Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01818596

Collaborator

(none)

252

Enrollment

Locations

Arm

63.7

Actual Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the effect of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) tablet on renal parameters at Week 24 in treatment-naive and treatment-experienced HIV-positive, adults with mild to moderate renal impairment.

Condition or Disease	Intervention/Treatment	Phase
HIV HIV Infections	Drug: E/C/F/TAF	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

252 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

Actual Study Start Date :

Mar 27, 2013

Actual Primary Completion Date :

Jul 31, 2014

Actual Study Completion Date :

Jul 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E/C/F/TAF Participants will receive E/C/F/TAF for 144 weeks. Following Week 144, in countries where E/C/F/TAF is not available (except for the United Kingdom), participants will be given the option to continue in the study and receive E/C/F/TAF for another 48 weeks, or until the product becomes available through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.	Drug: E/C/F/TAF E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food Other Names: Genvoya®

Arm

Intervention/Treatment

Experimental: E/C/F/TAF

Participants will receive E/C/F/TAF for 144 weeks. Following Week 144, in countries where E/C/F/TAF is not available (except for the United Kingdom), participants will be given the option to continue in the study and receive E/C/F/TAF for another 48 weeks, or until the product becomes available through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.

Drug: E/C/F/TAF

E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food

Other Names:

Genvoya®

Outcome Measures

Primary Outcome Measures

Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24 [Baseline; Week 24]
eGFR is a measurement of the kidney's ability to filter blood.
Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24 [Baseline; Week 24]
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24 [Baseline; Week 24]
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.

Secondary Outcome Measures

Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy [Baseline; Week 2, 4, or 8; Week 24]
aGFR was directly measured using iohexol plasma clearance (CLiohexol).
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48 [Baseline; Weeks 24 and 48]
CTX is a biomarker of bone turnover.
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48 [Baseline; Weeks 24 and 48]
P1NP is a biomarker of bone turnover.
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 [Baseline; Weeks 24, 48, 96, and 144]
Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 [Baseline; Weeks 24, 48, 96, and 144]
Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury.
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities [Baseline up to Week 240 plus 30 days]
Adverse events (AEs) and graded laboratory abnormalities occurring during the E/C/F/TAF treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 [Weeks 24, 48, 96, and 144]
The percentage of participants achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Pharmacokinetic (PK) Parameter: Cmax of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
Cmax is defined as the maximum concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: Tmax of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
Tmax is defined as the time of Cmax. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: Clast of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
Clast is defined as the last observable concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: Tlast of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
Tlast is defined as the time of Clast. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: λz of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
λz is defined as the terminal elimination rate constant. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: AUCtau of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: t1/2 of TAF [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study [Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose]
TFV-DP is an active phosphorylated metabolite of tenofovir alafenamide. AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 [Baseline; Weeks 48, 96, and 144]
eGFR is a measurement of the kidney's ability to filter blood.
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 [Baseline; Weeks 48, 96, and 144]
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 [Baseline; Weeks 48, 96, and 144]
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Cohort 1 (treatment-experienced switch)

Must not have a history of known resistance to elvitegravir (EVG), tenofovir disoproxil fumarate (TDF), or emtricitabine (FTC)
Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels (according to the local assay being used) in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
Estimated glomerular filtration rate (GFR) 30-69 mL/min according to the Cockcroft-Gault formula for creatinine clearance, using actual weight
May be currently enrolled in Gilead studies GS-US-236-0102, GS-US-236-0103, and GS-US-216-0114, but will be eligible to enroll only after the Week 144 visit for that study is complete; or currently receiving Stribild® (STB) or atazanavir (ATV)/cobicistat (COBI) + Truvada (TVD) in Gilead studies GS-US-236-0104 or GS-US-216-0105, but will be eligible to enroll only after the Week 48 visit for that study is complete.

