Trial Outcomes & Findings for Monitoring SOF/VEL in Treatment Naïve, HCV Participants With Active Infection (NCT NCT03512210)

NCT ID: NCT03512210

Last Updated: 2022-02-04

Results Overview

SVR12 was defined as plasma HCV RNA less than the lower limit of quantification (LLOQ) from the earliest sample drawn at least 22 weeks following study treatment initiation (i.e. at a visit scheduled at least 10 weeks after scheduled end of study treatment). Participants without any HCV RNA result at least 22 weeks after treatment initiation will be considered as having HCV RNA greater than the LLOQ. LLOQ was defined as \<15 IU/mL for results tested at USA centralized testing laboratory Quest using the "Roche COBAS® HCV Quantitative nucleic acid test for use on the COBAS® 6800/8800" assays for quantitation (and detection) of HCV, and \<12 IU/mL for results tested at regional international labs using "Abbott RealTime HCV" assay for quantitation (and detection) of HCV. A two-sided 95%, confidence interval was calculated for this percentage using the Wilson (score) method.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 400 participants
• Primary outcome timeframe: From at least 22 weeks and up to 76 weeks from treatment initiation
• Results posted on: 2022-02-04

Participant Flow

Participants were enrolled from October 2018 to July 2019 at 38 sites in Brazil, South Africa, Thailand, Uganda, and the United States.

There was no randomization in this study. Enrollment from sites located in the United States was restricted to 132 participants. Enrollment of participants having compensated cirrhosis was limited to no more than 80 participants, and enrollment of people living with HIV was limited to no more than 200 participants.

Participant milestones

Measure	MINMON 24 Weeks With SOF/VEL 12 Weeks Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22
Step 1: MINMON Intervention STARTED	400
Step 1: MINMON Intervention COMPLETED	396
Step 1: MINMON Intervention NOT COMPLETED	4
Step 2:Post-MINMON STARTED	396
Step 2:Post-MINMON COMPLETED	362
Step 2:Post-MINMON NOT COMPLETED	34

Reasons for withdrawal

Measure	MINMON 24 Weeks With SOF/VEL 12 Weeks Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22
Step 1: MINMON Intervention Lost to Follow-up	3
Step 1: MINMON Intervention Protocol Violation	1
Step 2:Post-MINMON Death	2
Step 2:Post-MINMON Lost to Follow-up	30
Step 2:Post-MINMON Withdrawal by Subject	2

Baseline Characteristics

Monitoring SOF/VEL in Treatment Naïve, HCV Participants With Active Infection

Baseline characteristics by cohort

Measure	MINMON 24 Weeks With SOF/VEL 12 Weeks n=399 Participants Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22
Age, Continuous	47 years n=5 Participants
Age, Customized 20 to 29 years	33 Participants n=5 Participants
Age, Customized 30 to 39 years	95 Participants n=5 Participants
Age, Customized 40 to 49 years	100 Participants n=5 Participants
Age, Customized 50 to 59 years	97 Participants n=5 Participants
Age, Customized 60 to 69 years	55 Participants n=5 Participants
Age, Customized 70 to 79 years	18 Participants n=5 Participants
Age, Customized 80+ years	1 Participants n=5 Participants
Sex: Female, Male Female	139 Participants n=5 Participants
Sex: Female, Male Male	260 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	95 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	289 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	113 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	72 Participants n=5 Participants
Race (NIH/OMB) White	166 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	47 Participants n=5 Participants
Region of Enrollment Brazil	131 participants n=5 Participants
Region of Enrollment South Africa	12 participants n=5 Participants
Region of Enrollment Thailand	110 participants n=5 Participants
Region of Enrollment Uganda	15 participants n=5 Participants
Region of Enrollment United States	131 participants n=5 Participants
Gender Identity Cisgender	377 Participants n=5 Participants
Gender Identity Transgender Spectrum	22 Participants n=5 Participants
HIV-infection Status HIV-1 infection absent	233 Participants n=5 Participants
HIV-infection Status HIV-1 infection present	166 Participants n=5 Participants
Cirrhosis Status Cirrhosis present	34 Participants n=5 Participants
Cirrhosis Status Cirrhosis absent	365 Participants n=5 Participants
HCV RNA	6.1 Log10 IU/ml n=5 Participants
HCV Genotype Genotype 1	249 Participants n=5 Participants
HCV Genotype Genotype 2	26 Participants n=5 Participants
HCV Genotype Genotype 3	80 Participants n=5 Participants
HCV Genotype Genotype 4	26 Participants n=5 Participants
HCV Genotype Genotype 5	3 Participants n=5 Participants
HCV Genotype Genotype 6	11 Participants n=5 Participants
HCV Genotype Genotype 7	1 Participants n=5 Participants
HCV Genotype Unknown Genotype	3 Participants n=5 Participants
Self Reported History of Substance Use Currently	56 Participants n=5 Participants
Self Reported History of Substance Use Previously	170 Participants n=5 Participants
Self Reported History of Substance Use Never	171 Participants n=5 Participants
Self Reported History of Substance Use Not evaluated	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From at least 22 weeks and up to 76 weeks from treatment initiation

Population: Participants who enrolled and received first dose of study medication.

