Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02073656
• Collaborator: (none)
• Enrollment: 335
• Locations: 41
• Arms: 2
• Duration (Months): 21.9
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) administered for 12 weeks in hepatitis C virus (HCV) treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic genotype 1 or 4 HCV infection who are co-infected with HIV-1.

Participants who experience confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 may be eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF plus ribavirin (RBV) for 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus; HIV	Drug: LDV/SOF; Drug: RBV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 335 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Co-infection
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDV/SOF 12 Weeks LDV/SOF for 12 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977
Experimental: Retreatment Substudy LDV/SOF plus RBV for 24 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977 ; Drug: RBV; Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.

2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [Up to 12 weeks]

Secondary Outcome Measures

1. Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [Posttreatment Weeks 4 and 24]

   SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.

2. Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 [Weeks 1, 2, 4, 6, 8, 10, and 12]

3. Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8 [Baseline; Weeks 1, 2, 4, 6, and 8]

4. Percentage of Participants With Virologic Failure [Up to Posttreatment Week 24]

   Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

5. Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment [Weeks 4, 8, and 12]

6. Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24 [Baseline; Week 12, Posttreatment Weeks 12 and 24]

7. For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) [Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy]

   SVR4, SVR12, and SVR 24 were defined as HCV RNA < LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.

8. For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24 [Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy]

9. For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8 [Baseline; Weeks 2, 4, and 8 of Retreatment Substudy]

10. For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure [Up to Posttreatment Week 24 of Retreatment Substudy]

    Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• HCV RNA ≥ 10,000 IU/mL at screening

• HCV genotype 1 or 4

• HIV-1 infection

• Cirrhosis determination, a fibroscan or liver biopsy may be required

• Screening laboratory values within defined thresholds

• Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion Criteria:

• Clinically-significant illness (other than HCV or HIV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol

• Current or prior history of clinical hepatic decompensation, hepatocellular carcinoma (HCC), or other malignancy (with the exception of certain resolved skin cancers)

• Hepatitis B virus (HBV) infection

• Pregnant or nursing female

• Chronic use of systemically administered immunosuppressive agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35294-2170
2		Los Angeles	California	United States	90027
3		Newport Beach	California	United States	92663
4		Palo Alto	California	United States	94304-5350
5		Sacramento	California	United States	95817
6		San Diego	California	United States	92103
7		San Francisco	California	United States	94110
8		Torrance	California	United States	90502
9		Denver	Colorado	United States	80209
10		Washington	District of Columbia	United States	20815
11		Bradenton	Florida	United States	34209
12		Miami	Florida	United States	33136
13		Orlando	Florida	United States	32803
14		Tampa	Florida	United States	33614
15		Atlanta	Georgia	United States	30312
16		Decatur	Georgia	United States	30033
17		Chicago	Illinois	United States	60612
18		Lutherville	Maryland	United States	21093
19		Boston	Massachusetts	United States	02115
20		Kansas City	Missouri	United States	64111
21		Santa Fe	New Mexico	United States	87505
22		Bronx	New York	United States	10468
23		New York	New York	United States	10065
24		Chapel Hill	North Carolina	United States	27599
25		Durham	North Carolina	United States	27710
26		Cincinnati	Ohio	United States	45267-0595
27		Allentown	Pennsylvania	United States	18102
28		Philadelphia	Pennsylvania	United States	19107
29		Providence	Rhode Island	United States	02906
30		Dallas	Texas	United States	75235
31		Houston	Texas	United States	77004
32		Annandale	Virginia	United States	22003
33		Richmond	Virginia	United States	23298-0341
34		Seattle	Washington	United States	98104
35		Vancouver	British Columbia	Canada	V6Z 1Y6
36		Ottawa	Ontario	Canada	K1H 8L6
37		Toronto	Ontario	Canada	M5G 2N2
38		Montreal	Quebec	Canada	H2L 5B1
39		Auckland		New Zealand	1142
40		Christchurch		New Zealand	8011
41		San Juan		Puerto Rico	00936-5607