Cohort 2 (treatment-naive)

Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
Screening genotype report provided by Gilead Sciences must show sensitivity to EVG, FTC, and TDF
No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PrEP), or post-exposure prophylaxis (PEP), up to 6 months prior to screening
Estimated GFR 30-69 mL/min according to the Cockcroft Gault formula for creatinine clearance, using actual weight

All Cohorts:

All individuals must meet all of the following inclusion criteria to be eligible for participation in this study:

The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
CD4+ count of ≥ 50 cells/μL
Stable renal function: serum creatinine measurements to be taken at least once (within three months of screening)
Cause of underlying chronic kidney disease (eg hypertension, diabetes) stable, without change in medical management, for 3 months prior to baseline
Normal electrocardiogram (ECG)
Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
Adequate hematologic function
Serum amylase ≤ 5 x ULN
Females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence) from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product. A highly effective method of contraception is defined as two separate forms of contraception, one of which must be an effective barrier method, or males must be non-heterosexually active, or practice sexual abstinence

Key Exclusion Criteria:

A new AIDS-defining condition (excluding CD4 cell count and percentage criteria) diagnosed within the 30 days prior to screening,with the exception of the first two bullet points
Hepatitis C virus (HCV) antibody positive. Individuals who are HCV positive, but have a documented negative HCV RNA, are eligible
Hepatitis B surface antigen (HBVsAg) positive
Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study
Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, etc.)
Females who are breastfeeding
Positive serum pregnancy test
Have an implanted defibrillator or pacemaker
Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
Individuals on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone and dexamethasone)
Individuals receiving ongoing therapy with any medications not to be used with EVG, COBI, FTC, or TAF or individuals with any known allergies to the excipients of E/C/F/TAF