SVR12 was defined as plasma HCV RNA less than the lower limit of quantification (LLOQ) from the earliest sample drawn at least 22 weeks following study treatment initiation (i.e. at a visit scheduled at least 10 weeks after scheduled end of study treatment). Participants without any HCV RNA result at least 22 weeks after treatment initiation will be considered as having HCV RNA greater than the LLOQ.

LLOQ was defined as <15 IU/mL for results tested at USA centralized testing laboratory Quest using the "Roche COBAS® HCV Quantitative nucleic acid test for use on the COBAS® 6800/8800" assays for quantitation (and detection) of HCV, and <12 IU/mL for results tested at regional international labs using "Abbott RealTime HCV" assay for quantitation (and detection) of HCV.

A two-sided 95%, confidence interval was calculated for this percentage using the Wilson (score) method.

Outcome measures

Measure

MINMON 24 Weeks With SOF/VEL 12 Weeks n=399 Participants Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22

Percentage of Participants With Sustained Virologic Response 12 (SVR12)

95.0 percentage of participants Interval 92.4 to 96.7

PRIMARY outcome

Timeframe: From treatment initiation to 28 weeks

Population: Participants who received first dose of study medication and had at least one post-entry evaluation for adverse events.

Serious adverse events (SAEs) as defined by ICH guidelines.

A two-sided, 95% confidence interval was calculated for the percentage using the Wilson (score) method.

Outcome measures

Measure

MINMON 24 Weeks With SOF/VEL 12 Weeks n=397 Participants Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22

Percentage of Participants With an Occurrence of Serious Adverse Events According to International Council for Harmonization (ICH) Criteria

3.5 percentage of participants Interval 2.1 to 5.8

SECONDARY outcome

Timeframe: From treatment initiation to 22 weeks

Population: Participants who enrolled and received first dose of study medication.

According to the study minimal monitoring intervention, there were no planned clinic visits prior to study week 24, when SVR12 was scheduled to be evaluated. An unplanned clinic visit was defined as an in-clinic visit occurring from treatment initiation to up to week 22.

A two-sided, 95% confidence interval was calculated for the percentage using the Wilson (score) method.

Outcome measures

Measure

MINMON 24 Weeks With SOF/VEL 12 Weeks n=399 Participants Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22

Percentage of Participants With at Least One Unplanned Clinic Visit Prior to SVR12 Evaluation

3.8 percentage of participants Interval 2.3 to 6.1

SECONDARY outcome

Timeframe: From treatment initiation to 28 weeks

Population: Participants who received first dose of study medication and had at least one post-entry evaluation for adverse events.

AEs included all primary diagnoses, primary signs/symptoms, and primary laboratory abnormalities that either had severity grade ≥ 3 or led to a change in study medication. Serious Adverse Events (SAE) by International Council for Harmonization (ICH) criteria were excluded as they contributed to the primary safety outcome measure.

Severity grading was based on DAIDS AE Grading Table, Corrected Version 2.1.

A two-sided, 95% confidence interval was calculated for the percentage using the Wilson (score) method.

Outcome measures

Measure

MINMON 24 Weeks With SOF/VEL 12 Weeks n=397 Participants Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22

Percentage of Participants With an Occurrence of One or More Non-serious, Grade >= 3 Adverse Event (AE), or Treatment Limiting AE.

5.8 percentage of participants Interval 5.1 to 6.6

SECONDARY outcome

Timeframe: From at least 22 weeks and up to 76 weeks from treatment initiation

Population: Participants who enrolled into study and received first dose of study medication.

Since there were no planned clinic visits during the 12 week study medication period, the last dose of study treatment was self-reported by participants, and recorded at the SVR evaluation visit at 24 weeks. Premature treatment discontinuation was defined when the self-reported final dose date was <11 weeks (<77 days) after the date of initial dose (accounting for any reported treatment holds). Participants discontinuing study follow up without information about completion of HCV study medications were counted as having prematurely discontinued medications.

