Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment (NCT NCT02707601)

Last Updated: 2018-11-14

Results Overview

Sustained Virologic Response (SVR12) was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

150 participants

Primary outcome timeframe

HCV Posttreatment Week 12

Results posted on

2018-11-14

Participant Flow

Participants were enrolled at study sites in the United States. The first participant was screened on 01 April 2016. The last study visit occurred on 29 September 2017.

259 participants were screened.

Participant milestones

Participant milestones
Measure	E/C/F/TAF + LDV/SOF Part 1: Participants received elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF Part 1: Participants received emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Overall Study STARTED	76	74
Overall Study COMPLETED	72	70
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	E/C/F/TAF + LDV/SOF Part 1: Participants received elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF Part 1: Participants received emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Overall Study Death	0	1
Overall Study Lack of Efficacy	0	1
Overall Study Investigator's Discretion	1	0
Overall Study Withdrew Consent	0	1
Overall Study Lost to Follow-up	1	1
Overall Study Participants Randomized but Not Treated	2	0

Baseline Characteristics

Efficacy, Safety, and Tolerability of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Participants Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	E/C/F/TAF + LDV/SOF n=74 Participants Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=74 Participants Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	Total n=148 Participants Total of all reporting groups
Age, Continuous	51 years STANDARD_DEVIATION 9.5 • n=5 Participants	52 years STANDARD_DEVIATION 9.9 • n=7 Participants	51 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	52 Participants n=7 Participants	110 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=5 Participants	59 Participants n=7 Participants	120 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized White	41 Participants n=5 Participants	37 Participants n=7 Participants	78 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
HCV RNA Category < 800,000 IU/mL	25 Participants n=5 Participants	14 Participants n=7 Participants	39 Participants n=5 Participants
HCV RNA Category ≥ 800,000 IU/mL	49 Participants n=5 Participants	60 Participants n=7 Participants	109 Participants n=5 Participants
HIV-1 RNA Category < 50 copies/mL	73 Participants n=5 Participants	74 Participants n=7 Participants	147 Participants n=5 Participants
HIV-1 RNA Category ≥ 50 copies/mL	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
HCV RNA	6.0 log10 IU/mL STANDARD_DEVIATION 1.07 • n=5 Participants	6.3 log10 IU/mL STANDARD_DEVIATION 0.74 • n=7 Participants	6.2 log10 IU/mL STANDARD_DEVIATION 0.92 • n=5 Participants

PRIMARY outcome

Timeframe: HCV Posttreatment Week 12

Population: HCV Full Analysis Set: participants who were randomized into the study and received at least 1 dose of HCV study drug, LDV/SOF.

Sustained Virologic Response (SVR12) was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.

Outcome measures

Outcome measures
Measure	E/C/F/TAF + LDV/SOF n=72 Participants Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=72 Participants Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	E/C/F/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV Week 12) Part 1: Participants received E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV to Week 12) Part 1: Participants received F/R/TAF 200/25/25 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving (F/R/TAF) 200/25/25 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)	98.6 percentage of participants Interval 92.5 to 100.0	95.8 percentage of participants Interval 88.3 to 99.1	—	—

SECONDARY outcome

Timeframe: HCV Posttreatment Week 4

Population: HCV Full Analysis Set

SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping LDV/SOF treatment.

Outcome measures

Outcome measures
Measure	E/C/F/TAF + LDV/SOF n=72 Participants Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=72 Participants Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	E/C/F/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV Week 12) Part 1: Participants received E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV to Week 12) Part 1: Participants received F/R/TAF 200/25/25 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving (F/R/TAF) 200/25/25 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)	98.6 percentage of participants Interval 92.5 to 100.0	98.6 percentage of participants Interval 92.5 to 100.0	—	—

SECONDARY outcome

Timeframe: 24 weeks after start of HIV treatment

Population: HIV Full Analysis Set: participants who were randomized into the study and received at least 1 dose of HIV study drug, E/C/F/TAF or F/R/TAF.

