Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With Other Antiretroviral Agents in People Living With HIV (NCT NCT04143594)

Last Updated: 2024-10-02

Results Overview

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 54 was 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. Week 54 window was between Day 323 and 413 (inclusive). Percentages were rounded off.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

183 participants

Primary outcome timeframe

Week 54

Results posted on

2024-10-02

Participant Flow

Participants were enrolled at study sites in Dominican Republic, Puerto Rico, and the United States.

249 participants were screened.

Participant milestones

Participant milestones
Measure	Group 1: SC LEN+(F/TAF→ TAF) Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Overall Study STARTED	52	53	52	26
Overall Study COMPLETED	41	35	36	24
Overall Study NOT COMPLETED	11	18	16	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: SC LEN+(F/TAF→ TAF) Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Overall Study Withdrew consent	3	10	3	1
Overall Study Lost to Follow-up	3	5	11	0
Overall Study Investigator's discretion	2	2	0	0
Overall Study Randomized but never treated	0	0	0	1
Overall Study Death	1	0	1	0
Overall Study Adverse Event	1	0	0	0
Overall Study Pregnancy	0	0	1	0
Overall Study Lack of Efficacy	1	1	0	0

Baseline Characteristics

Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With Other Antiretroviral Agents in People Living With HIV

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.	Total n=182 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	52 Participants n=5 Participants	53 Participants n=7 Participants	51 Participants n=5 Participants	25 Participants n=4 Participants	181 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Continuous	33 years STANDARD_DEVIATION 9.5 • n=5 Participants	30 years STANDARD_DEVIATION 8.8 • n=7 Participants	32 years STANDARD_DEVIATION 12.3 • n=5 Participants	33 years STANDARD_DEVIATION 11.1 • n=4 Participants	32 years STANDARD_DEVIATION 10.4 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	0 Participants n=4 Participants	12 Participants n=21 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	52 Participants n=7 Participants	46 Participants n=5 Participants	25 Participants n=4 Participants	170 Participants n=21 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race · Black	24 Participants n=5 Participants	24 Participants n=7 Participants	31 Participants n=5 Participants	16 Participants n=4 Participants	95 Participants n=21 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race · White	23 Participants n=5 Participants	28 Participants n=7 Participants	19 Participants n=5 Participants	8 Participants n=4 Participants	78 Participants n=21 Participants
Race/Ethnicity, Customized Race · Other	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	25 Participants n=5 Participants	21 Participants n=7 Participants	24 Participants n=5 Participants	12 Participants n=4 Participants	82 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	27 Participants n=5 Participants	32 Participants n=7 Participants	28 Participants n=5 Participants	13 Participants n=4 Participants	100 Participants n=21 Participants
Region of Enrollment Puerto Rico	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Region of Enrollment United States	37 Participants n=5 Participants	42 Participants n=7 Participants	37 Participants n=5 Participants	21 Participants n=4 Participants	137 Participants n=21 Participants
Region of Enrollment Dominican Republic	14 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	3 Participants n=4 Participants	37 Participants n=21 Participants
Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA)	4.18 log10 copies/mL STANDARD_DEVIATION 0.672 • n=5 Participants	4.35 log10 copies/mL STANDARD_DEVIATION 0.670 • n=7 Participants	4.33 log10 copies/mL STANDARD_DEVIATION 0.722 • n=5 Participants	4.35 log10 copies/mL STANDARD_DEVIATION 0.780 • n=4 Participants	4.30 log10 copies/mL STANDARD_DEVIATION 0.700 • n=21 Participants
HIV-1 RNA Categories <= 100,000 copies/mL	47 Participants n=5 Participants	44 Participants n=7 Participants	43 Participants n=5 Participants	21 Participants n=4 Participants	155 Participants n=21 Participants
HIV-1 RNA Categories > 100,000 copies/mL	5 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	4 Participants n=4 Participants	27 Participants n=21 Participants
Clusters of Differentiation 4+ (CD4) Cell Count	506 cells/μL STANDARD_DEVIATION 297.0 • n=5 Participants	490 cells/μL STANDARD_DEVIATION 209.9 • n=7 Participants	470 cells/μL STANDARD_DEVIATION 221.7 • n=5 Participants	534 cells/μL STANDARD_DEVIATION 260.0 • n=4 Participants	495 cells/μL STANDARD_DEVIATION 246.5 • n=21 Participants
CD4 Cell Count Categories < 50 cells/μL	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
CD4 Cell Count Categories >= 50 to < 200 cells/μL	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
CD4 Cell Count Categories >= 200 to < 350 cells/μL	17 Participants n=5 Participants	15 Participants n=7 Participants	16 Participants n=5 Participants	4 Participants n=4 Participants	52 Participants n=21 Participants
CD4 Cell Count Categories >= 350 to < 500 cells/μL	17 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	11 Participants n=4 Participants	58 Participants n=21 Participants
CD4 Cell Count Categories >= 500 cells/μL	18 Participants n=5 Participants	22 Participants n=7 Participants	18 Participants n=5 Participants	10 Participants n=4 Participants	68 Participants n=21 Participants
CD4 Percentage (%)	24.2 percentage of CD4 cells STANDARD_DEVIATION 9.92 • n=5 Participants	24.1 percentage of CD4 cells STANDARD_DEVIATION 8.04 • n=7 Participants	22.7 percentage of CD4 cells STANDARD_DEVIATION 8.28 • n=5 Participants	26.2 percentage of CD4 cells STANDARD_DEVIATION 8.18 • n=4 Participants	24.0 percentage of CD4 cells STANDARD_DEVIATION 8.70 • n=21 Participants

PRIMARY outcome

Timeframe: Week 54

Population: Full Analysis Set included all randomized participants who were randomized and received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm	90.4 percentage of participants	84.9 percentage of participants	84.6 percentage of participants	92.0 percentage of participants

SECONDARY outcome

Timeframe: Week 28

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 28 was 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. Week 28 window was between Days 176 and 231 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm	94.2 percentage of participants	92.5 percentage of participants	94.2 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: Week 38

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 38 was 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. Week 38 window was between Days 232 and 322 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm	90.4 percentage of participants	88.7 percentage of participants	88.5 percentage of participants	96.0 percentage of participants

SECONDARY outcome

Timeframe: Week 80

Population: Participants in the Full Analysis Set were analyzed.

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 80 was 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. The Week 80 window was between Days 505 and 595 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm	86.5 percentage of participants	75.5 percentage of participants	86.5 percentage of participants	92 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 28

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=49 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=51 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=50 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in Log10 HIV-1 RNA at Week 28	-2.92 log10 copies/mL Standard Deviation 0.649	-3.04 log10 copies/mL Standard Deviation 0.638	-3.01 log10 copies/mL Standard Deviation 0.716	-3.07 log10 copies/mL Standard Deviation 0.774

SECONDARY outcome

Timeframe: Baseline, Week 38

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=49 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=51 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=47 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in Log10 HIV-1 RNA at Week 38	-2.96 log10 copies/mL Standard Deviation 0.639	-3.06 log10 copies/mL Standard Deviation 0.641	-3.02 log10 copies/mL Standard Deviation 0.771	-3.04 log10 copies/mL Standard Deviation 0.760

SECONDARY outcome

Timeframe: Baseline, Week 54

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=49 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=47 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=47 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=23 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in Log10 HIV-1 RNA at Week 54	-2.95 log10 copies/mL Standard Deviation 0.636	-3.12 log10 copies/mL Standard Deviation 0.589	-2.85 log10 copies/mL Standard Deviation 0.840	-3.08 log10 copies/mL Standard Deviation 0.787

SECONDARY outcome

Timeframe: Baseline, Week 80

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=48 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=42 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=46 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=24 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in Log10 HIV-1 RNA at Week 80	-2.96 log10 Copies/mL Standard Deviation 0.539	-3.08 log10 Copies/mL Standard Deviation 0.592	-2.96 log10 Copies/mL Standard Deviation 0.747	-3.09 log10 Copies/mL Standard Deviation 0.755

SECONDARY outcome

Timeframe: Baseline, Week 28

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=49 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=50 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=50 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28	172 cells/µL Standard Deviation 178.2	158 cells/µL Standard Deviation 164.1	206 cells/µL Standard Deviation 154.6	163 cells/µL Standard Deviation 157.7

SECONDARY outcome

Timeframe: Baseline, Week 38

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=49 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=51 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=46 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in CD4+ Cell Count at Week 38	195 cells/µL Standard Deviation 164.6	220 cells/µL Standard Deviation 187.5	211 cells/µL Standard Deviation 166.2	232 cells/µL Standard Deviation 209.3

SECONDARY outcome

Timeframe: Baseline, Week 54

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=49 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=47 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=47 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=23 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in CD4+ Cell Count at Week 54	204 cells/µL Standard Deviation 189.1	213 cells/µL Standard Deviation 187.2	220 cells/µL Standard Deviation 175.5	193 cells/µL Standard Deviation 191.1

SECONDARY outcome

Timeframe: Baseline, Week 80

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=48 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=41 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=46 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=24 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Change From Baseline in CD4+ Cell Count at Week 80	275 cells/μL Standard Deviation 211.8	262 cells/μL Standard Deviation 184.4	245 cells/μL Standard Deviation 237.4	248 cells/μL Standard Deviation 218.7

SECONDARY outcome

Timeframe: Up to 174.9 weeks

Population: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.

TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	98.1 percentage of participants	88.7 percentage of participants	90.4 percentage of participants	84.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 174.9 weeks

Population: Participants in the Safety Analysis Set were analyzed.

Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last exposure date for participants who permanently discontinued study drug. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF n=52 Participants Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF n=25 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities Grade 3	17.3 percentage of participants	28.3 percentage of participants	30.8 percentage of participants	24.0 percentage of participants
Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities Grade 4	13.5 percentage of participants	9.4 percentage of participants	13.5 percentage of participants	0 percentage of participants
Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities Grade 1	9.6 percentage of participants	3.8 percentage of participants	9.6 percentage of participants	0 percentage of participants
Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities Grade 2	55.8 percentage of participants	56.6 percentage of participants	42.3 percentage of participants	76.0 percentage of participants

SECONDARY outcome

Timeframe: Day 2, 8, Day 1 SC (Day 15), Week 28 and Week 54

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=53 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN Day 2	28.3 ng/mL Standard Deviation 27.15	26.1 ng/mL Standard Deviation 20.46	—	—
Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN Day 8	34.5 ng/mL Standard Deviation 20.96	32.1 ng/mL Standard Deviation 14.71	—	—
Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN Day 1 SC (Day 15)	30.9 ng/mL Standard Deviation 16.76	31.2 ng/mL Standard Deviation 14.66	—	—
Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN Week 28	22.0 ng/mL Standard Deviation 11.70	23.0 ng/mL Standard Deviation 14.81	—	—
Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN Week 54	26.9 ng/mL Standard Deviation 14.19	26.4 ng/mL Standard Deviation 12.10	—	—

SECONDARY outcome

Timeframe: Day 2, 8, 15 , Week 28 and Week 54

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=52 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY Day 2	29.8 ng/mL Standard Deviation 42.70	—	—	—
PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY Day 8	78.7 ng/mL Standard Deviation 55.90	—	—	—
PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY Day 15	97.2 ng/mL Standard Deviation 67.25	—	—	—
PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY Week 28	96.6 ng/mL Standard Deviation 76.40	—	—	—
PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY Week 54	98.4 ng/mL Standard Deviation 85.25	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1

Population: PK Substudy Analysis Set included participants who were randomized into the study, were enrolled into the PK Substudy, had received at least 1 dose of active study drug, and had at least 1 nonmissing intensive PK substudy concentration value for any analyte of interest reported by the PK lab.

AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2) and at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=10 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=14 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 TAF	298.0 hoursnanogram/mL (hng/mL) Standard Deviation 88.0	260.0 hoursnanogram/mL (hng/mL) Standard Deviation 63.5	—	—
PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 TFV	27.1 hoursnanogram/mL (hng/mL) Standard Deviation 27.9	40.5 hoursnanogram/mL (hng/mL) Standard Deviation 59.7	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1

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

Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=10 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=14 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 TAF	278.8 ng/mL Standard Deviation 87.7	318.4 ng/mL Standard Deviation 57.7	—	—
PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 TFV	5.4 ng/mL Standard Deviation 26.5	13.8 ng/mL Standard Deviation 160.2	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1

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

Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=10 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=14 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 TAF	0.50 hours Interval 0.5 to 1.0	0.50 hours Interval 0.5 to 0.5	—	—
PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 TFV	1.50 hours Interval 1.0 to 2.02	1.00 hours Interval 0.5 to 1.17	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1

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

Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK sub study analysis was conducted for Group 1 and 2 on Day 1.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=4 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=9 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1	2.7 ng/mL Standard Deviation 23.1	3.9 ng/mL Standard Deviation 38.0	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 TAF	231.2 h*ng/mL Standard Deviation 60.0	—	—	—
PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 TFV	173.1 h*ng/mL Standard Deviation 52.5	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 TAF	308.7 ng/mL Standard Deviation 74.7	—	—	—
PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 TFV	31.2 ng/mL Standard Deviation 51.7	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 TAF	0.53 hours Interval 0.5 to 1.04	—	—	—
PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 TFV	1.00 hours Interval 1.0 to 2.0	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TFV was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TFV: Clast at Weeks 16, 22, or 28	22.2 ng/mL Standard Deviation 62.6	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=11 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF: AUClast at Week 38	211.5 h*ng/mL Standard Deviation 74.1	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=11 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF: Cmax at Week 38	279.0 ng/mL Standard Deviation 67.8	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=11 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TAF: Tmax at Week 38	0.50 hours Interval 0.5 to 0.5	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 1, 2, and 6 hours postdose

Population: The PBMC PK Substudy Analysis Set included all randomized participants who took at least 1 dose of study drug, participated in the PBMC substudy, and have at least 1 nonmissing postdose concentration value for tenofovir diphosphate (TFV-DP). The PBMC PK Substudy Analysis Set was used for PK analyses of TFV-DP.

AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A peripheral blood mononuclear cell (PBMC) substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=13 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=13 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22	16.2 h*μM Standard Deviation 68.3	21.6 h*μM Standard Deviation 71.9	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 1, 2, and 6 hours postdose

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

Cmax is defined as the maximum observed concentration of drug. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=13 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=13 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22	3.3 micrometer (μM) Standard Deviation 37.5	4.3 micrometer (μM) Standard Deviation 71.8	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 1, 2, and 6 hours postdose

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

Tmax is defined as the time (observed time point) of Cmax. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits.

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=13 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) n=13 Participants Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22	2.00 hours Interval 1.0 to 6.0	6.00 hours Interval 1.0 to 6.0	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=11 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of Bictegravir (BIC): AUClast at Week 38	72865.9 h*ng/mL Standard Deviation 31.0	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of BIC: Cmax at Week 38	10180.0 ng/mL Standard Deviation 42.8	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of BIC: Tmax at Week 38	2.00 hours Interval 1.0 to 3.0	—	—	—

SECONDARY outcome

Timeframe: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

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

Outcome measures

Outcome measures
Measure	Group 1: SC LEN+(F/TAF→ TAF) n=12 Participants Induction phase: Participants received lenacapavir (LEN) 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus emtricitabine/ tenofovir alafenamide (F/TAF) (200/25 mg) fixed-dose combination (FDC) tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via subcutaneous (SC) injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus TAF 25 mg tablets once daily orally at Week 28 and will continue up to Week 80. Participants willing to continue the study beyond Week 80 will continue to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily TAF 25 mg tablets from Week 80 onwards.	Group 2: SC LEN + (F/TAF → BIC) Induction phase: Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 300 mg tablet orally on Day 8 plus F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 to Week 28 plus LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Day 15. Maintenance phase: Participants received LEN 927 mg (309 mg/mL; 2 X 1.5 mL) via SC injection on Week 28 and every 6 months (26 weeks) thereafter plus bictegravir (BIC) 75 mg tablets once daily orally at Week 28 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive SC LEN 927 mg injection every 6 months (26 weeks) and oral daily BIC 75 mg tablets from Week 80 onwards.	Group 3: Oral LEN + F/TAF Participants received LEN 600 mg (2 X 300 mg, tablet) orally on Days 1 and 2, followed by LEN 50 mg tablets once daily orally from Day 3 and continued up to Week 80. Participants received F/TAF (200/25 mg) FDC tablets once daily orally from Day 1 and continued up to Week 80. Participants willing to continue the study beyond Week 80 continued to receive oral daily LEN 50 mg tablets and oral daily F/TAF 200/25 mg FDC tablets from Week 80 onwards.	Group 4: B/F/TAF Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablets once daily orally from Day 1 and throughout their participation in the study up to Week 80.
PK of BIC: Clast at Week 38	8474.5 ng/mL Standard Deviation 33.3	—	—	—

Adverse Events

Group 1: SC LEN+(F/TAF→ TAF)

Serious events: 4 serious events

Other events: 47 other events

Deaths: 1 deaths

Group 2: SC LEN + (F/TAF → BIC)

Serious events: 4 serious events

Other events: 46 other events

Deaths: 0 deaths

Group 3: Oral LEN + F/TAF

Serious events: 7 serious events

Other events: 42 other events

Deaths: 1 deaths

Group 4: B/F/TAF

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 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