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maricopa Integrated Health System - McDowell Clinic	Phoenix	Arizona	United States	85006
2	Pueblo Family Physicians	Phoenix	Arizona	United States	85015
3	Health for Life Clinic PLLC	Little Rock	Arkansas	United States	72207
4	Pacific Oaks Medical Group	Beverly Hills	California	United States	90211
5	Kaiser Permanente	Hayward	California	United States	94545
6	Long Beach Education and Research Consultants	Long Beach	California	United States	90813
7	LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic	Los Angeles	California	United States	90028
8	Peter J Ruane, MD, Inc	Los Angeles	California	United States	90036
9	Anthony Mills MD, Inc	Los Angeles	California	United States	90069
10	Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group	Palm Springs	California	United States	92262
11	Kaiser Permanente Medical Group	Sacramento	California	United States	95825
12	Metropolis Medical	San Francisco	California	United States	94109
13	Kaiser Permanente CTU San Francisco	San Francisco	California	United States	94118
14	University of Colorado	Aurora	Colorado	United States	80045
15	National Jewish Health	Denver	Colorado	United States	80206
16	Dupont Circle Physician's Group	Washington	District of Columbia	United States	20009
17	Gary J. Richmond, MD PA	Fort Lauderdale	Florida	United States	33316
18	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982
19	Idocf/Valuhealthmd	Orlando	Florida	United States	32806
20	University of South Florida	Tampa	Florida	United States	33602
21	Triple O Research Institute, P.A.	West Palm Beach	Florida	United States	33401
22	Rowan Tree Medical, P.A.	Wilton Manors	Florida	United States	33305
23	Infectious Disease Specialists of Atlanta	Decatur	Georgia	United States	30033
24	Mercer University	Macon	Georgia	United States	31210
25	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
26	Community Research Initiative of New England	Boston	Massachusetts	United States	02111
27	The Research Institute	Springfield	Massachusetts	United States	01105
28	Be Well Medical Center, P.C.	Berkley	Michigan	United States	48210
29	Henry Ford Health System	Detroit	Michigan	United States	48202
30	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
31	The Kansas City Care Clinic (KC Free Health Clinic)	Kansas City	Missouri	United States	64111
32	Southampton Healthcare, Inc.	Saint Louis	Missouri	United States	63139
33	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07754
34	Saint Michael's Medical Center	Newark	New Jersey	United States	07102
35	Southwest CARE Center	Santa Fe	New Mexico	United States	87505
36	Albany Medical College	Albany	New York	United States	12208
37	Upstate Infectious Diseases Associates	Albany	New York	United States	12208
38	Jacobi Medical Center	Bronx	New York	United States	10461
39	Montefiore Medical Center	Bronx	New York	United States	10467
40	North Shore University Hospital/Division of Infectious Diseases	Manhasset	New York	United States	11030
41	Aids Care	Rochester	New York	United States	14607
42	University of Cincinnati	Cincinnati	Ohio	United States	45267-0405
43	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
44	University of PA HIV Clinical Trials Unit	Philadelphia	Pennsylvania	United States	19104
45	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
46	St. Hope Foundation	Bellaire	Texas	United States	77401
47	North Texas Infectious Diseases Consultants, PA	Dallas	Texas	United States	75246
48	Garcias' Family Health Group	Harlingen	Texas	United States	78550
49	Therapeutic Concepts, PA	Houston	Texas	United States	77004
50	Gordon E. Crofoot MD, PA	Houston	Texas	United States	77098
51	Peter Shalit, MD	Seattle	Washington	United States	98104
52	Holdsworth House Medical Practice	Darlinghurst	New South Wales	Australia	2010
53	Clinical Research Infectious Diseases Department- Alfred Hospital	Melbourne	Victoria	Australia	3004
54	Prahran Market Clinic	Prahran	Victoria	Australia	3181
55	Instituto Dominicano de Estudios Virologicos (IDEV)	Santo Domingo		Dominican Republic	99999
56	Hopital de la Croix Rousse	Lyon		France	69004
57	GHPS Service des maladies infectieuses et tropicales pavillon Laveran unité de recherche clinique	Paris		France	75651
58	Hospital Civil de Guadalajara Dr. Juan I. Menchaca	Guadalajara	Jalisco	Mexico	44340
59	University Medical Center Utrecht	Utrecht		Netherlands	3584 CX
60	Hospital Universitari de Bellvitge	Barcelona		Spain	8907
61	Germans Trias i Pujol University Hospital	Barcelona		Spain	8916
62	Hospital La Paz	Madrid		Spain	28046
63	HIV-NAT, Thai Red Cross AIDS Research Centre	Bangkok		Thailand	10330
64	Faculty of Medicine Ramathibodi Hospital, Mahidol University	Bangkok		Thailand	10400
65	Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital	Bangkok		Thailand	10700
66	Srinagarind Hospital, Khon Kaen University	Khon Kaen		Thailand	40002
67	Brighton & Sussex University Hospitals NHS Trust	Brighton		United Kingdom	BN2 1ES
68	Kings College London	London		United Kingdom	SE5 9RJ
69	Chelsea and Westminster NHS Foundation Trust Hospital	London		United Kingdom	Sw10 9NH
70	Central Manchester University Hospitals NHS foundation Trust	Manchester		United Kingdom	M13 0FH

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01818596

Other Study ID Numbers:

GS-US-292-0112
2013-000516-25

First Posted:

Mar 26, 2013

Last Update Posted:

Mar 2, 2020

Last Verified:

Jun 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Gilead Sciences

HIV

HIV-1 Infected

Treatment Experienced

Treatment Naive

Additional relevant MeSH terms:

HIV Infections

Renal Insufficiency

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in North America, Australia, Asia, and Europe. The first participant was screened on 27 March 2013. The last study visit occurred on 18 July 2018.
Pre-assignment Detail	380 participants were screened.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet administered orally once daily with food for up to 240 weeks in antiretroviral treatment (ART)-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Period Title: Overall Study
STARTED	246	6
COMPLETED	215	6
NOT COMPLETED	31	0

