Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01497899
• Collaborator: (none)
• Enrollment: 279
• Locations: 41
• Arms: 3
• Actual Duration (Months): 55.8
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) FDC in HIV-1 infected, antiretroviral treatment-naive adults.

Condition or Disease	Intervention/Treatment	Phase
Acquired Immunodeficiency Syndrome; HIV Infections	Drug: E/C/F/TDF; Drug: E/C/F/TAF Placebo; Drug: E/C/F/TAF; Drug: E/C/F/TDF Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 279 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
• Actual Study Start Date: Dec 28, 2011
• Actual Primary Completion Date: Oct 17, 2012
• Actual Study Completion Date: Aug 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E/C/F/TAF E/C/F/TAF plus E/C/F/TDF placebo for at least 48 weeks	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya® ; Drug: E/C/F/TDF Placebo; Tablet administered orally once daily
Active Comparator: E/C/F/TDF E/C/F/TDF plus E/C/F/TAF placebo for at least 48 weeks	Drug: E/C/F/TDF; 150/150/200/300 mg FDC tablet administered orally once daily; Other Names: Stribild® ; Drug: E/C/F/TAF Placebo; Tablet administered orally once daily
Experimental: E/C/F/TAF Open-Label Following study unblinding, participants from the E/C/F/TAF and E/C/F/TDF arms may have the option to receive E/C/F/TAF during an open-label extension phase. Also, participants who are actively participating in a Gilead-sponsored study of cobicistat-boosted darunavir plus nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) who have reached the protocol-defined secondary endpoint (Week 48) and remain virologically suppressed are eligible to participate and receive E/C/F/TAF in this open-label extension phase.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya®

Outcome Measures

Primary Outcome Measures

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

   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 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.

Secondary Outcome Measures

1. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [Week 48]

   The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 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.

2. Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 [Baseline; Weeks 24 and 48]

3. Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 [Baseline; Weeks 24 and 48]

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form

• Plasma HIV 1 RNA levels ≥ 5,000 copies/mL

• No prior use of any approved or experimental anti-HIV drug for any length of time

• Screening genotype report must show sensitivity to TDF and emtricitabine (FTC)

• Normal ECG

• Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula

• Hepatic transaminases ≤ 2.5 x upper limit of the normal range (ULN)

• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

• Adequate hematologic function

• CD4+ cell count > 50 cells/µL

• Serum amylase ≤ 5 x ULN

• Normal thyroid-stimulating hormone (TSH)

• Females of childbearing potential must have a negative serum pregnancy test

• 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 drugs

• Female subjects 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

• Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure

• Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level test at screening

• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product

• Age ≥ 18 years

• Life expectancy ≥ 1 year

Key Exclusion Criteria:

• New AIDS-defining condition diagnosed within the 30 days prior to screening

• Hepatitis B surface Antigen positive

• Hepatitis C Antibody positive

• Proven acute hepatitis in the 30 days prior to study entry

• Subjects experiencing decompensated cirrhosis

• Females who are breastfeeding

• Positive serum pregnancy test (female of childbearing potential)

• Have an implanted defibrillator or pacemaker

• Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir and cobicistat

• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study

• Current alcohol or substance

• History of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), 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

• Participation in any other clinical trial without prior approval is prohibited while participating in this trial

• Medications contraindicated for use with emtricitabine or tenofovir disoproxil fumarate

