Trial Outcomes & Findings for Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV (NCT NCT05052996)

Results Overview

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 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 the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

142 participants

Primary outcome timeframe

Week 24

Results posted on

2026-02-04

Participant Flow

Participants were enrolled at study sites in the United States. This is the primary results analysis including data up to Week 48 for the outcome measures. As Cohort 1 never reached Week 48, so, the data for some outcome measures for applicable timepoints up to Week 48 were reported for Cohort 2 only.

322 participants were screened.

Participant milestones

Participant milestones
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Overall Study STARTED	24	12	53	53
Overall Study COMPLETED	0	0	2	4
Overall Study NOT COMPLETED	24	12	51	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Overall Study Still on study	0	0	47	44
Overall Study Cohort terminated by sponsor	21	12	0	0
Overall Study Withdrew consent	1	0	1	2
Overall Study Lost to Follow-up	1	0	0	2
Overall Study Adverse Event	0	0	2	0
Overall Study Randomized but never treated	0	0	1	1
Overall Study Protocol Violation	1	0	0	0

Baseline Characteristics

Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1- Group 1 (ISL+LEN) n=24 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) n=12 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Total n=140 Participants Total of all reporting groups
Race/Ethnicity, Customized Other or More Than One Race	1 Participants n=25 Participants	0 Participants n=26 Participants	3 Participants n=51 Participants	5 Participants n=8 Participants	9 Participants n=23 Participants
Race/Ethnicity, Customized Asian	0 Participants n=25 Participants	1 Participants n=26 Participants	2 Participants n=51 Participants	1 Participants n=8 Participants	4 Participants n=23 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=25 Participants	0 Participants n=26 Participants	1 Participants n=51 Participants	2 Participants n=8 Participants	3 Participants n=23 Participants
Age, Categorical <=18 years	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants	0 Participants n=8 Participants	0 Participants n=23 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=25 Participants	12 Participants n=26 Participants	50 Participants n=51 Participants	46 Participants n=8 Participants	130 Participants n=23 Participants
Age, Categorical >=65 years	2 Participants n=25 Participants	0 Participants n=26 Participants	2 Participants n=51 Participants	6 Participants n=8 Participants	10 Participants n=23 Participants
Age, Continuous	42 years STANDARD_DEVIATION 11.9 • n=25 Participants	40 years STANDARD_DEVIATION 11.2 • n=26 Participants	43 years STANDARD_DEVIATION 12.1 • n=51 Participants	45 years STANDARD_DEVIATION 13.3 • n=8 Participants	43 years STANDARD_DEVIATION 12.4 • n=23 Participants
Sex: Female, Male Female	2 Participants n=25 Participants	1 Participants n=26 Participants	10 Participants n=51 Participants	9 Participants n=8 Participants	22 Participants n=23 Participants
Sex: Female, Male Male	22 Participants n=25 Participants	11 Participants n=26 Participants	42 Participants n=51 Participants	43 Participants n=8 Participants	118 Participants n=23 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=25 Participants	4 Participants n=26 Participants	13 Participants n=51 Participants	17 Participants n=8 Participants	41 Participants n=23 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=25 Participants	8 Participants n=26 Participants	39 Participants n=51 Participants	35 Participants n=8 Participants	99 Participants n=23 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants	0 Participants n=8 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized White	10 Participants n=25 Participants	6 Participants n=26 Participants	25 Participants n=51 Participants	27 Participants n=8 Participants	68 Participants n=23 Participants
Race/Ethnicity, Customized Black or African American	13 Participants n=25 Participants	5 Participants n=26 Participants	21 Participants n=51 Participants	16 Participants n=8 Participants	55 Participants n=23 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants	1 Participants n=8 Participants	1 Participants n=23 Participants
Region of Enrollment United States	24 Participants n=25 Participants	12 Participants n=26 Participants	52 Participants n=51 Participants	52 Participants n=8 Participants	140 Participants n=23 Participants

PRIMARY outcome

Timeframe: Week 24

Population: The Full Analysis Set included all randomized participants who took at least 1 dose of study drug. As none of the participants reached Week 24 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 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 the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm	—	—	1.9 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: The participants in the Full Analysis Set were analyzed. As none of the participants were on-treatment in Cohort 1 at Week 12 (required for the analysis of HIV RNA levels using US FDA-defined Snapshot Algorithm), this outcome measure for Cohort 1 could not be analyzed using US FDA-defined Snapshot Algorithm.