Baseline Characteristics

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)	Total
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants	Total of all reporting groups
Overall Participants	242	6	248
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (9.9)	55 (7.1)	58 (9.8)
Sex: Female, Male (Count of Participants)
Female	50 20.7%	0 0%	50 20.2%
Male	192 79.3%	6 100%	198 79.8%
Race/Ethnicity, Customized (Count of Participants)
Asian	34 14%	1 16.7%	35 14.1%
American Indian or Alaska Native	1 0.4%	0 0%	1 0.4%
Black or African American	44 18.2%	3 50%	47 19%
Native Hawaiian or Pacific Islander	2 0.8%	0 0%	2 0.8%
White	152 62.8%	2 33.3%	154 62.1%
Other	7 2.9%	0 0%	7 2.8%
Not Permitted	2 0.8%	0 0%	2 0.8%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	31 12.8%	1 16.7%	32 12.9%
Not Hispanic or Latino	209 86.4%	5 83.3%	214 86.3%
Not Permitted	2 0.8%	0 0%	2 0.8%
Region of Enrollment (Count of Participants)
United States	166 68.6%	5 83.3%	171 69%
United Kingdom	5 2.1%	0 0%	5 2%
Thailand	30 12.4%	1 16.7%	31 12.5%
Spain	13 5.4%	0 0%	13 5.2%
Netherlands	2 0.8%	0 0%	2 0.8%
Dominican Republic	6 2.5%	0 0%	6 2.4%
Mexico	2 0.8%	0 0%	2 0.8%
Australia	12 5%	0 0%	12 4.8%
France	6 2.5%	0 0%	6 2.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
Description	eGFR is a measurement of the kidney's ability to filter blood.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set (enrolled and received at least 1 dose of study drug) with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Baseline	55.6	60.2
Change at Week 24	-0.4	-0.3

2. Primary Outcome

Title	Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24
Description	eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Baseline	69.7	70.2
Change at Week 24	3.8	3.9

3. Primary Outcome

Title	Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
Description	eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.
Time Frame	Baseline; Week 24

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Baseline	54.1	54.4
Change at Week 24	-1.8	-2.6

4. Secondary Outcome

Title	Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy
Description	aGFR was directly measured using iohexol plasma clearance (CLiohexol).
Time Frame	Baseline; Week 2, 4, or 8; Week 24

Outcome Measure Data

Analysis Population Description
Participants in the Pharmacodynamic (PD) Substudy Analysis Set (enrolled in the pharmacokinetic (PK)/PD substudy, received at least 1 dose of study drug, and had baseline and at least 1 postbaseline assessment for aGFR assessed by CLiohexol) with available data at the respective time point were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	32
Baseline	60.1 (19.06)
Change at Week 2, 4, or 8	-0.6 (8.45)
Change at Week 24	1.4 (9.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1 (Treatment-experienced)
	Comments	Comparison is made between the baseline value and the value from the Week 2, 4, or 8 visit and presented as a geometric least squares mean (GLSM) ratio with 90% confidence interval (CI). Postbaseline value and baseline value were used as test and reference, respectively.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	30 participants with evaluable aGFR (measured by iohexol clearance) in either cohort would provide at least 90% power to show that aGFR change is < 20% after participants were administered E/C/F/TAF. In this sample size/power computation, it was assumed that the intra-participant variation for aGFR is 0.17 mL/min on natural logarithm scale and a clinical meaningful boundary in aGFR change is 80% to 125%.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference in GLSM Ratio
	Estimated Value	98.94
	Confidence Interval	(2-Sided) 90% 93.71 to 104.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	A parametric analysis of variance model using a mixed-effects model with repeated statement was fitted to the natural logarithm transferred aGFR obtained at postbaseline visits and baseline.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 1 (Treatment-experienced)
	Comments	Comparison is made between the baseline value and the value from the Week 24 visit and presented as a GLSM ratio with 90% CI. Week 24 value and baseline value were used as test and reference, respectively.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	30 participants with evaluable aGFR (measured by iohexol clearance) in either cohort would provide at least 90% power to show that aGFR change is < 20% after participants were administered E/C/F/TAF. In this sample size/power computation, it was assumed that the intra-participant variation for aGFR is 0.17 mL/min on natural logarithm scale and a clinical meaningful boundary in aGFR change is 80% to 125%.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference in GLSM Ratio
	Estimated Value	102.66
	Confidence Interval	(2-Sided) 90% 97.11 to 108.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	A parametric analysis of variance model using a mixed-effects model with repeated statement was fitted to the natural logarithm transferred aGFR obtained at postbaseline visits and baseline.

5. Secondary Outcome

Title	Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48
Description	CTX is a biomarker of bone turnover.
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	226	6
Change at Week 24	-3.9	16.9
Change at Week 48	-2.2	0.0

6. Secondary Outcome

Title	Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48
Description	P1NP is a biomarker of bone turnover.
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	229	6
Change at Week 24	-12.98	6.44
Change at Week 48	-25.29	2.27

7. Secondary Outcome

Title	Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
Description	Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.
Time Frame	Baseline; Weeks 24, 48, 96, and 144

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	227	6
Change at Week 24	-56.2	68.8
Change at Week 48	-68.9	47.8
Change at Week 96	-64.1	55.0
Change at Week 144	-63.8	-1.0

8. Secondary Outcome

Title	Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
Description	Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury.
Time Frame	Baseline; Weeks 24, 48, 96, and 144

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	224	6
Change at Week 24	-70.7	-19.5
Change at Week 48	-76.5	-59.2
Change at Week 96	-83.6	-45.9
Change at Week 144	-81.9	-3.6

9. Secondary Outcome

Title	Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities
Description	Adverse events (AEs) and graded laboratory abnormalities occurring during the E/C/F/TAF treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time Frame	Baseline up to Week 240 plus 30 days

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Any AE	95.5 39.5%	100.0 1666.7%
Grade 3 or 4 AE	22.3 9.2%	16.7 278.3%
AE leading to drug discontinuation	5.0 2.1%	0 0%
Serious AE	22.7 9.4%	16.7 278.3%
Grade 3 or 4 laboratory abnormality	42.6 17.6%	66.7 1111.7%

10. Secondary Outcome

Title	Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144
Description	The percentage of participants achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame	Weeks 24, 48, 96, and 144

Outcome Measure Data

Analysis Population Description
Full Analysis Set included participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Week 24	95.0 39.3%	83.3 1388.3%
Week 48	93.0 38.4%	100.0 1666.7%
Week 96	88.4 36.5%	100.0 1666.7%
Week 144	81.4 33.6%	100.0 1666.7%

11. Secondary Outcome

Title	Pharmacokinetic (PK) Parameter: Cmax of TAF
Description	Cmax is defined as the maximum concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set (enrolled in the PK/PD substudy, received at least 1 dose of study drug, and for whom steady-state PK parameters were available) with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Mean (Standard Deviation) [ng/mL]	269.8 (180.77)

12. Secondary Outcome

Title	PK Parameter: Tmax of TAF
Description	Tmax is defined as the time of Cmax. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Median (Inter-Quartile Range) [hours]	0.97

13. Secondary Outcome

Title	PK Parameter: Clast of TAF
Description	Clast is defined as the last observable concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Mean (Standard Deviation) [ng/mL]	7.6 (25.73)

14. Secondary Outcome

Title	PK Parameter: Tlast of TAF
Description	Tlast is defined as the time of Clast. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Median (Inter-Quartile Range) [hours]	4.45

15. Secondary Outcome

Title	PK Parameter: λz of TAF
Description	λz is defined as the terminal elimination rate constant. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Mean (Standard Deviation) [1/hour]	1.764 (1.4521)