• Any known allergies to the excipients of E/C/F/TAF or E/C/F/TDF FDC tablets

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham (UAB)	Birmingham	Alabama	United States	35233
2	Spectrum Medical Group	Phoenix	Arizona	United States	85012
3	AHF Research Center	Beverly Hills	California	United States	90211
4	Kaiser Permanente	Los Angeles	California	United States	90027
5	Peter J. Ruane, MD, Inc.	Los Angeles	California	United States	90036
6	Anthony Mills MD, Inc	Los Angeles	California	United States	90069
7	East Bay AIDS Center	Oakland	California	United States	94609
8	St. Joseph Heritage Healthcare	Orange	California	United States	92869
9	Stanford University	Palo Alto	California	United States	94304
10	Kaiser Permanente Medical Group	Sacramento	California	United States	95825
11	La Playa Medical Group and Clinical Research	San Diego	California	United States	92103
12	Metropolis Medical	San Francisco	California	United States	94107
13	Kaiser Permanente Medical Group-Clinical Trials Unit	San Francisco	California	United States	94118
14	Apex Research, LLC	Denver	Colorado	United States	80220
15	Dupont Circle Physician's Group	Washington	District of Columbia	United States	20009
16	Whitman-Walker Health	Washington	District of Columbia	United States	20009
17	Capital Medical Associates, PC	Washington	District of Columbia	United States	20036
18	Gary J. Richmond,M.D.,P.A.	Fort Lauderdale	Florida	United States	33316
19	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida	United States	33139
20	Orlando Immunology Center	Orlando	Florida	United States	32803
21	IDOCF/ValuhealthMD, LLC	Orlando	Florida	United States	32806
22	St. Joseph's Comprehensive Research Institute	Tampa	Florida	United States	33614
23	Infectious Disease Specialists of Atlanta	Decatur	Georgia	United States	30033
24	Mercer University Mercer Medicine	Macon	Georgia	United States	31201
25	Howard Brown Health Center	Chicago	Illinois	United States	60613
26	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
27	Be Well Medical Center	Berkley	Michigan	United States	48072
28	Henry Ford Health System	Detroit	Michigan	United States	48202
29	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
30	Central West Clinical Research Inc	Saint Louis	Missouri	United States	63108
31	North Shore University Hospital / Division of Infectious Diseases	Manhasset	New York	United States	11030
32	ID Consultants, P.A.	Charlotte	North Carolina	United States	28209
33	Duke University Medical Center	Durham	North Carolina	United States	27710
34	University of South Carolina School of Medicine Division of Infectious Disease	Columbia	South Carolina	United States	29203
35	Southwest Infectious Disease Clinical Research Inc	Dallas	Texas	United States	75219
36	Tarrant County Infectious Disease Associates	Fort Worth	Texas	United States	76104
37	Therapeutic Concepts, PA	Houston	Texas	United States	77004
38	Gordon E. Crofoot, MD., PA	Houston	Texas	United States	77098
39	DCOL Center for Clinical Research	Longview	Texas	United States	75605
40	Peter Shalit, M.D.	Seattle	Washington	United States	98104
41	Clinical Research Puerto Rico	San Juan		Puerto Rico	00909

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: NCT01497899
• Other Study ID Numbers: GS-US-292-0102
• First Posted: Dec 23, 2011
• Last Update Posted: Nov 19, 2018
• Last Verified: Aug 1, 2017

• 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: No
• Keywords provided by Gilead Sciences: HIV-1; HIV; Treatment-Naive
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States and Puerto Rico. The first participant was screened on 28 December 2011. The last study visit occurred on 22 August 2016.
Pre-assignment Detail	232 participants were screened for the Double-Blind Phase. 108 participants from other Gilead-sponsored Study GS-US-299-0102 joined the Open-Label Extension Phase.

Arm/Group Title	E/C/F/TAF	E/C/F/TDF	D/C/F/TAF to Open-Label E/C/F/TAF	DRV+COBI+TVD to Open-Label E/C/F/TAF
Arm/Group Description	Double-Blind Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet plus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) placebo tablet administered orally once daily for 48 weeks Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Participants previously received darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in another Gilead-sponsored study and then enrolled into the Open-Label Extension Phase of this study to receive E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily.	Participants previously received darunavir (DRV) + cobicistat (COBI) + Truvada® (TVD) in another Gilead-sponsored study and then enrolled into the Open-Label Extension Phase of this study to receive E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily.
Period Title: Double-Blind Phase
STARTED	113	58	0	0
COMPLETED	107	53	0	0
NOT COMPLETED	6	5	0	0
Period Title: Double-Blind Phase
STARTED	105	53	70	38
COMPLETED	86	46	61	33
NOT COMPLETED	19	7	9	5