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Outcome measures

Outcome measures
Measure	E/C/F/TAF + LDV/SOF n=74 Participants Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=74 Participants Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	E/C/F/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV Week 12) Part 1: Participants received E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV to Week 12) Part 1: Participants received F/R/TAF 200/25/25 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving (F/R/TAF) 200/25/25 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm	1.4 percentage of participants	1.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Up to 32 weeks plus 30 days

Population: Safety Analysis Set (Whole Study): participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF). Safety Analysis Set (Part 2): participants who entered Part 2 of the study and received at least one dose of study drug LDV/SOF.

Outcome measures

Outcome measures
Measure	E/C/F/TAF + LDV/SOF n=72 Participants Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=72 Participants Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	E/C/F/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV Week 12) n=74 Participants Part 1: Participants received E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF (Whole Study: Day 1 to Post-HCV to Week 12) n=74 Participants Part 1: Participants received F/R/TAF 200/25/25 mg tablet orally once daily with food for 8 weeks. Part 2: Participants continued receiving (F/R/TAF) 200/25/25 mg tablet orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment	62.5 percentage of participants	69.4 percentage of participants	83.8 percentage of participants	79.7 percentage of participants

Adverse Events

E/C/F/TAF + LDV/SOF

Serious events: 7 serious events

Other events: 46 other events

Deaths: 0 deaths

F/R/TAF + LDV/SOF

Serious events: 12 serious events

Other events: 36 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER

Measure	E/C/F/TAF + LDV/SOF n=74 participants at risk Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=74 participants at risk Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Blood and lymphatic system disorders Iron deficiency anaemia	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Gastrointestinal disorders Abdominal pain	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
General disorders Asthenia	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
General disorders Chest pain	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Gastroenteritis	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Influenza	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Pneumonia	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	2.7% 2/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Testicular abscess	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Tooth infection	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Investigations Blood pressure orthostatic abnormal	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Metabolism and nutrition disorders Dehydration	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of unknown primary site	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Nervous system disorders Headache	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Nervous system disorders Syncope	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Psychiatric disorders Confusional state	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Psychiatric disorders Depression	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Psychiatric disorders Suicidal ideation	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Psychiatric disorders Suicide attempt	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Renal and urinary disorders Acute kidney injury	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Skin and subcutaneous tissue disorders Angioedema	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).

Measure	E/C/F/TAF + LDV/SOF n=74 participants at risk Part 1: Participants received E/C/F/TAF 150/150/200/10 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to E/C/F/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving E/C/F/TAF 150/150/200/10 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).	F/R/TAF + LDV/SOF n=74 participants at risk Part 1: Participants received F/R/TAF 200/25/25 mg orally once daily with food for 8 weeks. At Week 8, participants who tolerated the switch to F/R/TAF and maintained HIV-1 RNA \< 50 copies/mL continued to Part 2 of the study. Part 2: Participants continued receiving F/R/TAF 200/25/25 mg orally once daily with food until the end of the study and received LDV/SOF 90/400 mg orally once daily with or without food for 12 weeks (until Week 20).
Gastrointestinal disorders Abdominal pain	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	4.1% 3/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Gastrointestinal disorders Diarrhoea	8.1% 6/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	4.1% 3/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Gastrointestinal disorders Nausea	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	8.1% 6/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
General disorders Fatigue	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	6.8% 5/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
General disorders Influenza like illness	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Bronchitis	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Upper respiratory tract infection	12.2% 9/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	6.8% 5/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Infections and infestations Urinary tract infection	13.5% 10/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	2.7% 2/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Metabolism and nutrition disorders Vitamin D deficiency	6.8% 5/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	2.7% 2/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 7/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	6.8% 5/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Musculoskeletal and connective tissue disorders Back pain	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	2.7% 2/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.4% 4/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Musculoskeletal and connective tissue disorders Pain in extremity	8.1% 6/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	1.4% 1/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Nervous system disorders Headache	4.1% 3/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	10.8% 8/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Respiratory, thoracic and mediastinal disorders Cough	8.1% 6/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	13.5% 10/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).
Vascular disorders Hypertension	0.00% 0/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).	6.8% 5/74 • Up to 32 weeks plus 30 days Safety Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug (E/C/F/TAF, F/R/TAF, or LDV/SOF).