16. Secondary Outcome

Title	PK Parameter: AUCtau of TAF
Description	AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Mean (Standard Deviation) [ng*h/mL]	368.4 (631.20)

17. Secondary Outcome

Title	PK Parameter: t1/2 of TAF
Description	t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	30
Median (Inter-Quartile Range) [hours]	0.43

18. Secondary Outcome

Title	PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study
Description	TFV-DP is an active phosphorylated metabolite of tenofovir alafenamide. AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame	Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose

Outcome Measure Data

Analysis Population Description
Participants who were enrolled in the PK/PD substudy, received at least 1 dose of study drug, and for whom the steady-state PK parameter (AUCtau) of TFV-DP was evaluable were analyzed.

Arm/Group Title	Substudy Participants
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Measure Participants	23
Mean (Standard Deviation) [µmol*h/L]	50.6 (55.75)

19. Secondary Outcome

Title	Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144
Description	eGFR is a measurement of the kidney's ability to filter blood.
Time Frame	Baseline; Weeks 48, 96, and 144

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Baseline	55.6	60.2
Change at Week 48	-0.6	-0.6
Change at Week 96	0.6	-1.9
Change at Week 144	1.5	7.0

20. Secondary Outcome

Title	Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144
Description	eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Time Frame	Baseline; Weeks 48, 96, and 144

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Baseline	69.7	70.2
Change at Week 48	1.7	7.3
Change at Week 96	3.2	5.6
Change at Week 144	3.1	3.5

21. Secondary Outcome

Title	Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144
Description	eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.
Time Frame	Baseline; Weeks 48, 96, and 144

Outcome Measure Data

Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.

Arm/Group Title	Cohort 1 (Treatment-experienced)	Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Measure Participants	242	6
Baseline	54.1	54.4
Change at Week 48	-1.7	-3.0
Change at Week 96	0.1	-3.1
Change at Week 144	1.7	0.9

