3.7

3. Secondary Outcome

Title	Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)
Description	Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Change at Week 48 (n = 28)	-7.6
Change at Week 96 (n = 25)	-7.9

4. Secondary Outcome

Title	Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)
Description	Change from baseline in eGFR-CG at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set (treatment-experienced only) with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Change at Week 48 (n = 63)	-3.8
Change at Week 96 (n = 50)	-5.0

5. Secondary Outcome

Title	Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)
Description	Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Change at Week 48 (n = 28)	-12.1
Change at Week 96 (n = 25)	-12.9

6. Secondary Outcome

Title	Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)
Description	Change from baseline in eGFR-MDRD at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Change at Week 48 (n = 63)	-3.9
Change at Week 96 (n = 50)	-2.8

7. Secondary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Change at Week 48 (n = 28)	1.9
Change at Week 96 (n = 25)	12.4

8. Secondary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Change at Week 48 (n = 63)	-4.7
Change at Week 96 (n = 50)	-2.4

9. Primary Outcome

Title	Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1)
Description	Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Baseline (n = 33)	77.1
Change at Week 24 (n = 30)	-7.4

10. Primary Outcome

Title	Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)
Description	Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Baseline (n = 73)	65.8
Change at Week 24 (n = 67)	-3.4

11. Primary Outcome

Title	Change From Baseline in eGFR Using the Chronic Kidney Disease, Epidemiology Collaboration (CKD-EPI) Formula Based on Cystatin C Equation at Week 24 (Cohort 1)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Baseline (n = 33)	77.6
Change at Week 24 (n = 30)	0.3

12. Primary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Baseline (n = 73)	78.6
Change at Week 24 (n = 67)	-2.7

13. Secondary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Change at Week 48 (n = 28)	1.6
Change at Week 96 (n = 25)	12.6

14. Secondary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area. This outcome is to measure the long-term effect of COBI-containing regimens on renal parameters.
Time Frame	Baseline; Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Change at Week 48 (n = 63)	-4.7
Change at Week 96 (n = 50)	-2.8

15. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1)
Description	The percentage of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
Time Frame	Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Full Analysis Set with available data was analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Week 48 (n = 33)	78.8 238.8%
Week 96 (n = 27)	88.9 269.4%

16. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2)
Description	The percentage of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 were analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
Time Frame	Weeks 48 and 96

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Week 48 (n = 73)	82.2 249.1%
Week 96 (n = 54)	90.7 274.8%

17. Secondary Outcome

Title	Percentage of Participants Who Experienced Adverse Events (Cohort 1)
Description	Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 1 (treatment-naive). A participant was counted once if they had a qualifying event.
Time Frame	Up to 147 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Any AE	100.0 303%
Drug-related AE	48.5 147%
Grade 3 or higher AE	21.2 64.2%
AE leading to drug discontinuation	12.1 36.7%
Serious AE	18.2 55.2%
AE of proximal renal tubulopathy	0 0%

18. Primary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Treatment-naive participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Baseline (n = 33)	76.9
Change at Week 24 (n = 30)	0.3

19. Primary Outcome

Title	Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2)
Description	Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m^2 body surface area.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Baseline (n = 73)	78.2
Change at Week 24 (n = 67)	-2.8

20. Primary Outcome

Title	Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)
Description	Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 1 (treatment-naive). aGFR was calculated using iohexol plasma clearance.
Time Frame	Baseline; Weeks 2, 4, and 24

Outcome Measure Data

Analysis Population Description

Pharmacokinetic/Pharmacodynamic (PK/PD) Substudy Analysis Set (treatment-naive only): participants in the treatment-naive group who were enrolled and received at least one dose of study drug and who had data for steady-state PK parameters at the relevant time points were analyzed.

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	1
Baseline	81.6
Change at Week 2	-12.1
Change at Week 4	-7.3
Change at Week 24	-3.3

21. Primary Outcome

Title	Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)
Description	Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 2 (treatment-experienced). aGFR was calculated using iohexol plasma clearance.
Time Frame	Baseline; Weeks 2, 4, and 24

Outcome Measure Data

Analysis Population Description

PK/PD Substudy Analysis Set (treatment-experienced only): participants in the treatment-experienced group who were enrolled and received at least one dose of study drug and who had data for steady-state PK parameters at the relevant time points were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	14
Baseline	82.5
Change at Week 2 (n=13)	1.6
Change at Week 4 (n=13)	7.0
Change at Week 24 (n=11)	-4.1

22. Primary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)
Description	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (treatment-naive only): participants in the treatment-naive group who were randomized and received at least one dose of study drug

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Number [percentage of participants]	84.8 257%

23. Primary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)
Description	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (treatment-experienced only): participants in the treatment-experienced group who were randomized and received at least one dose of study drug

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Number [percentage of participants]	90.4 273.9%