Baseline Characteristics

Arm/Group Title	E/C/F/TAF	E/C/F/TDF	D/C/F/TAF to Open-Label E/C/F/TAF	DRV+COBI+TVD to Open-Label E/C/F/TAF	Total
Arm/Group Description	Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Participants previously received D/C/F/TAF in another Gilead-sponsored study and then enrolled into the Open-Label Extension Phase of this study to receive E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily.	Participants previously received DRV+COBI+TVD in another Gilead-sponsored study and then enrolled into the Open-Label Extension Phase of this study to receive E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily.	Total of all reporting groups
Overall Participants	112	58	70	38	278
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35 (11.3)	37 (10.6)	36 (11.2)	37 (10.7)	36 (11.0)
Sex: Female, Male (Count of Participants)
Female	4 3.6%	1 1.7%	3 4.3%	3 7.9%	11 4%
Male	108 96.4%	57 98.3%	67 95.7%	35 92.1%	267 96%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
Description	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 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	Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants randomized to the Double-Blind Phase and received at least 1 dose of study drug.

Arm/Group Title	E/C/F/TAF	E/C/F/TDF
Arm/Group Description	Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily
Measure Participants	112	58
Number [percentage of participants]	88.4 78.9%	89.7 154.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	E/C/F/TAF, E/C/F/TDF
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The null hypothesis was that the E/C/F/TAF group was at least 12% lower than the E/C/F/TDF group with respect to the percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24. The alternative hypothesis was that the E/C/F/TAF group was less than 12% lower than the E/C/F/TDF group.
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	P-value comparing the percentages of virologic success was from the Cochran-Mantel-Haenszel (CMH) test stratified by baseline HIV-1 RNA stratum.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -13.5 to 7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentages of virologic success and its 95% confidence interval (CI) were calculated based on baseline HIV-1 RNA stratum-adjusted Mantel-Haenszel (MH) proportion.

2. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Description	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 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	Week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	E/C/F/TAF	E/C/F/TDF
Arm/Group Description	Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily
Measure Participants	112	58
Number [percentage of participants]	88.4 78.9%	87.9 151.6%

3. Secondary Outcome

Title	Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants in Full Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TAF	E/C/F/TDF
Arm/Group Description	Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily
Measure Participants	112	58
Baseline	4.63 (0.572)	4.69 (0.577)
Change at Week 24	-3.20 (0.654)	-3.26 (0.606)
Change at Week 48	-3.22 (0.606)	-3.33 (0.572)

4. Secondary Outcome

Title	Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Time Frame	Baseline; Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants in Full Analysis Set with available data were analyzed.

Arm/Group Title	E/C/F/TAF	E/C/F/TDF
Arm/Group Description	Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily	Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily
Measure Participants	112	58
Baseline	404 (181.6)	394 (209.6)
Change at Week 24	165 (115.6)	179 (127.7)
Change at Week 48	177 (144.1)	204 (120.4)

Adverse Events

Time Frame	Up to 186.2 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug. Double-blind phase (E/C/F/TAF and E/C/F/TDF arms): adverse events were coded using the Medical Dictionary for Regulated Activities (MedDRA), version 17.0 All E/C/F/TAF arm: adverse events were coded using MedDRA, version 19.0
Arm/Group Title	E/C/F/TAF		E/C/F/TDF		All E/C/F/TAF
Arm/Group Description	Adverse events in this reporting group include those that occurred during the double-blind phase by participants randomized to E/C/F/TAF. Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks; Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily		Adverse events in this reporting group include those that occurred during the double-blind phase by participants randomized to E/C/F/TDF. Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks; Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily		Adverse events in this reporting group include those that occurred any time during the study by participants while receiving E/C/F/TAF. Participants received blinded or open-label E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily
All Cause Mortality
	E/C/F/TAF		E/C/F/TDF		All E/C/F/TAF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	E/C/F/TAF		E/C/F/TDF		All E/C/F/TAF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/112 (10.7%)		3/58 (5.2%)		35/273 (12.8%)
Cardiac disorders
Acute myocardial infarction	1/112 (0.9%)		0/58 (0%)		2/273 (0.7%)
Cardiac failure acute	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Coronary artery disease	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Myocardial infarction	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Pericarditis	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Gastrointestinal disorders
Colitis	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Gastric ulcer haemorrhage	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Large intestine perforation	0/112 (0%)		1/58 (1.7%)		0/273 (0%)
Pancreatitis	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Small intestinal obstruction	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
General disorders
Non-cardiac chest pain	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Systemic inflammatory response syndrome	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Hepatobiliary disorders
Cholelithiasis	0/112 (0%)		0/58 (0%)		2/273 (0.7%)
Infections and infestations
Appendicitis	0/112 (0%)		0/58 (0%)		4/273 (1.5%)
Cellulitis	0/112 (0%)		0/58 (0%)		2/273 (0.7%)
Clostridium difficile colitis	0/112 (0%)		1/58 (1.7%)		0/273 (0%)
Coxsackie viral infection	1/112 (0.9%)		0/58 (0%)		0/273 (0%)
Cytomegalovirus colitis	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Erysipelas	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Furuncle	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Hepatitis C	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Infectious colitis	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Mycobacterium avium complex infection	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Neurosyphilis	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Perirectal abscess	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Pneumonia	1/112 (0.9%)		0/58 (0%)		2/273 (0.7%)
Pyelonephritis	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Sinusitis	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Upper respiratory tract infection	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Viral infection	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Viral rash	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Injury, poisoning and procedural complications
Ankle fracture	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Concussion	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Contusion	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Facial bones fracture	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Femur fracture	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Pelvic fracture	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Rib fracture	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Road traffic accident	0/112 (0%)		1/58 (1.7%)		0/273 (0%)
Subdural haematoma	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Thoracic vertebral fracture	0/112 (0%)		1/58 (1.7%)		0/273 (0%)