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Jenny Yang, PharmD, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02073656
• Other Study ID Numbers: GS-US-337-0115
• First Posted: Feb 27, 2014
• Last Update Posted: Nov 16, 2018
• Last Verified: Aug 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Gilead Sciences: genotype 1; genotype 4; HIV
• Additional relevant MeSH terms: Hepatitis C; Coinfection; Hepatitis; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in the United States (including Puerto Rico), Canada, and New Zealand. The first participant was screened on 24 February 2014. The last study visit occurred on 01 December 2015.
Pre-assignment Detail	429 participants were screened.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for up to 12 weeks. Participants who experienced confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 were eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF (90/400 mg) FDC tablet once daily + ribavirin (RBV) tablets (1000-1200 mg daily based on weight) for 24 weeks.
Period Title: Primary Study
STARTED	335
COMPLETED	327
NOT COMPLETED	8
Period Title: Primary Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for up to 12 weeks.
Overall Participants	335
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (8.0)
Sex: Female, Male (Count of Participants)
Female	59 17.6%
Male	276 82.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	56 16.7%
Not Hispanic or Latino	276 82.4%
Unknown or Not Reported	3 0.9%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	115 34.3%
White	203 60.6%
Asian	6 1.8%
American Indian/ Alaska Native	2 0.6%
Other	6 1.8%
Not Disclosed	3 0.9%
Region of Enrollment (participants) [Number]
New Zealand	9 2.7%
Canada	26 7.8%
United States	290 86.6%
Puerto Rico	10 3%
HCV Genotype (participants) [Number]
Genotype 1a	250 74.6%
Genotype 1b	77 23%
Genotype 4	8 2.4%
Cirrhosis Status (participants) [Number]
No	268 80%
Yes	67 20%
IL28b Status (participants) [Number]
CC	81 24.2%
CT	185 55.2%
TT	69 20.6%
Baseline HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.7 (0.64)
Baseline HCV RNA Category (participants) [Number]
< 800,000 IU/mL	36 10.7%
≥ 800,000 IU/mL	299 89.3%
Baseline Serum Creatinine (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.00 (0.210)
Estimated Glomerular Filtration Rate Using the Cockcroft-Gault Equation (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	101.6 (30.78)
Baseline CD4 Count (cells/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/uL]	662 (293.8)
Prior HCV Treatment (participants) [Number]
Treatment-Naive	150 44.8%
Treatment-Experienced with DAA+Peg-IFN+RBV	53 15.8%
Treatment-Experienced with Peg-IFN+RBV	113 33.7%
Treatment-Experienced with DAA+RBV	14 4.2%
Treatment-Experienced with Other	5 1.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who enrolled and received at least 1 dose of study drug.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
Number (95% Confidence Interval) [percentage of participants]	96.1 28.7%

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who enrolled and received at least 1 dose of study drug.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
Number [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description	SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Time Frame	Posttreatment Weeks 4 and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
SVR4	96.7 28.9%
SVR24	96.1 28.7%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12
Time Frame	Weeks 1, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
Week 1 (N = 335)	29.3 8.7%
Week 2 (N = 335)	81.2 24.2%
Week 4 (N = 335)	98.8 29.5%
Week 6 (N = 335)	99.1 29.6%
Week 8 (N = 334)	99.4 29.7%
Week 10 (N = 332)	100.0 29.9%
Week 12 (N = 332)	100.0 29.9%

5. Secondary Outcome

Title	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8
Time Frame	Baseline; Weeks 1, 2, 4, 6, and 8

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
Change at Week 1 (N = 331)	-4.68 (0.674)
Change at Week 2 (N = 334)	-5.21 (0.654)
Change at Week 4 (N = 335)	-5.30 (0.743)
Change at Week 6 (N = 334)	-5.30 (0.772)
Change at Week 8 (N = 333)	-5.33 (0.645)

6. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
On-Treatment Virologic Failure (N = 335)	0.6 0.2%
Virologic Relapse (N = 333)	3.0 0.9%

7. Secondary Outcome

Title	Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment
Time Frame	Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
Week 4 (N = 335)	98.5 29.4%
Week 8 (N = 334)	98.2 29.3%
Week 12 (N = 334)	97.9 29.2%

8. Secondary Outcome

Title	Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24
Time Frame	Baseline; Week 12, Posttreatment Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	LDV/SOF 12 Weeks
Arm/Group Description	Primary Study: LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.
Measure Participants	335
Change at Week 12 (N = 320)	0.05 (0.111)
Change at Posttreatment Week 12 (N = 325)	0.03 (0.143)
Change at Posttreatment Week 24 (N = 313)	-0.02 (0.134)

9. Secondary Outcome

Title	For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24)
Description	SVR4, SVR12, and SVR 24 were defined as HCV RNA < LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.
Time Frame	Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set who entered the Retreatment Substudy were analyzed.

Arm/Group Title	LDV/SOF+RBV 24 Weeks (Retreatment Substudy)
Arm/Group Description	Participants who experienced confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 during the Primary Study were eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks.
Measure Participants	9
SVR4	88.9 26.5%
SVR12	88.9 26.5%
SVR24	88.9 26.5%

10. Secondary Outcome

Title	For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24
Time Frame	Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set who entered the Retreatment Substudy were analyzed.

Arm/Group Title	LDV/SOF+RBV 24 Weeks (Retreatment Substudy)
Arm/Group Description	Participants who experienced confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 during the Primary Study were eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks.
Measure Participants	9
Week 2 Retreatment	88.9 26.5%
Week 4 Retreatment	100.0 29.9%
Week 8 Retreatment	100.0 29.9%
Week 12 Retreatment	100.0 29.9%
Week 16 Retreatment	100.0 29.9%
Week 20 Retreatment	100.0 29.9%
Week 24 Retreatment	100.0 29.9%

11. Secondary Outcome

Title	For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8
Time Frame	Baseline; Weeks 2, 4, and 8 of Retreatment Substudy

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set who entered the Retreatment Substudy were analyzed.

Arm/Group Title	LDV/SOF+RBV 24 Weeks (Retreatment Substudy)
Arm/Group Description	Participants who experienced confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 during the Primary Study were eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks.
Measure Participants	9
Change at Week 2 Retreatment	-5.01 (0.775)
Change at Week 4 Retreatment	-5.04 (0.802)
Change at Week 8 Retreatment	-5.04 (0.802)

12. Secondary Outcome

Title	For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure
Description	Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Time Frame	Up to Posttreatment Week 24 of Retreatment Substudy

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set who entered the Retreatment Substudy were analyzed.

Arm/Group Title	LDV/SOF+RBV 24 Weeks (Retreatment Substudy)
Arm/Group Description	Participants who experienced confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 during the Primary Study were eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks.
Measure Participants	9
On-Treatment Virologic Failure	0 0%
Virologic Relapse	11.1 3.3%

Adverse Events

Time Frame	LDV/SOF 12 Weeks: Up to 12 weeks plus 30 days; LDV/SOF+RBV 24 Weeks: Up to 24 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	LDV/SOF 12 Weeks (Primary Study)		LDV/SOF+RBV 24 Weeks (Retreatment)
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet once daily for up to 12 weeks.		Participants who experienced confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 during the Primary Study were eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF (90/400 mg) FDC tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for 24 weeks.
All Cause Mortality
	LDV/SOF 12 Weeks (Primary Study)		LDV/SOF+RBV 24 Weeks (Retreatment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LDV/SOF 12 Weeks (Primary Study)		LDV/SOF+RBV 24 Weeks (Retreatment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/335 (2.4%)		0/9 (0%)
Gastrointestinal disorders
Diarrhoea	1/335 (0.3%)		0/9 (0%)
Ileus	1/335 (0.3%)		0/9 (0%)
Hepatobiliary disorders
Portal vein thrombosis	2/335 (0.6%)		0/9 (0%)
Infections and infestations
Clostridium difficile colitis	1/335 (0.3%)		0/9 (0%)
Peritonitis bacterial	1/335 (0.3%)		0/9 (0%)
Respiratory tract infection	1/335 (0.3%)		0/9 (0%)
Sepsis	1/335 (0.3%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/335 (0.3%)		0/9 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	2/335 (0.6%)		0/9 (0%)
Psychiatric disorders
Substance abuse	1/335 (0.3%)		0/9 (0%)
Renal and urinary disorders
Azotaemia	1/335 (0.3%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/335 (0.3%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	LDV/SOF 12 Weeks (Primary Study)		LDV/SOF+RBV 24 Weeks (Retreatment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	179/335 (53.4%)		9/9 (100%)
Blood and lymphatic system disorders
Anaemia	2/335 (0.6%)		3/9 (33.3%)
Haemolytic anaemia	0/335 (0%)		1/9 (11.1%)
Eye disorders
Vision blurred	2/335 (0.6%)		1/9 (11.1%)
Gastrointestinal disorders
Diarrhoea	35/335 (10.4%)		1/9 (11.1%)
Nausea	33/335 (9.9%)		1/9 (11.1%)
Vomiting	14/335 (4.2%)		1/9 (11.1%)
General disorders
Fatigue	71/335 (21.2%)		6/9 (66.7%)
Chest discomfort	0/335 (0%)		1/9 (11.1%)
Cyst	0/335 (0%)		1/9 (11.1%)
Infections and infestations
Upper respiratory tract infection	18/335 (5.4%)		1/9 (11.1%)
Acute sinusitis	0/335 (0%)		1/9 (11.1%)
Investigations
Blood uric acid increased	0/335 (0%)		1/9 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	8/335 (2.4%)		1/9 (11.1%)
Increased appetite	1/335 (0.3%)		1/9 (11.1%)
Abnormal loss of weight	0/335 (0%)		1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	23/335 (6.9%)		2/9 (22.2%)
Back pain	7/335 (2.1%)		1/9 (11.1%)
Musculoskeletal pain	3/335 (0.9%)		1/9 (11.1%)
Foot deformity	0/335 (0%)		1/9 (11.1%)
Nervous system disorders
Headache	82/335 (24.5%)		1/9 (11.1%)
Dizziness	11/335 (3.3%)		1/9 (11.1%)
Psychiatric disorders
Irritability	10/335 (3%)		1/9 (11.1%)
Emotional disorder	0/335 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	8/335 (2.4%)		4/9 (44.4%)
Upper-airway cough syndrome	1/335 (0.3%)		1/9 (11.1%)
Dysphonia	0/335 (0%)		1/9 (11.1%)
Nasal dryness	0/335 (0%)		1/9 (11.1%)
Skin and subcutaneous tissue disorders
Rash	4/335 (1.2%)		1/9 (11.1%)
Dry skin	2/335 (0.6%)		1/9 (11.1%)
Ingrowing nail	1/335 (0.3%)		1/9 (11.1%)
Rash generalised	0/335 (0%)		1/9 (11.1%)

Limitations/Caveats

[Not Specified]

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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