24. Secondary Outcome

Title	Percentage of Participants Who Experienced Adverse Events (Cohort 2)
Description	Adverse events (AEs) occurring from baseline up to 30 days following the last dose of study drug were summarized for Cohort 2 (treatment-experienced). A participant was counted once if they had a qualifying event.
Time Frame	Up to 166 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (treatment-experienced only)

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	73
Any AE	93.2 282.4%
Drug-related AE	27.4 83%
Grade 3 or higher AE	28.8 87.3%
AE leading to drug discontinuation	11.0 33.3%
Serious AE	15.1 45.8%
AE of proximal renal tubulopathy	0 0%

25. Secondary Outcome

Title	Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)
Description	Laboratory abnormalities were summarized for Cohort 1 (treatment-naive) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.
Time Frame	Up to 147 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	33
Any laboratory abnormality	100.0 303%
Grade 3 or 4 laboratory abnormality	39.4 119.4%

26. Secondary Outcome

Title	Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)
Description	Laboratory abnormalities were summarized for Cohort 2 (treatment-experienced) and were defined as values that increased at least one toxicity grade from baseline at any time postbaseline up to and including the date of last dose of study drug plus 30 days. A participant was counted once if they had a qualifying event.
Time Frame	Up to 166 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

Treatment-experienced participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	72
Any laboratory abnormality	100.00 303%
Grade 3 or 4 laboratory abnormality	50.0 151.5%

27. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)
Description	AUCtau was analyzed for Cohort 1 (treatment-naive) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

PK/PD Substudy Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	1
Week 2	16554.7
Week 4	12704.1
Week 24	9799.7

28. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: AUCtau (Cohort 2)
Description	AUCtau was analyzed for Cohort 2 (treatment-experienced) and was defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	14
Week 2 (n = 13)	12458.0 (6179.06)
Week 4 (n = 13)	11165.3 (4185.86)
Week 24 (n = 11)	13980.5 (8029.03)

29. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: Cmax (Cohort 1)
Description	Cmax was analyzed for Cohort 1 (treatment-naive) and was defined as the maximum observed concentration of drug in plasma.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

PK/PD Substudy Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	1
Week 2	1734.6
Week 4	1522.9
Week 24	1266.4

30. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: Cmax (Cohort 2)
Description	Cmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the maximum observed concentration of drug in plasma.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	14
Week 2 (n = 13)	1366.7 (508.32)
Week 4 (n = 13)	1297.7 (424.06)
Week 24 (n = 11)	1568.6 (618.84)

31. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: Ctau (Cohort 1)
Description	Ctau was analyzed for Cohort 1 (treatment-naive) and was defined as the observed drug concentration at the end of the dosing interval.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

PK/PD Substudy Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	1
Week 2	150.5
Week 4	37.3
Week 24	24.2

32. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: Ctau (Cohort 2)
Description	Ctau was analyzed for Cohort 2 (treatment-experienced) and was defined as the observed drug concentration at the end of the dosing interval.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	14
Week 2 (n = 13)	79.9 (79.01)
Week 4 (n = 13)	71.3 (61.27)
Week 24 (n = 11)	139.8 (238.84)

33. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: Tmax (Cohort 1)
Description	Tmax was analyzed for Cohort 1 (treatment-naive) and was defined as the time of Cmax.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

PK/PD Substudy Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	1
Week 2	4.00
Week 4	2.00
Week 24	4.00

34. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: Tmax (Cohort 2)
Description	Tmax was analyzed for Cohort 2 (treatment-experienced) and was defined as the time of Cmax.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	14
Week 2 (n = 13)	3.92
Week 4 (n = 13)	4.92
Week 24 (n = 11)	3.00

35. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: t1/2 (Cohort 1)
Description	t1/2 was analyzed for Cohort 1 (treatment-naive) and was defined as the estimate of the terminal elimination half-life of the drug.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

PK/PD Substudy Analysis Set (treatment-naive only)

Arm/Group Title	E/C/F/TDF (Cohort 1)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.
Measure Participants	1
Week 2	6.14
Week 4	3.57
Week 24	3.63

36. Secondary Outcome

Title	Plasma Pharmacokinetics of COBI: t1/2 (Cohort 2)
Description	t1/2 was analyzed for Cohort 2 (treatment-experienced) and was defined as the estimate of the terminal elimination half-life of the drug.
Time Frame	Blood samples were collected at 0 (predose), 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 8.0, 12.0, and 24.0 hours postdose at baseline and Weeks 2, 4, and 24.

Outcome Measure Data

Analysis Population Description

Participants in the PK/PD Substudy Analysis Set (treatment-experienced only) with available postbaseline data were analyzed.