Upper limb fracture	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Intervertebral disc protrusion	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Lumbar spinal stenosis	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Pain in extremity	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute promyelocytic leukaemia	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Adenocarcinoma pancreas	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Malignant melanoma	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Nervous system disorders
Vertebral artery dissection	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Psychiatric disorders
Bipolar disorder	1/112 (0.9%)		0/58 (0%)		3/273 (1.1%)
Depression	1/112 (0.9%)		2/58 (3.4%)		3/273 (1.1%)
Drug abuse	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Psychotic disorder	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Suicidal ideation	1/112 (0.9%)		2/58 (3.4%)		2/273 (0.7%)
Renal and urinary disorders
Acute kidney injury	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Respiratory, thoracic and mediastinal disorders
Aspiration	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Dyspnoea	0/112 (0%)		0/58 (0%)		1/273 (0.4%)
Pleural effusion	1/112 (0.9%)		0/58 (0%)		1/273 (0.4%)
Pulmonary embolism	0/112 (0%)		1/58 (1.7%)		0/273 (0%)
Other (Not Including Serious) Adverse Events
	E/C/F/TAF		E/C/F/TDF		All E/C/F/TAF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/112 (81.3%)		48/58 (82.8%)		215/273 (78.8%)
Endocrine disorders
Hypogonadism	7/112 (6.3%)		0/58 (0%)		12/273 (4.4%)
Gastrointestinal disorders
Constipation	4/112 (3.6%)		3/58 (5.2%)		10/273 (3.7%)
Diarrhoea	19/112 (17%)		9/58 (15.5%)		40/273 (14.7%)
Dyspepsia	4/112 (3.6%)		3/58 (5.2%)		9/273 (3.3%)
Flatulence	6/112 (5.4%)		2/58 (3.4%)		6/273 (2.2%)
Nausea	25/112 (22.3%)		7/58 (12.1%)		35/273 (12.8%)
Toothache	3/112 (2.7%)		1/58 (1.7%)		15/273 (5.5%)
Vomiting	9/112 (8%)		4/58 (6.9%)		17/273 (6.2%)
General disorders
Fatigue	18/112 (16.1%)		5/58 (8.6%)		29/273 (10.6%)
Immune system disorders
Seasonal allergy	4/112 (3.6%)		3/58 (5.2%)		11/273 (4%)
Infections and infestations
Acarodermatitis	4/112 (3.6%)		3/58 (5.2%)		8/273 (2.9%)
Bronchitis	7/112 (6.3%)		3/58 (5.2%)		33/273 (12.1%)
Chlamydial infection	3/112 (2.7%)		2/58 (3.4%)		16/273 (5.9%)
Conjunctivitis	9/112 (8%)		0/58 (0%)		18/273 (6.6%)
Gastroenteritis	4/112 (3.6%)		2/58 (3.4%)		26/273 (9.5%)
Influenza	8/112 (7.1%)		0/58 (0%)		19/273 (7%)
Nasopharyngitis	7/112 (6.3%)		2/58 (3.4%)		31/273 (11.4%)
Pharyngitis	10/112 (8.9%)		2/58 (3.4%)		20/273 (7.3%)
Sinusitis	7/112 (6.3%)		3/58 (5.2%)		28/273 (10.3%)
Syphilis	5/112 (4.5%)		3/58 (5.2%)		38/273 (13.9%)
Upper respiratory tract infection	17/112 (15.2%)		12/58 (20.7%)		60/273 (22%)
Injury, poisoning and procedural complications
Procedural pain	3/112 (2.7%)		2/58 (3.4%)		14/273 (5.1%)
Metabolism and nutrition disorders
Hyperlipidaemia	3/112 (2.7%)		1/58 (1.7%)		19/273 (7%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/112 (4.5%)		2/58 (3.4%)		18/273 (6.6%)
Back pain	3/112 (2.7%)		8/58 (13.8%)		27/273 (9.9%)
Neck pain	3/112 (2.7%)		3/58 (5.2%)		4/273 (1.5%)
Osteopenia	4/112 (3.6%)		2/58 (3.4%)		14/273 (5.1%)
Pain in extremity	1/112 (0.9%)		3/58 (5.2%)		12/273 (4.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anorectal human papilloma virus infection	6/112 (5.4%)		4/58 (6.9%)		0/273 (0%)
Skin papilloma	0/112 (0%)		3/58 (5.2%)		4/273 (1.5%)
Nervous system disorders
Headache	11/112 (9.8%)		8/58 (13.8%)		26/273 (9.5%)
Paraesthesia	3/112 (2.7%)		4/58 (6.9%)		7/273 (2.6%)
Psychiatric disorders
Abnormal dreams	8/112 (7.1%)		1/58 (1.7%)		8/273 (2.9%)
Anxiety	4/112 (3.6%)		5/58 (8.6%)		15/273 (5.5%)
Depression	11/112 (9.8%)		2/58 (3.4%)		27/273 (9.9%)
Insomnia	6/112 (5.4%)		4/58 (6.9%)		14/273 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	11/112 (9.8%)		6/58 (10.3%)		36/273 (13.2%)
Oropharyngeal pain	4/112 (3.6%)		1/58 (1.7%)		14/273 (5.1%)
Skin and subcutaneous tissue disorders
Rash	11/112 (9.8%)		3/58 (5.2%)		22/273 (8.1%)

Limitations/Caveats

There were no limitations affecting the analysis or results.

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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