Adverse Events

	Cohort 1 (Treatment-experienced)		Cohort 2 (Treatment-naive)
Time Frame	First dose date up to Week 240 plus 30 days
Adverse Event Reporting Description	Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Cohort 1 (Treatment-experienced)		Cohort 2 (Treatment-naive)
Arm/Group Description	E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants		E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1 (Treatment-experienced)		Cohort 2 (Treatment-naive)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/242 (22.7%)		1/6 (16.7%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/242 (0.4%)		0/6 (0%)
Cardiac disorders
Acute coronary syndrome	1/242 (0.4%)		0/6 (0%)
Acute myocardial infarction	4/242 (1.7%)		0/6 (0%)
Cardiac arrest	1/242 (0.4%)		0/6 (0%)
Cardiac failure congestive	2/242 (0.8%)		0/6 (0%)
Cardio-respiratory arrest	1/242 (0.4%)		0/6 (0%)
Myocardial infarction	1/242 (0.4%)		0/6 (0%)
Palpitations	1/242 (0.4%)		0/6 (0%)
Supraventricular extrasystoles	1/242 (0.4%)		0/6 (0%)
Eye disorders
Blindness unilateral	1/242 (0.4%)		0/6 (0%)
Vitreous detachment	1/242 (0.4%)		0/6 (0%)
Gastrointestinal disorders
Abdominal pain	2/242 (0.8%)		0/6 (0%)
Abdominal pain upper	1/242 (0.4%)		0/6 (0%)
Colitis	1/242 (0.4%)		0/6 (0%)
Dysphagia	1/242 (0.4%)		0/6 (0%)
Large intestinal obstruction	1/242 (0.4%)		0/6 (0%)
Pancreatitis acute	1/242 (0.4%)		0/6 (0%)
Hepatobiliary disorders
Bile duct stone	1/242 (0.4%)		0/6 (0%)
Cholecystitis	1/242 (0.4%)		0/6 (0%)
Infections and infestations
Abscess neck	1/242 (0.4%)		0/6 (0%)
Acute hepatitis c	1/242 (0.4%)		0/6 (0%)
Appendicitis	1/242 (0.4%)		0/6 (0%)
Bronchitis	2/242 (0.8%)		0/6 (0%)
Clostridium difficile colitis	1/242 (0.4%)		0/6 (0%)
Device related infection	1/242 (0.4%)		0/6 (0%)
Endophthalmitis	1/242 (0.4%)		0/6 (0%)
Gastroenteritis	2/242 (0.8%)		0/6 (0%)
Gastrointestinal viral infection	1/242 (0.4%)		0/6 (0%)
Influenza	1/242 (0.4%)		0/6 (0%)
Localised infection	1/242 (0.4%)		0/6 (0%)
Ophthalmic herpes zoster	1/242 (0.4%)		0/6 (0%)
Pneumonia	4/242 (1.7%)		0/6 (0%)
Pneumonia bacterial	1/242 (0.4%)		0/6 (0%)
Pneumonia staphylococcal	1/242 (0.4%)		0/6 (0%)
Pyelonephritis acute	1/242 (0.4%)		0/6 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/242 (0.4%)		0/6 (0%)
Fall	1/242 (0.4%)		0/6 (0%)
Rib fracture	1/242 (0.4%)		0/6 (0%)
Spinal compression fracture	1/242 (0.4%)		0/6 (0%)
Sternal fracture	1/242 (0.4%)		0/6 (0%)
Investigations
Weight decreased	1/242 (0.4%)		0/6 (0%)
Metabolism and nutrition disorders
Dehydration	3/242 (1.2%)		0/6 (0%)
Hyperglycaemia	1/242 (0.4%)		0/6 (0%)
Hypoglycaemia	1/242 (0.4%)		0/6 (0%)
Hypovolaemia	1/242 (0.4%)		0/6 (0%)
Type 2 diabetes mellitus	2/242 (0.8%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/242 (0.8%)		0/6 (0%)
Osteonecrosis	1/242 (0.4%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	1/242 (0.4%)		0/6 (0%)
Invasive ductal breast carcinoma	1/242 (0.4%)		0/6 (0%)
Lung neoplasm malignant	1/242 (0.4%)		0/6 (0%)
Malignant neoplasm of unknown primary site	1/242 (0.4%)		0/6 (0%)
Renal cell carcinoma	1/242 (0.4%)		0/6 (0%)
Transitional cell carcinoma	1/242 (0.4%)		0/6 (0%)
Nervous system disorders
Cervical radiculopathy	1/242 (0.4%)		0/6 (0%)
Facial paralysis	1/242 (0.4%)		0/6 (0%)
Loss of consciousness	1/242 (0.4%)		0/6 (0%)
Syncope	2/242 (0.8%)		0/6 (0%)
Transient ischaemic attack	1/242 (0.4%)		0/6 (0%)
Psychiatric disorders
Drug dependence	1/242 (0.4%)		0/6 (0%)
Major depression	1/242 (0.4%)		0/6 (0%)
Suicidal ideation	0/242 (0%)		1/6 (16.7%)
Suicide attempt	1/242 (0.4%)		0/6 (0%)