Arm/Group Title	COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTIs) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
Measure Participants	14
Week 2 (n = 13)	4.37
Week 4 (n = 12)	3.98
Week 24 (n = 10)	3.77

Adverse Events

Time Frame	Baseline through end of study drug treatment (average: Cohort 1 = 93.7 weeks; Cohort 2 = 101.2 weeks) plus 30 days
Adverse Event Reporting Description	Safety Analysis Set: participants were randomized and received at least one dose of study drug
Arm/Group Title	E/C/F/TDF (Cohort 1)		COBI+PI+2 NRTIs (Cohort 2)
Arm/Group Description	Main Study: Participants who had not received prior ARV treatment and who were virologically unsuppressed at baseline initiated treatment with E/C/F/TDF (150/150/200/300 mg) STR once daily for up to 96 weeks. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.		Main Study: Participants who had received prior ARV treatment and who were virologically suppressed at baseline switched their regimen's pharmacoenhancer component from ritonavir to COBI 150 mg, while continuing the other components of their ARV regimen (ATV 300 mg or DRV 800 mg plus 2 NRTI) for up to 96 weeks. These 2 NRTIs may have included ABC, 3TC/ZDV, DDI, FTC, ABC/3TC, 3TC, TDF, or FTC/TDF, administered according to prescribing information. Extension Phase: Participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.
All Cause Mortality
	E/C/F/TDF (Cohort 1)		COBI+PI+2 NRTIs (Cohort 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	E/C/F/TDF (Cohort 1)		COBI+PI+2 NRTIs (Cohort 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/33 (18.2%)		11/73 (15.1%)
Blood and lymphatic system disorders
Anaemia	1/33 (3%)		0/73 (0%)
Cardiac disorders
Acute coronary syndrome	0/33 (0%)		1/73 (1.4%)
Acute myocardial infarction	0/33 (0%)		1/73 (1.4%)
Angina pectoris	0/33 (0%)		1/73 (1.4%)
Coronary artery stenosis	0/33 (0%)		1/73 (1.4%)
Right ventricular failure	1/33 (3%)		0/73 (0%)
Gastrointestinal disorders
Gastrointestinal fistula	0/33 (0%)		1/73 (1.4%)
Nausea	0/33 (0%)		1/73 (1.4%)
Peptic ulcer	0/33 (0%)		1/73 (1.4%)
General disorders
Chest pain	0/33 (0%)		1/73 (1.4%)
Hepatobiliary disorders
Cholecystitis chronic	0/33 (0%)		1/73 (1.4%)
Infections and infestations
Cellulitis	0/33 (0%)		1/73 (1.4%)
Hepatitis C	1/33 (3%)		0/73 (0%)
Infected cyst	1/33 (3%)		0/73 (0%)
Pelvic inflammatory disease	0/33 (0%)		1/73 (1.4%)
Sepsis	0/33 (0%)		1/73 (1.4%)
Injury, poisoning and procedural complications
Skull fracture	0/33 (0%)		1/73 (1.4%)
Investigations
Blood creatine phosphokinase increased	1/33 (3%)		0/73 (0%)
Transaminases increased	0/33 (0%)		1/73 (1.4%)
Metabolism and nutrition disorders
Diabetes mellitus	1/33 (3%)		0/73 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease	1/33 (3%)		0/73 (0%)
Lymphoma	1/33 (3%)		0/73 (0%)
Nervous system disorders
Cerebral ischaemia	0/33 (0%)		1/73 (1.4%)
Convulsion	0/33 (0%)		1/73 (1.4%)
Hemiparesis	0/33 (0%)		1/73 (1.4%)
Psychiatric disorders
Suicidal ideation	0/33 (0%)		1/73 (1.4%)
Renal and urinary disorders
Nephrolithiasis	0/33 (0%)		1/73 (1.4%)
Skin and subcutaneous tissue disorders
Angioedema	1/33 (3%)		1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	E/C/F/TDF (Cohort 1)		COBI+PI+2 NRTIs (Cohort 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/33 (93.9%)		66/73 (90.4%)
Blood and lymphatic system disorders