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 12 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 the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm	—	—	1.9 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: The participants in the Full Analysis Set were analyzed. As none of the participants reached Week 48 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 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 the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	—	—	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: The participants in the Full Analysis Set were analyzed. As none of the participants were on-treatment in Cohort 1 at Week 12 (required for the analysis of HIV RNA levels using US FDA-defined Snapshot Algorithm), this outcome measure for Cohort 1 could not be analyzed using US FDA-defined Snapshot Algorithm.

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 12 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 the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm	—	—	98.1 percentage of participants Interval 89.7 to 100.0	96.2 percentage of participants Interval 86.8 to 99.5

SECONDARY outcome

Timeframe: Week 24

Population: The participants in the Full Analysis Set were analyzed. As none of the participants reached Week 24 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 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 the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm	—	—	94.2 percentage of participants Interval 84.1 to 98.8	96.2 percentage of participants Interval 86.8 to 99.5

SECONDARY outcome

Timeframe: Week 48

Population: The participants in the Full Analysis Set were analyzed. As none of the participants reached Week 48 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 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 the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	—	—	96.2 percentage of participants Interval 86.8 to 99.5	94.2 percentage of participants Interval 84.1 to 98.8

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The participants from the Safety Analysis Set with available data were analyzed.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=24 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) n=12 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 Baseline	721 cells/µL Standard Deviation 265.0	659 cells/µL Standard Deviation 304.8	755 cells/µL Standard Deviation 223.6	818 cells/µL Standard Deviation 271.3
Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 Change at Week 12	-50 cells/µL Standard Deviation 183.0	18 cells/µL Standard Deviation 142.3	-23 cells/µL Standard Deviation 185.6	-49 cells/µL Standard Deviation 180.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The participants in the Safety Analysis Set with available data were analyzed. As none of the participants reached Week 24 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=50 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=50 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Change From Baseline in CD4+ Cell Count at Week 24	—	—	-4 cells/µL Standard Deviation 182.1	-57 cells/µL Standard Deviation 204.2

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: The participants in the Safety Analysis Set with available data were analyzed. As none of the participants reached Week 48 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=50 Participants Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=49 Participants Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Change From Baseline in CD4+ Cell Count at Week 48	—	—	-12 cells/µL Standard Deviation 214.7	-29 cells/µL Standard Deviation 186.1

SECONDARY outcome

Timeframe: Up to 5 years

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 data not reported

SECONDARY outcome

Timeframe: Anytime postdose at Week 4

Population: The Pharmacokinetic (PK) Analysis Set for Cohort 1 included all randomized participants who took at least 1 dose of study drug and have at least 1 nonmissing concentration value reported by the PK laboratory.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=23 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 1: Plasma Concentrations for ISL	42.1 ng/mL Standard Deviation 49.6	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose on Day 1 and at either Week 12 or Week 18

Population: The Pharmacokinetic (PK) Substudy Analysis Set for Cohort 2 included all randomized participants who received at least 1 dose of the study drug, participated in the PK substudy, and had at least 1 nonmissing postdose concentration with available data were analyzed.

Cmax was defined as the maximum observed concentration of drug.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=14 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) Day 1	19.6 ng/mL Standard Deviation 6.55	—	—	—
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) Week 12 or Week 18	18.7 ng/mL Standard Deviation 7.6	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose on Day 1 and at either Week 12 or Week 18

Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.

Tmax was defined as the time (observed time point) of Cmax.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=14 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: PK Parameter: Tmax of ISL Day 1	1.12 hours Standard Deviation 1.03	—	—	—
Cohort 2: PK Parameter: Tmax of ISL Week 12 or Week 18	0.793 hours Standard Deviation 0.423	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose at either Week 12 or Week 18

Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 were analyzed.

Ctau was defined as the observed drug concentration at the end of the dosing interval.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=14 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: PK Parameter: Ctau of ISL	0.169 ng/mL Standard Deviation 0.0940	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose at either Week 12 or Week 18

Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 were analyzed.

AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=14 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: PK Parameter: AUCtau of ISL	132 h*ng/mL Standard Deviation 98.1	—	—	—

SECONDARY outcome

Timeframe: Anytime postdose at Week 4

Population: The participants in the Pharmacokinetic Analysis Set for Cohort 1 were analyzed.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=24 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Plasma Concentrations for LEN	62.0 ng/mL Standard Deviation 43.9	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose on Day 1, Day 2 and at either Week 12 or 18

Population: The participants in Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.

Cmax was defined as the maximum observed concentration of drug.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=14 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN Day 1	46.4 ng/mL Standard Deviation 29.0	—	—	—
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN Day 2	183 ng/mL Standard Deviation 189	—	—	—
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN Week 12 or Week 18	97.4 ng/mL Standard Deviation 73.2	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18

Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.

Tmax is defined as the time (observed time point) of Cmax.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=14 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: PK Parameter: Tmax of LEN Day 1	11.4 hours Standard Deviation 8.96	—	—	—
Cohort 2: PK Parameter: Tmax of LEN Day 2	6.61 hours Standard Deviation 1.47	—	—	—
Cohort 2: PK Parameter: Tmax of LEN Week 12 or Week 18	5.43 hours Standard Deviation 1.63	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose at either Week 12 or Week 18

Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.

Ctau was defined as the observed drug concentration at the end of the dosing interval.

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=12 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: PK Parameter: Ctau of LEN	36.6 ng/mL Standard Deviation 22.5	—	—	—

SECONDARY outcome

Timeframe: Anytime post dose at either Week 12 or Week 18

Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.

AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Outcome measures

Outcome measures
Measure	Cohort 1- Group 1 (ISL+LEN) n=12 Participants Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Cohort 2: PK Parameter: AUCtau of LEN	10000 h*ng/mL Standard Deviation 7440	—	—	—

Adverse Events

Cohort 1- Group 1 (ISL+LEN)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Cohort 1- Group 2 (B/F/TAF to ISL+LEN)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort 2- Group 1 (ISL+LEN)

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Cohort2- Group 2 (B/F/TAF to ISL+LEN)

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1- Group 1 (ISL+LEN) n=24 participants at risk Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 1- Group 2 (B/F/TAF to ISL+LEN) n=12 participants at risk Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study.	Cohort 2- Group 1 (ISL+LEN) n=52 participants at risk Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.	Cohort2- Group 2 (B/F/TAF to ISL+LEN) n=52 participants at risk Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks.
Gastrointestinal disorders Large intestine perforation	0.00% 0/24 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	1.9% 1/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Infections and infestations Pneumonia	0.00% 0/24 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	1.9% 1/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Injury, poisoning and procedural complications Anaesthetic complication neurological	0.00% 0/24 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	1.9% 1/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Renal and urinary disorders Renal colic	0.00% 0/24 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/12 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	1.9% 1/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.	0.00% 0/52 • All-Cause Mortality: Cohort 1: Up to Week 12; Cohort 2: Up to Week 74.6. Adverse Events: Cohort 1: Up to Week 12; Cohort 2: Up to Week 48 All-cause mortality: All Randomized Analysis Set included all participants who were randomized in the study. Adverse events: Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.

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