Study Evaluating the Safety and Efficacy of Islatravir in... | NCT05052996

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1 (ISL+LEN)	Experimental	Participants will receive the following for at least 48 weeks: Day 1 and Day 2: ISL 40 and LEN 600 mg Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg	Drug: ISL Drug: LEN
Cohort 1 (B/F/TAF to ISL+LEN)	Experimental	Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN ISL 40 and LEN 600 mg on Day 1 and Day 2 ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.	Drug: ISL Drug: LEN Drug: B/F/TAF
Cohort 2 (ISL+LEN)	Experimental	Participants will receive the following for at least 48 weeks Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) Day 2: LEN only oral 600 mg (2 x 300 mg) Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg	Drug: ISL Drug: LEN
Cohort 2 (B/F/TAF to ISL+LEN)	Experimental	Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.	Drug: ISL Drug: LEN Drug: B/F/TAF
Extension Phase Cohort 2 of ISL/LEN Fixed Dose Combination (FDC)

Name	Type	Description	Arm Group Labels	Other Names
ISL	Drug	Capsules administered orally without regard to food	Cohort 1 (B/F/TAF to ISL+LEN) Cohort 1 (ISL+LEN) Cohort 2 (B/F/TAF to ISL+LEN)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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.	Week 24

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the 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.

Eligibility Module

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pacific Oaks Medical Group		Beverly Hills	California	90211	United States
Ruane Clinical Research Group, Inc

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41429026	Derived	Colson AE, Crofoot GE, Ruane PJ, Ramgopal MN, Dretler AW, Nahass RG, Sinclair GI, Berhe M, Roberts A, Applin S, Brinson C, Jayaweera D, Workowski KA, Shihadeh F, Liu SY, Klopfer S, Llamoso C, Madera S, Dvory-Sobol H, Rhee MS, Rhee EG, Baeten JM, Eron JJ. Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study. Ann Intern Med. 2026 Feb;179(2):168-176. doi: 10.7326/ANNALS-25-01939. Epub 2025 Dec 23.

Label	URL
Gilead Clinical Trials Website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Protocol Amendment 6	Dec 2, 2025

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00042± 11.9 BG00140± 11.2 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG0014 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG00010 BG0016 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00024 BG00112 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

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.

Posted

Number

percentage of participants

Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Units	Counts
Participants	OG0000 OG0010 OG00252 OG003

Title

Denominators

Categories

Title	Measurements
	OG0021.9 OG0030

Secondary

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the 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.

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.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

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.

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.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the 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.

Posted

Number

95% Confidence Interval

percentage of participants

Week 12

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12

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

Posted

Mean

Standard Deviation

cells/µL

Baseline and Week 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Cohort2- Group 2 (B/F/TAF to ISL+LEN)

Secondary

Change From Baseline in CD4+ Cell Count at Week 24

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.

Posted

Mean

Standard Deviation

cells/µL

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Change From Baseline in CD4+ Cell Count at Week 48

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.

Posted

Mean

Standard Deviation

cells/µL

Baseline and Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation

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.

Not Posted

Up to 5 years

Participants

Secondary

Cohort 1: Plasma Concentrations for ISL

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.

Posted

Mean

Standard Deviation

ng/mL

Anytime postdose at Week 4

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL)

Cmax was defined as the maximum observed concentration of drug.

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.

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Cohort 2: PK Parameter: Tmax of ISL

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

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

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Cohort 2: PK Parameter: Ctau of ISL

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

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

Posted

Mean

Standard Deviation

ng/mL

Anytime post dose at either Week 12 or Week 18

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG00014

Secondary

Cohort 2: PK Parameter: AUCtau of ISL

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

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

Posted

Mean

Standard Deviation

h*ng/mL

Anytime post dose at either Week 12 or Week 18

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Plasma Concentrations for LEN

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

Posted

Mean

Standard Deviation

ng/mL

Anytime postdose at Week 4

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG00024

Secondary

Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN

Cmax was defined as the maximum observed concentration of drug.

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

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Cohort 2: PK Parameter: Tmax of LEN

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

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

Posted

Mean

Standard Deviation

hours

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Cohort 2: PK Parameter: Ctau of LEN

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

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

Posted

Mean

Standard Deviation

ng/mL

Anytime post dose at either Week 12 or Week 18

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Cohort 2: PK Parameter: AUCtau of LEN

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

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

Posted

Mean

Standard Deviation

h*ng/mL

Anytime post dose at either Week 12 or Week 18

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	24	0	24	11	24
EG001	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.	12	0	12	7	12
EG002	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.	53	3	52	27	52
EG003	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.	53	0	52	29	52

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Large intestine perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG0030 affected52 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG003
Anaesthetic complication neurological	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0026 affected52 at risk EG0033 affected52 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0020 affected52 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected24 at risk EG0010 affected12 at risk EG0023 affected52 at risk EG003
Fatigue	General disorders and administration site conditions	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0024 affected52 at risk EG003
Anal chlamydia infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0023 affected52 at risk EG003
Covid-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0007 affected24 at risk EG0012 affected12 at risk EG0026 affected52 at risk EG003
Folliculitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 affected24 at risk EG0011 affected12 at risk EG0022 affected52 at risk EG003
Sinusitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 affected24 at risk EG0011 affected12 at risk EG0021 affected52 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 affected24 at risk EG0010 affected12 at risk EG0027 affected52 at risk EG003
Exposure to communicable disease	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0020 affected52 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0011 affected12 at risk EG0020 affected52 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0011 affected12 at risk EG0020 affected52 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected24 at risk EG0010 affected12 at risk EG0023 affected52 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0012 affected12 at risk EG0023 affected52 at risk EG003
Sinus headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0011 affected12 at risk EG0020 affected52 at risk EG003
Taste disorder	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0011 affected12 at risk EG0021 affected52 at risk EG003
Depression	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0011 affected12 at risk EG0020 affected52 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0020 affected52 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected24 at risk EG0010 affected12 at risk EG0021 affected52 at risk EG003

ID	Term
C000730993	lenacapavir
C000654125	bictegravir, emtricitabine, tenofovir alafenamide, drug combination