Anaemia	3/33 (9.1%)		1/73 (1.4%)
Lymphadenopathy	2/33 (6.1%)		2/73 (2.7%)
Neutropenia	2/33 (6.1%)		0/73 (0%)
Eye disorders
Vision blurred	3/33 (9.1%)		1/73 (1.4%)
Gastrointestinal disorders
Abdominal pain	3/33 (9.1%)		1/73 (1.4%)
Abdominal pain upper	2/33 (6.1%)		4/73 (5.5%)
Constipation	3/33 (9.1%)		5/73 (6.8%)
Diarrhoea	12/33 (36.4%)		10/73 (13.7%)
Dyspepsia	3/33 (9.1%)		3/73 (4.1%)
Nausea	6/33 (18.2%)		9/73 (12.3%)
Proctalgia	2/33 (6.1%)		0/73 (0%)
Vomiting	5/33 (15.2%)		4/73 (5.5%)
General disorders
Fatigue	3/33 (9.1%)		5/73 (6.8%)
Oedema peripheral	3/33 (9.1%)		5/73 (6.8%)
Pain	2/33 (6.1%)		2/73 (2.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/33 (0%)		8/73 (11%)
Infections and infestations
Acute sinusitis	1/33 (3%)		4/73 (5.5%)
Bronchitis	3/33 (9.1%)		10/73 (13.7%)
Chikungunya virus infection	2/33 (6.1%)		1/73 (1.4%)
Conjunctivitis	0/33 (0%)		4/73 (5.5%)
Folliculitis	2/33 (6.1%)		5/73 (6.8%)
Gastroenteritis	2/33 (6.1%)		2/73 (2.7%)
Herpes simplex	2/33 (6.1%)		1/73 (1.4%)
Influenza	4/33 (12.1%)		8/73 (11%)
Lower respiratory tract infection	1/33 (3%)		5/73 (6.8%)
Nasopharyngitis	6/33 (18.2%)		14/73 (19.2%)
Oral candidiasis	3/33 (9.1%)		1/73 (1.4%)
Pyuria	3/33 (9.1%)		1/73 (1.4%)
Rhinitis	2/33 (6.1%)		4/73 (5.5%)
Sinusitis	4/33 (12.1%)		7/73 (9.6%)
Syphilis	4/33 (12.1%)		1/73 (1.4%)
Tinea cruris	2/33 (6.1%)		0/73 (0%)
Tinea pedis	2/33 (6.1%)		1/73 (1.4%)
Upper respiratory tract infection	1/33 (3%)		15/73 (20.5%)
Urethritis	2/33 (6.1%)		1/73 (1.4%)
Urinary tract infection	5/33 (15.2%)		3/73 (4.1%)
Investigations
Blood alkaline phosphatase increased	2/33 (6.1%)		0/73 (0%)
Blood creatine phosphokinase increased	2/33 (6.1%)		2/73 (2.7%)
Glomerular filtration rate decreased	2/33 (6.1%)		2/73 (2.7%)
Metabolism and nutrition disorders
Decreased appetite	3/33 (9.1%)		5/73 (6.8%)
Dehydration	2/33 (6.1%)		0/73 (0%)
Gout	2/33 (6.1%)		2/73 (2.7%)
Hypercholesterolaemia	2/33 (6.1%)		1/73 (1.4%)
Hyperglycaemia	2/33 (6.1%)		2/73 (2.7%)
Hyperlipidaemia	2/33 (6.1%)		0/73 (0%)
Hypertriglyceridaemia	0/33 (0%)		4/73 (5.5%)
Hypokalaemia	1/33 (3%)		4/73 (5.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/33 (6.1%)		9/73 (12.3%)
Back pain	5/33 (15.2%)		5/73 (6.8%)
Muscle spasms	1/33 (3%)		5/73 (6.8%)
Musculoskeletal pain	1/33 (3%)		5/73 (6.8%)
Myalgia	3/33 (9.1%)		6/73 (8.2%)
Osteopenia	2/33 (6.1%)		0/73 (0%)
Osteoporosis	2/33 (6.1%)		2/73 (2.7%)
Pain in extremity	4/33 (12.1%)		4/73 (5.5%)
Nervous system disorders
Dizziness	3/33 (9.1%)		7/73 (9.6%)
Headache	6/33 (18.2%)		10/73 (13.7%)
Psychiatric disorders
Abnormal dreams	1/33 (3%)		4/73 (5.5%)
Depression	2/33 (6.1%)		3/73 (4.1%)
Insomnia	7/33 (21.2%)		6/73 (8.2%)
Renal and urinary disorders
Haematuria	1/33 (3%)		6/73 (8.2%)
Nephrolithiasis	2/33 (6.1%)		2/73 (2.7%)
Renal cyst	2/33 (6.1%)		1/73 (1.4%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/33 (0%)		4/73 (5.5%)
Respiratory, thoracic and mediastinal disorders
Cough	2/33 (6.1%)		8/73 (11%)
Hiccups	2/33 (6.1%)		0/73 (0%)
Oropharyngeal pain	2/33 (6.1%)		2/73 (2.7%)
Skin and subcutaneous tissue disorders
Acne	2/33 (6.1%)		0/73 (0%)
Actinic keratosis	0/33 (0%)		4/73 (5.5%)
Dry skin	2/33 (6.1%)		0/73 (0%)
Pruritus	2/33 (6.1%)		1/73 (1.4%)
Rash	2/33 (6.1%)		8/73 (11%)
Skin lesion	0/33 (0%)		5/73 (6.8%)
Vascular disorders
Hypertension	2/33 (6.1%)		5/73 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years