Trial Outcomes & Findings for Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment (NCT NCT01363011)

NCT ID: NCT01363011

Last Updated: 2016-05-02

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

106 participants

Primary outcome timeframe

Baseline; Week 24

Results posted on

2016-05-02

Participant Flow

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.

177 participants were screened.

Participant milestones

Participant milestones
Measure	E/C/F/TDF (Cohort 1) 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.	COBI+PI+2 NRTIs (Cohort 2) 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.
Main Study STARTED	33	73
Main Study COMPLETED	29	64
Main Study NOT COMPLETED	4	9
Extension Phase STARTED	18	49
Extension Phase COMPLETED	13	41
Extension Phase NOT COMPLETED	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	E/C/F/TDF (Cohort 1) 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.	COBI+PI+2 NRTIs (Cohort 2) 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.
Main Study Adverse Event	2	3
Main Study Investigator's Discretion	1	1
Main Study Withdrew Consent	1	4
Main Study Protocol Violation	0	1
Extension Phase Adverse Event	1	1
Extension Phase Lack of Efficacy	0	1
Extension Phase Investigator's Discretion	2	2
Extension Phase Withdrew Consent	0	1
Extension Phase Lost to Follow-up	0	2
Extension Phase Rolled Over to Another Gilead Study	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.	COBI+PI+2 NRTIs (Cohort 2) n=73 Participants 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 n=106 Participants Total of all reporting groups
Region of Enrollment Austria	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Australia	1 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Germany	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants	18 participants n=7 Participants	22 participants n=5 Participants
HIV Disease Status Asymptomatic	28 participants n=5 Participants	37 participants n=7 Participants	65 participants n=5 Participants
HIV Disease Status Symptomatic HIV Infection	3 participants n=5 Participants	18 participants n=7 Participants	21 participants n=5 Participants
HIV Disease Status AIDS	2 participants n=5 Participants	18 participants n=7 Participants	20 participants n=5 Participants
Hepatitis B Virus (HBV) Surface Antigen Status Positive	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Age, Continuous	50 years STANDARD_DEVIATION 12.1 • n=5 Participants	54 years STANDARD_DEVIATION 9.5 • n=7 Participants	53 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	60 Participants n=7 Participants	87 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African Heritage	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Race/Ethnicity, Customized White	14 participants n=5 Participants	56 participants n=7 Participants	70 participants n=5 Participants
Race/Ethnicity, Customized Other	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	9 participants n=5 Participants	19 participants n=7 Participants	28 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic/Latino	24 participants n=5 Participants	54 participants n=7 Participants	78 participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	33 participants n=7 Participants	52 participants n=5 Participants
Region of Enrollment Mexico	0 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Canada	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Dominican Republic	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Hepatitis B Virus (HBV) Surface Antigen Status Negative	32 participants n=5 Participants	69 participants n=7 Participants	101 participants n=5 Participants
Hepatitis C Virus (HCV) Antibody Status Positive	2 participants n=5 Participants	10 participants n=7 Participants	12 participants n=5 Participants
Hepatitis C Virus (HCV) Antibody Status Negative	30 participants n=5 Participants	63 participants n=7 Participants	93 participants n=5 Participants
Hepatitis C Virus (HCV) Antibody Status Indeterminate	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
HIV-1 RNA Category < 50 copies/mL	0 participants n=5 Participants	73 participants n=7 Participants	73 participants n=5 Participants
HIV-1 RNA Category ≥ 50 to < 1,000 copies/mL	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
HIV-1 RNA Category ≥ 1,000 to ≤ 100,000 copies/mL	24 participants n=5 Participants	0 participants n=7 Participants	24 participants n=5 Participants
HIV-1 RNA Category > 100,000 copies/mL	9 participants n=5 Participants	0 participants n=7 Participants	9 participants n=5 Participants
CD4 Cell Count ≤ 50 cells/µL	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
CD4 Cell Count 51 to ≤ 200 cells/µL	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
CD4 Cell Count 201 to ≤ 350 cells/µL	13 participants n=5 Participants	5 participants n=7 Participants	18 participants n=5 Participants
CD4 Cell Count 351 to ≤ 500 cells/µL	10 participants n=5 Participants	16 participants n=7 Participants	26 participants n=5 Participants
CD4 Cell Count > 500 cells/µL	6 participants n=5 Participants	49 participants n=7 Participants	55 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1) Baseline (n = 33)	72.9 mL/min Interval 64.7 to 81.1
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1) Change at Week 24 (n = 30)	-5.2 mL/min Interval -13.2 to 1.0

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-CG at Week 24 (Cohort 2) Baseline (n = 73)	71.4 mL/min Interval 61.9 to 80.7
Change From Baseline in eGFR-CG at Week 24 (Cohort 2) Change at Week 24 (n = 67)	-3.7 mL/min Interval -7.4 to 2.0

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1) Baseline (n = 33)	77.1 mL/min/1.73 m^2 Interval 64.3 to 87.2
Change From Baseline in eGFR Using the Modification of Diet in Renal (MDRD) Equation at Week 24 (Cohort 1) Change at Week 24 (n = 30)	-7.4 mL/min/1.73 m^2 Interval -16.3 to -1.2

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2) Baseline (n = 73)	65.8 mL/min/1.73 m^2 Interval 56.2 to 75.2
Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2) Change at Week 24 (n = 67)	-3.4 mL/min/1.73 m^2 Interval -7.5 to 1.9

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
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 (n = 33)	77.6 mL/min/1.73 m^2 Interval 61.7 to 90.5
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) Change at Week 24 (n = 30)	0.3 mL/min/1.73 m^2 Interval -3.3 to 6.1

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2) Baseline (n = 73)	78.6 mL/min/1.73 m^2 Interval 67.0 to 94.4
Change From Baseline in eGFR-CKD-EPI Formula Based on Cystatin C Equation at Week 24 (Cohort 2) Change at Week 24 (n = 67)	-2.7 mL/min/1.73 m^2 Interval -6.8 to 1.9

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1) Baseline (n = 33)	76.9 mL/min/1.73 m^2 Interval 61.7 to 90.1
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 1) Change at Week 24 (n = 30)	0.3 mL/min/1.73 m^2 Interval -3.7 to 5.7

PRIMARY outcome

Timeframe: Baseline; Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2) Baseline (n = 73)	78.2 mL/min/1.73 m^2 Interval 67.1 to 92.4
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation, Adjusted at Week 24 (Cohort 2) Change at Week 24 (n = 67)	-2.8 mL/min/1.73 m^2 Interval -6.7 to 1.9

PRIMARY outcome

Timeframe: Baseline; Weeks 2, 4, and 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=1 Participants 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.
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1) Baseline	81.6 mL/min
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1) Change at Week 2	-12.1 mL/min
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1) Change at Week 4	-7.3 mL/min
Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1) Change at Week 24	-3.3 mL/min

PRIMARY outcome

Timeframe: Baseline; Weeks 2, 4, and 24

Population: 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.

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=14 Participants 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.
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2) Baseline	82.5 mL/min Interval 55.3 to 112.9
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2) Change at Week 2 (n=13)	1.6 mL/min Interval -12.3 to 9.2
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2) Change at Week 4 (n=13)	7.0 mL/min Interval -14.6 to 14.6
Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2) Change at Week 24 (n=11)	-4.1 mL/min Interval -13.5 to 13.2

PRIMARY outcome

Timeframe: Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)	84.8 percentage of participants

PRIMARY outcome

Timeframe: Week 24

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)	90.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1) Change at Week 48 (n = 28)	-7.6 mL/min Interval -12.2 to -2.2
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1) Change at Week 96 (n = 25)	-7.9 mL/min Interval -14.2 to -4.1

SECONDARY outcome

Timeframe: Baseline; Week 48

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2) Change at Week 48 (n = 63)	-3.8 mL/min Interval -9.0 to 0.8
Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2) Change at Week 96 (n = 50)	-5.0 mL/min Interval -13.0 to 0.1

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1) Change at Week 48 (n = 28)	-12.1 mL/min/1.73 m^2 Interval -17.6 to -6.5
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1) Change at Week 96 (n = 25)	-12.9 mL/min/1.73 m^2 Interval -17.7 to -5.4

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2) Change at Week 48 (n = 63)	-3.9 mL/min/1.73 m^2 Interval -8.1 to 1.4
Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2) Change at Week 96 (n = 50)	-2.8 mL/min/1.73 m^2 Interval -13.7 to 2.2

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1) Change at Week 48 (n = 28)	1.9 mL/min/1.73 m^2 Interval -7.1 to 6.9
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 1) Change at Week 96 (n = 25)	12.4 mL/min/1.73 m^2 Interval -0.6 to 20.4

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2) Change at Week 48 (n = 63)	-4.7 mL/min/1.73 m^2 Interval -12.0 to 4.3
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation at Weeks 48 and 96 (Cohort 2) Change at Week 96 (n = 50)	-2.4 mL/min/1.73 m^2 Interval -7.3 to 9.4

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1) Change at Week 48 (n = 28)	1.6 mL/min/1.73 m^2 Interval -8.0 to 6.9
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 1) Change at Week 96 (n = 25)	12.6 mL/min/1.73 m^2 Interval -0.9 to 19.2

SECONDARY outcome

Timeframe: Baseline; Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2) Change at Week 48 (n = 63)	-4.7 mL/min/1.73 m^2 Interval -11.7 to 3.9
Change From Baseline in eGFR-CKD-EPI Based on Cystatin C Equation (Adjusted) at Weeks 48 and 96 (Cohort 2) Change at Week 96 (n = 50)	-2.8 mL/min/1.73 m^2 Interval -7.4 to 8.9

SECONDARY outcome

Timeframe: Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1) Week 48 (n = 33)	78.8 percentage of participants
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 1) Week 96 (n = 27)	88.9 percentage of participants

SECONDARY outcome

Timeframe: Weeks 48 and 96

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

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2) Week 48 (n = 73)	82.2 percentage of participants
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 (Cohort 2) Week 96 (n = 54)	90.7 percentage of participants

SECONDARY outcome

Timeframe: Up to 147 weeks plus 30 days

Population: Safety Analysis Set (treatment-naive only)

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Percentage of Participants Who Experienced Adverse Events (Cohort 1) Any AE	100.0 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 1) Drug-related AE	48.5 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 1) Grade 3 or higher AE	21.2 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 1) AE leading to drug discontinuation	12.1 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 1) Serious AE	18.2 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 1) AE of proximal renal tubulopathy	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 166 weeks plus 30 days

Population: Safety Analysis Set (treatment-experienced only)

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=73 Participants 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.
Percentage of Participants Who Experienced Adverse Events (Cohort 2) Any AE	93.2 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 2) Drug-related AE	27.4 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 2) Grade 3 or higher AE	28.8 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 2) AE leading to drug discontinuation	11.0 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 2) Serious AE	15.1 percentage of participants
Percentage of Participants Who Experienced Adverse Events (Cohort 2) AE of proximal renal tubulopathy	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 147 weeks plus 30 days

Population: Safety Analysis Set (treatment-naive only)

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.

Outcome measures

Outcome measures
Measure	E/C/F/TDF (Cohort 1) n=33 Participants 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.
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1) Any laboratory abnormality	100.0 percentage of participants
Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1) Grade 3 or 4 laboratory abnormality	39.4 percentage of participants

SECONDARY outcome

Timeframe: Up to 166 weeks plus 30 days

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

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.