Renal and urinary disorders
Acute kidney injury	2/242 (0.8%)		0/6 (0%)
Chronic kidney disease	1/242 (0.4%)		0/6 (0%)
Urinary retention	1/242 (0.4%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	2/242 (0.8%)		0/6 (0%)
Pulmonary embolism	1/242 (0.4%)		0/6 (0%)
Vascular disorders
Deep vein thrombosis	1/242 (0.4%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (Treatment-experienced)		Cohort 2 (Treatment-naive)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	195/242 (80.6%)		5/6 (83.3%)
Cardiac disorders
Supraventricular extrasystoles	1/242 (0.4%)		1/6 (16.7%)
Gastrointestinal disorders
Constipation	16/242 (6.6%)		0/6 (0%)
Diarrhoea	32/242 (13.2%)		1/6 (16.7%)
Gingival pain	0/242 (0%)		1/6 (16.7%)
Mouth ulceration	2/242 (0.8%)		1/6 (16.7%)
Nausea	22/242 (9.1%)		0/6 (0%)
Vomiting	13/242 (5.4%)		0/6 (0%)
General disorders
Chest pain	10/242 (4.1%)		1/6 (16.7%)
Fatigue	20/242 (8.3%)		1/6 (16.7%)
Peripheral swelling	8/242 (3.3%)		1/6 (16.7%)
Infections and infestations
Bronchitis	37/242 (15.3%)		1/6 (16.7%)
Hordeolum	1/242 (0.4%)		1/6 (16.7%)
Influenza	10/242 (4.1%)		1/6 (16.7%)
Nasopharyngitis	25/242 (10.3%)		0/6 (0%)
Sinusitis	18/242 (7.4%)		0/6 (0%)
Upper respiratory tract infection	39/242 (16.1%)		1/6 (16.7%)
Urinary tract infection	25/242 (10.3%)		0/6 (0%)
Injury, poisoning and procedural complications
Exposure to communicable disease	1/242 (0.4%)		1/6 (16.7%)
Investigations
Cardiac murmur	1/242 (0.4%)		1/6 (16.7%)
Electrocardiogram st-t change	0/242 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
Dyslipidaemia	5/242 (2.1%)		1/6 (16.7%)
Hyperlipidaemia	7/242 (2.9%)		2/6 (33.3%)
Hypokalaemia	3/242 (1.2%)		1/6 (16.7%)
Vitamin d deficiency	4/242 (1.7%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	34/242 (14%)		1/6 (16.7%)
Arthritis	3/242 (1.2%)		1/6 (16.7%)
Back pain	27/242 (11.2%)		0/6 (0%)
Osteopenia	26/242 (10.7%)		0/6 (0%)
Osteoporosis	13/242 (5.4%)		1/6 (16.7%)
Pain in extremity	25/242 (10.3%)		2/6 (33.3%)
Tendonitis	5/242 (2.1%)		1/6 (16.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	1/242 (0.4%)		1/6 (16.7%)
Nervous system disorders
Dizziness	18/242 (7.4%)		0/6 (0%)
Headache	20/242 (8.3%)		1/6 (16.7%)
Migraine	2/242 (0.8%)		1/6 (16.7%)
Paraesthesia	13/242 (5.4%)		0/6 (0%)
Somnolence	3/242 (1.2%)		1/6 (16.7%)
Renal and urinary disorders
Proteinuria	3/242 (1.2%)		1/6 (16.7%)
Renal cyst	14/242 (5.8%)		0/6 (0%)
Reproductive system and breast disorders
Erectile dysfunction	6/242 (2.5%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	24/242 (9.9%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Dermatitis	4/242 (1.7%)		1/6 (16.7%)
Pruritus	4/242 (1.7%)		1/6 (16.7%)
Rash	15/242 (6.2%)		0/6 (0%)
Rash generalised	1/242 (0.4%)		1/6 (16.7%)
Vascular disorders
Hypertension	24/242 (9.9%)		0/6 (0%)
Orthostatic hypotension	1/242 (0.4%)		1/6 (16.7%)

Limitations/Caveats

Enrollment in Cohort 2 (treatment-naive) was low, which affects the interpretation of the data.

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

Results Point of Contact

Name/Title	Gilead Clinical Study Information Center
Organization	Gilead Sciences
Phone	1-833-445-3230 (GILEAD-0)
Email	GileadClinicalTrials@gilead.com

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01818596

Other Study ID Numbers:

GS-US-292-0112
2013-000516-25

First Posted:

Mar 26, 2013

Last Update Posted:

Mar 2, 2020

Last Verified:

Jun 1, 2019

Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Key Inclusion Criteria:

All Cohorts:

Key Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact