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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01363011

Enrollment

106

Registered

2011-06-01

Start date

2011-05-31

Completion date

2015-02-28

Last updated

2016-05-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acquired Immunodeficiency Syndrome, HIV Infections

Keywords

HIV-1, Treatment Naive, Treatment Experienced

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.

Interventions

DRUGE/C/F/TDF

E/C/F/TDF (150/150/200/300 mg) STR administered orally once daily

DRUGCOBI

COBI 150 mg tablet administered with food orally once daily

DRUGATV

ATV 300 mg tablet administered orally once daily

DRUGDRV

DRV 800 mg tablet administered orally once daily

DRUGNRTI

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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Measure	Time frame	Description
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.
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.
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.
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Countries

Australia, Austria, Canada, Dominican Republic, Germany, Mexico, Puerto Rico, United Kingdom, United States

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 details

177 participants were screened.

Participants by arm

Arm	Count
E/C/F/TDF (Cohort 1) 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.	33
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 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.	73
Total	106

Withdrawals & dropouts

Period	Reason	FG000	FG001
Extension Phase	Adverse Event	1	1
Extension Phase	Investigator's Discretion	2	2
Extension Phase	Lack of Efficacy	0	1
Extension Phase	Lost to Follow-up	0	2
Extension Phase	Rolled Over to Another Gilead Study	2	1
Extension Phase	Withdrew Consent	0	1
Main Study	Adverse Event	2	3
Main Study	Investigator's Discretion	1	1
Main Study	Protocol Violation	0	1
Main Study	Withdrew Consent	1	4

Baseline characteristics

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

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	31 / 33	66 / 73
serious Total, serious adverse events	6 / 33	11 / 73

Outcome results

Primary

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

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

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.

Arm	Measure	Group	Value (NUMBER)
E/C/F/TDF (Cohort 1)	Change From Baseline in Actual Glomerular Filtration Rate (aGFR) at Weeks 2, 4, and 24 (Cohort 1)	Baseline	81.6 mL/min
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)

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

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.

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)	Baseline	82.5 mL/min
E/C/F/TDF (Cohort 1)	Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)	Change at Week 2 (n=13)	1.6 mL/min
E/C/F/TDF (Cohort 1)	Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)	Change at Week 4 (n=13)	7.0 mL/min
E/C/F/TDF (Cohort 1)	Change From Baseline in aGFR at Weeks 2, 4, and 24 (Cohort 2)	Change at Week 24 (n=11)	-4.1 mL/min

Primary

Change From Baseline in eGFR-CG at Week 24 (Cohort 2)

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

Time frame: 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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-CG at Week 24 (Cohort 2)	Baseline (n = 73)	71.4 mL/min
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-CG at Week 24 (Cohort 2)	Change at Week 24 (n = 67)	-3.7 mL/min

Primary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 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

Primary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Primary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Primary

Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-MDRD at Week 24 (Cohort 2)	Baseline (n = 73)	65.8 mL/min/1.73 m^2
E/C/F/TDF (Cohort 1)	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

Primary

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 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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Primary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Primary

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

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

Time frame: 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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 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

Primary

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

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

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

Arm	Measure	Value (NUMBER)
E/C/F/TDF (Cohort 1)	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 1)	84.8 percentage of participants

Primary

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

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

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

Arm	Measure	Value (NUMBER)
E/C/F/TDF (Cohort 1)	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 (Cohort 2)	90.4 percentage of participants

Secondary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)	Change at Week 48 (n = 28)	-7.6 mL/min
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 1)	Change at Week 96 (n = 25)	-7.9 mL/min

Secondary

Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)	Change at Week 48 (n = 63)	-3.8 mL/min
E/C/F/TDF (Cohort 1)	Change From Baseline in eGFR-CG at Weeks 48 and 96 (Cohort 2)	Change at Week 96 (n = 50)	-5.0 mL/min

Secondary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Secondary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Secondary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Secondary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Secondary

Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 1)

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Secondary

Change From Baseline in eGFR-MDRD at Weeks 48 and 96 (Cohort 2)

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

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

Arm	Measure	Group	Value (MEDIAN)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Secondary

Percentage of Participants Who Experienced Adverse Events (Cohort 1)

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

Population: Safety Analysis Set (treatment-naive only)

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

Secondary

Percentage of Participants Who Experienced Adverse Events (Cohort 2)

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

Population: Safety Analysis Set (treatment-experienced only)

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

Secondary

Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)

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

Population: Safety Analysis Set (treatment-naive only)

Arm	Measure	Group	Value (NUMBER)
E/C/F/TDF (Cohort 1)	Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)	Any laboratory abnormality	100.0 percentage of participants
E/C/F/TDF (Cohort 1)	Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 1)	Grade 3 or 4 laboratory abnormality	39.4 percentage of participants

Secondary

Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)

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

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

Arm	Measure	Group	Value (NUMBER)
E/C/F/TDF (Cohort 1)	Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)	Any laboratory abnormality	100.00 percentage of participants
E/C/F/TDF (Cohort 1)	Percentage of Participants Who Experienced Graded Laboratory Abnormalities (Cohort 2)	Grade 3 or 4 laboratory abnormality	50.0 percentage of participants

Secondary

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

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

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

Arm	Measure	Group	Value (NUMBER)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

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

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

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

Arm	Measure	Group	Value (NUMBER)
E/C/F/TDF (Cohort 1)	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
E/C/F/TDF (Cohort 1)	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

Plasma Pharmacokinetics of COBI: AUCtau (Cohort 1)

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).