A two-sided, 95% confidence interval was calculated for the percentage using the Wilson (score) method.

Outcome measures

Measure

MINMON 24 Weeks With SOF/VEL 12 Weeks n=399 Participants Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22

Percentage of Participants Who Prematurely Discontinued HCV Study Medications

1.0 percentage of participants Interval 0.4 to 2.5

Adverse Events

MINMON 24 Weeks With SOF/VEL 12 Weeks

Serious events: 31 serious events

Other events: 58 other events

Deaths: 2 deaths

Serious adverse events

Measure	MINMON 24 Weeks With SOF/VEL 12 Weeks n=397 participants at risk Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22
Blood and lymphatic system disorders Anaemia	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Cardiac disorders Acute myocardial infarction	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Cardiac disorders Acute right ventricular failure	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Cardiac disorders Ischaemic cardiomyopathy	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Diverticular perforation	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Dyspepsia	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Infections and infestations Pneumonia	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Infections and infestations Urinary tract infection	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Accidental overdose	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Femur fracture	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Intentional overdose	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Overdose	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Spinal fracture	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Haemoglobin decreased	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Ischaemic stroke	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Neuromyelitis optica spectrum disorder	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Seizure	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Depression	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Intentional self-injury	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Major depression	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Persistent depressive disorder	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Psychotic disorder	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Schizoaffective disorder depressive type	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Suicidal ideation	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Renal and urinary disorders Acute kidney injury	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Renal and urinary disorders Ureterolithiasis	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Social circumstances Substance use	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Vascular disorders Hypertension	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.

Other adverse events

Measure	MINMON 24 Weeks With SOF/VEL 12 Weeks n=397 participants at risk Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks Sofosbuvir/Velpatasvir (SOF/VEL): 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. Minimal Monitoring (MINMON) Strategy: MINMON Strategy: 1. No pre-treatment HCV genotyping 2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry 3. No scheduled on-treatment laboratory monitoring or clinic visits 4. Remote contact with participants at week 4 and week 22
Blood and lymphatic system disorders Thrombocytopenia	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Cardiac disorders Acute left ventricular failure	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Cardiac disorders Left ventricular failure	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Congenital, familial and genetic disorders Gilbert's syndrome	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Eye disorders Chorioretinopathy	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Eye disorders Retinal detachment	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Abdominal distension	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Abdominal pain	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Constipation	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Diarrhoea	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Gastrointestinal disorders Glossodynia	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
General disorders Fatigue	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
General disorders Pyrexia	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Infections and infestations Upper respiratory tract infection	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Ankle fracture	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Humerus fracture	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Injury, poisoning and procedural complications Spinal fracture	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Alanine aminotransferase increased	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Aspartate aminotransferase increased	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Blood bilirubin increased	0.76% 3/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Blood creatinine increased	1.3% 5/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Blood pressure increased	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Creatinine renal clearance decreased	5.5% 22/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Haemoglobin decreased	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Investigations Weight decreased	0.76% 3/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Metabolism and nutrition disorders Abnormal loss of weight	1.3% 5/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Metabolism and nutrition disorders Hyperglycaemia	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Musculoskeletal and connective tissue disorders Back pain	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Musculoskeletal and connective tissue disorders Muscular weakness	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Musculoskeletal and connective tissue disorders Neck pain	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Musculoskeletal and connective tissue disorders Pain in extremity	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Headache	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Hypoaesthesia	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Anxiety	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Depressive symptom	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Hallucination	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Psychiatric disorders Suicidal ideation	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Renal and urinary disorders Dysuria	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Renal and urinary disorders Urine abnormality	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Acute lung injury	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.50% 2/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Vascular disorders Hypertension	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.
Vascular disorders Hypertensive urgency	0.25% 1/397 • From treatment initiation to study completion at week 72. The week 72 window was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites in response to COVID-19, up to a maximum of 110 weeks. For participants who received first dose of SOF/VEL and had at least one post-entry evaluation for AEs. Post-entry, all signs/symptoms, diagnoses, or abnormal laboratory findings new in onset or aggravated in severity or frequency from the baseline condition and meeting any of the following criteria were reported: ≥ Grade 3, led to change in SOF/VEL regardless of grade, or met expedited AE or ICH SAE guidelines. The DAIDS AE Grading Table (Correct V2.1) and Expedited AE Manual (V2.0) were used.

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

Phone: 301-628-3348

Email: ACTGCT.gov@fstrf.org

Results disclosure agreements

• Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER